@article{liu_paudel_flowers_piedrahita_wang_2023, title={Adrenomedullin Stimulates Proliferation, Migration and Adhesion of Porcine Trophectoderm Cells Via CALCRL-AKT-TSC2-MTORC1 Cell Signaling Pathway}, volume={101}, ISSN={["1525-3163"]}, DOI={10.1093/jas/skad068.040}, abstractNote={Abstract}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Liu, Bangmin and Paudel, Sudikshya and Flowers, William L. and Piedrahita, Jorge A. and Wang, Xiaoqiu}, year={2023}, month={May} }
 @article{jenkins_flowers_2023, title={Biological and Management Factors Affecting Colostrum Intake and Pre-Weaning Survival in Piglets}, volume={101}, ISSN={["1525-3163"]}, DOI={10.1093/jas/skad341.033}, abstractNote={Abstract}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Jenkins, Abigail K. and Flowers, William L.}, year={2023}, month={Oct}, pages={29–30} }
 @article{liu_paudel_flowers_piedrahita_wang_2023, title={Uterine histotroph and conceptus development: III. Adrenomedullin stimulates proliferation, migration and adhesion of porcine trophectoderm cells via AKT-TSC2-MTOR cell signaling pathway}, volume={4}, ISSN={["1438-2199"]}, DOI={10.1007/s00726-023-03265-6}, abstractNote={Adrenomedullin (ADM) as a highly conserved peptide hormone has been reported to increase significantly in the uterine lumen during the peri-implantation period of pregnancy in pigs, but its functional roles in growth and development of porcine conceptus (embryonic/fetus and its extra-embryonic membranes) as well as underlying mechanisms remain largely unknown. Therefore, we conducted in vitro experiments using our established porcine trophectoderm cell line (pTr2) isolated from Day-12 porcine conceptuses to test the hypothesis that porcine ADM stimulates cell proliferation, migration and adhesion via activation of mechanistic target of rapamycin (MTOR) cell signaling pathway in pTr2 cells. Porcine ADM at 10–7 M stimulated (P < 0.05) pTr2 cell proliferation, migration and adhesion by 1.4-, 1.5- and 1.2-folds, respectively. These ADM-induced effects were abrogated (P < 0.05) by siRNA-mediated knockdown of ADM (siADM) and its shared receptor component calcitonin-receptor-like receptor (CALCRL; siCALCRL), as well as by rapamycin, the inhibitor of MTOR. Using siRNA-mediated knockdown of CALCRL coupled with Western blot analyses, ADM signaling transduction was determined in which ADM binds to CALCRL to increase phosphorylation of MTOR, its downstream effectors (4EBP1, P70S6K, and S6), and upstream regulators (AKT and TSC2). Collectively, these results suggest that porcine ADM in histotroph acts on its receptor component CALCRL to activate AKT-TSC2-MTOR, particularly MTORC1 signaling cascade, leading to elongation, migration and attachment of conceptuses.}, journal={AMINO ACIDS}, author={Liu, Bangmin and Paudel, Sudikshya and Flowers, William L. and Piedrahita, Jorge A. and Wang, Xiaoqiu}, year={2023}, month={Apr} }
 @article{flowers_2022, title={Factors affecting the production of quality ejaculates from boars}, volume={246}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2021.106840}, abstractNote={Production of acceptable quality ejaculates in boars is dependent upon the Sertoli cell population established before puberty and how effectively these cells function after sexual maturity. In general, factors affecting Sertoli cell mitosis tend to have a two-fold greater effect on sperm production compared with those affecting spermatogenesis. Birthweight is a reliable indicator of in utero testicular development and prepubertal growth rates are positively correlated with testis size and sperm production after sexual maturity. Colostrum intake and pre-weaning nutrition account for much of the variation associated with quality and quantity of ejaculates and represent opportunities to further enhance lifetime sperm production. Interactions between young boars and humans, shortly after weaning, have important effects on spermatogenesis after sexual maturity and need to be studied further. The seasonal effect on depression in semen quality is the most significant factor affecting production of acceptable quality ejaculates after puberty. Ambient temperatures, greater than those of the thermoneutral zone, have both acute and chronic effects that compromise all aspects of the male reproductive axis. Identification of genes associated with heat-tolerant phenotypes holds promise for addressing this challenge, especially in light of the current trend in global warming. Supplementation of vitamins, minerals and other compounds have positive effects on sperm production during periods in which other stressors, especially heat stress, are present and is an important mitigation strategy. Recent information on housing conditions and boar usage patterns indicate these cause relatively minor changes in sperm production, overall, but for some males can have significant, long-term effects.}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Flowers, W. L.}, year={2022}, month={Nov} }
 @article{flowers_2022, title={Litter-of-origin traits and their association with lifetime productivity in sows and boars}, ISSN={["1098-2795"]}, DOI={10.1002/mrd.23565}, abstractNote={Abstract}, journal={MOLECULAR REPRODUCTION AND DEVELOPMENT}, author={Flowers, William L.}, year={2022}, month={Mar} }
 @article{lents_supakorn_dedecker_phillips_boyd_vallet_rohrer_foxcroft_flowers_trottier_et al._2020, title={Dietary lysine-to-energy ratios for managing growth and pubertal development in replacement gilts}, volume={36}, ISSN={["2590-2865"]}, DOI={10.15232/aas.2020-02016}, abstractNote={ABSTRACT Objective Our objectives were to determine growth rates, body composition, and pubertal development in replacement gilts fed diets with different ratios of standardized ileal digestible (SID) lysine to ME. Materials and Methods Diets with low, medium, and high ratios of SID lysine to ME (grower: 2.3, 2.6, and 2.8; finisher; 1.7, 1.9, and 2.1 g/Mcal) were fed from 100 to 200 d of age, after which gilts were moved from the gilt development unit to sow farms. Boar exposure and estrus detection began at 160 d of age and continued until first detected estrus. Estimates of BW and body composition were determined at 100, 142, 160, and 200 d of age and at puberty. Results and Discussion Body weights and growth rates were reduced (P Implications and Applications Reducing SID lysine–to–ME ratios in gilt diets can increase the number of gilts within optimal BW range at first estrus, but overall pubertal development is delayed if ratios are reduced below 2.8 and 2.1 g of SID lysine to megacalorie of ME in grower and finisher diets, respectively.}, number={5}, journal={APPLIED ANIMAL SCIENCE}, author={Lents, C. A. and Supakorn, C. and DeDecker, A. E. and Phillips, C. E. and Boyd, R. D. and Vallet, J. L. and Rohrer, G. A. and Foxcroft, G. R. and Flowers, W. L. and Trottier, N. L. and et al.}, year={2020}, month={Oct}, pages={701–714} }
 @article{clemons_flowers_2020, title={Effects of birth characteristics, nursing behaviors, and supplemental milk on piglet pre-weaning growth and survival}, volume={98}, ISSN={["1525-3163"]}, DOI={10.1093/jas/skaa054.370}, abstractNote={Abstract}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Clemons, Courtney Moore and Flowers, William}, year={2020}, month={Nov}, pages={213–213} }
 @article{flowers_2020, title={Reproductive management of swine}, ISBN={["978-0-12-817052-6"]}, DOI={10.1016/B978-0-12-817052-6.00016-1}, abstractNote={Swine reproductive management is a multifaceted discipline that has both developmental and functional components. The biggest challenge for replacement boars and sows during the developmental phase is the establishment of physiological benchmarks that are correlated with their adult reproductive performance. Birthweight and weaning weights appear to have strong positive relationship lifetime sperm and piglet production in boars and sows, respectively. Their refinement and use in selection programs should be enthusiastically pursued. Delaying training for semen collection towards the end of their pubertal development appears to be beneficial for lifetime productivity in boars while inducing puberty early and breeding at subsequent estrous periods is positively correlated with adult reproductive performance in gilts. The primary emphasis for both during the functional phase is creating management conditions that minimize their exposure to environmental stressors. A working knowledge of the physiology associated with spermatogenesis and the establishment and maintenance of pregnancy is absolutely critical for this process. The importance of colostrum in the development of both male and female reproductive organs; identification of sperm characteristics that have a quantitative relationship with boar fertility; and use of nutritional programming to enhance embryonic and fetal development in sows are areas of future research that hold potential for further enhancements in reproductive efficiency for the swine industry.}, journal={ANIMAL AGRICULTURE: SUSTAINABILITY, CHALLENGES AND INNOVATIONS}, author={Flowers, William L.}, year={2020}, pages={283–297} }
 @article{dillard_flowers_2020, title={Reproductive performance of sows associated with single, fixed-time insemination programs in commercial farms based on either average herd weaning-to-estrus intervals or postweaning estrous activity}, volume={36}, ISSN={["2590-2865"]}, DOI={10.15232/aas.2019-01913}, abstractNote={ABSTRACT Objective Three separate studies were conducted to determine the effectiveness of adjusting the timing of triptorelin (Ovugel, United Animal Health, Sheridan, IN) administration based on historical weaning-to-estrus intervals (Exp. 1), the occurrence of proestrus (Exp. 2), or the occurrence of estrus (Exp. 3) on reproductive performance of weaned sows. Materials and Methods All studies were conducted on commercial farms in eastern North Carolina during the summer months when both the length and variation associated with weaning-to-estrus intervals for sows were increased. In Exp. 1, sows were assigned at weaning to receive triptorelin at either 96 ± 6 h (n = 196) or 120 ± 6 h (n = 196) followed by a single insemination 22 ± 2 h later. Sows bred once each day of estrus (n = 398) served as the control treatment. In Exp. 2, sows were given boar exposure beginning on d 3 after weaning and at proestrus were assigned to 1 of 2 treatments: (1) control (n = 301), which were bred once each day of detected estrus, or (2) triptorelin (n = 296) followed by a single insemination 22 ± 2 h later. In Exp. 3, sows were given boar exposure beginning on d 3 after weaning, and those detected in estrus on d 4 or 5 were assigned to be bred once each day of estrus (control d 4, n = 98 and control d 5, n = 118) or treated with triptorelin (d 4, n = 97 and d 5, n = 117) followed by a single insemination 22 ± 2 h later. Results and Discussion Reproductive performance was significantly reduced (P ≤ 0.05) when triptorelin was given at a fixed time after weaning irrespective of estrous status compared with the control sows that were bred once each day of estrus (Exp. 1). This was due to the subset of treated sows that were not in estrus when they were bred. In contrast, weaned sows treated with triptorelin at either proestrus or estrus and bred once 22 ± 2 h later had similar reproductive performance (P ≥ 0.63) compared with their counterparts bred once each day of estrus. Implications and Applications Use of either proestrus or estrus as the criterion for intravaginal administration of triptorelin and the subsequent fixed-time AI in herds with extended or variable weaning-to-estrus intervals was effective in terms of maintaining reproductive performance equivalent to conventional AI strategies.}, number={1}, journal={APPLIED ANIMAL SCIENCE}, author={Dillard, D. S. and Flowers, W. L.}, year={2020}, month={Feb}, pages={100–107} }
 @article{he_maltecca_tiezzi_soto_flowers_2020, title={Transcriptome analysis identifies genes and co-expression networks underlying heat tolerance in pigs}, volume={21}, ISSN={["1471-2156"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85083872520&partnerID=MN8TOARS}, DOI={10.1186/s12863-020-00852-4}, abstractNote={Abstract}, number={1}, journal={BMC GENETICS}, author={He, Yuqing and Maltecca, Christian and Tiezzi, Francesco and Soto, Emmanuel Lozada and Flowers, William L.}, year={2020}, month={Apr} }
 @article{knox_stewart_flowers_swanson_webel_kraeling_2018, title={Design and biological effects of a vaginally administered gel containing the GnRH agonist, triptorelin, for synchronizing ovulation in swine}, volume={112}, ISSN={["1879-3231"]}, DOI={10.1016/j.theriogenology.2017.08.021}, abstractNote={A novel gel formulation was selected for intravaginal delivery of the GnRH agonist (triptorelin) for synchronizing ovulation in pigs. Studies with gilt models were used to assess LH response profiles. The lowest dose of triptorelin that induced the most gilts to show an LH surge was 100 μg in 1.2% methylcellulose gel. This formulation had a similar effect in weaned sows while also advancing ovulation. The timing of administration was evaluated in sows after weaning. Administration at 96 h induced more sows to ovulate (58%) by 48 h compared to treatment at estrus (45%) or for controls (34%), but the desired level of ovulation synchrony was not achieved. As a result, greater doses of triptorelin were tested and 200 μg given at 96 h after weaning, induced 81% of sows to ovulate within 48 h after treatment. The best synchrony of ovulation occurred when given at 96 h after weaning compared to earlier or later intervals. The optimum time to give a single fixed time AI (SFT-AI) after administration of 200 μg of triptorelin in 1.2% gel (OvuGel®) at 96 h after weaning was tested. A SFT-AI at 22 ± 2 h after OvuGel achieved the highest fertility and was practical for staff during the normal work day. In field trials, a SFT-AI 22 ± 2 h after all weaned sows were treated with OvuGel improved (P = 0.04) farrowing rate to 82.5% compared to control sows weaned (80.1%), with no effect on numbers of pigs born alive (12.1). Research continues for identifying the advantages for use of OvuGel in different production systems, and potential application for use in gilts.}, journal={THERIOGENOLOGY}, author={Knox, R. V. and Stewart, K. R. and Flowers, W. L. and Swanson, M. E. and Webel, S. K. and Kraeling, R. R.}, year={2018}, month={May}, pages={44–52} }
 @article{chung_zhang_collins_sper_gleason_simpson_koh_sommer_flowers_petters_et al._2018, title={High mobility group A2 (HMGA2) deficiency in pigs leads to dwarfism, abnormal fetal resource allocation, and cryptorchidism}, volume={115}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1721630115}, DOI={10.1073/pnas.1721630115}, abstractNote={Significance}, number={21}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chung, Jaewook and Zhang, Xia and Collins, Bruce and Sper, Renan B. and Gleason, Katherine and Simpson, Sean and Koh, Sehwon and Sommer, Jeffrey and Flowers, William L. and Petters, Robert M. and et al.}, year={2018}, month={May}, pages={5420–5425} }
 @article{lima_lin_jacobi_man_sommer_flowers_blikslager_gonzalez_odle_2017, title={Supplementation of Maternal Diets with Docosahexaenoic Acid and Methylating Vitamins Impacts Growth and Development of Fetuses from Malnourished Gilts}, volume={2}, ISSN={2475-2991}, url={http://dx.doi.org/10.3945/cdn.117.001958}, DOI={10.3945/cdn.117.001958}, abstractNote={Abstract Background Like many species, pregnant swine mobilize and repartition body nutrient stores during extreme malnutrition to support fetal development. Objective The objective of this study was to model chronic human maternal malnutrition and measure effects of methylating-vitamins (MVs, containing choline, folate, B-6, B-12, and riboflavin) and docosahexaenoic acid (DHA) supplementation on fetal growth and development. Methods Pregnant gilts (n = 24) were either fully nourished (2.0 kg/d) with a corn-plus-isolated-soy-protein basal diet (control) supplemented with MVs and DHA or nourishment was restricted throughout gestation. Basal diet fed to malnourished gilts was reduced progressively from 50% to 70% restriction (1.0 to 0.6 kg/d) and was supplemented following a 2 (±MVs) x 2 (±DHA) factorial design. Full-term c-sections were performed to assess impacts on low and normal birth weight (LBW/NBW) fetuses (n = 238). Results Body weight gain of malnourished gilts was 10% of full-fed control dams (P < 0.05), but offspring birth weight, length, girth, and percentage of LBW fetuses were not different between treatments. The number of pigs per litter was reduced by 30% in malnourished control dams. Fetal brain weights were reduced by 7% compared to positive controls (P < 0.05). Micronutrient supplementation to malnourished dams increased fetal brain weights back to full-fed control levels. Dams with DHA produced offspring with higher DHA concentrations in brain and liver (P < 0.05). Plasma choline concentration was 4-fold higher in fetuses from unsupplemented malnourished dams (P < 0.0001). Global DNA methylation status of fetuses from restricted dams was higher than in control fetuses, including brain, liver, heart, muscle, and placenta tissues (P < 0.05). Addition of DHA increased methylation in LBW fetal brains (P < 0.05). Conclusions Despite the mobilization of maternal stores, malnourished litters displayed reduced brain development that was fully mitigated by micronutrient supplementation. Severe maternal malnutrition increased global DNA methylation in several fetal tissues that was unaltered by choline and B-vitamin supplementation.}, number={3}, journal={Current Developments in Nutrition}, publisher={Oxford University Press (OUP)}, author={Lima, Hope K and Lin, Xi and Jacobi, Sheila K and Man, Caolai and Sommer, Jeffrey and Flowers, William and Blikslager, Anthony and Gonzalez, Liara and Odle, Jack}, year={2017}, month={Dec} }
 @article{flowers_deller_stewart_2016, title={Use of heterospermic inseminations and paternity testing to evaluate the relative contributions of common sperm traits and seminal plasma proteins in boar fertility}, volume={174}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2016.09.016}, abstractNote={The objective of this study was to evaluate relationships between common semen quality estimates including sperm motility, sperm morphology, spontaneous capacitation status and seminal plasma proteins and boar fertility using heterospermic inseminations and subsequent paternity testing. All boars (n = 12) used in the study had excellent semen quality (≥70% normal sperm) that resulted in average farrowing rates and litter sizes of 88.9 ± 0.7% and 11.7 ± 0.1 pigs, respectively. Their ejaculates were combined to make heterospermic insemination doses in such a way that each boar was tested against all of his contemporaries. The proportion of piglets sired by each individual was used to separate boars into three fertility groups: High (71.6 ± 4.8%; n = 3); Medium (51.6 ± 3.8%; n = 6); and Low (25.2% ± 5.3%; n = 3). Ejaculates from High fertility boars had more motile sperm with normal acrosomes that moved faster in a straight-line and were more likely to undergo an acrosome reaction (p ≤ 0.05) compared with their counterparts in the Low fertility group. Ejaculates from High fertility boars contained the greatest concentrations of three seminal plasma proteins (25.9 kD/5.9 pI; 55.1 kD/4.8 pI; and 70.1 kD/5.2 pI; p ≤ 0.05), whereas concentrations of a 19.1 kD/6.8 pI were highest in semen from Low fertility boars (p ≤ 0.05). Multiple regression analyses indicated that concentrations of the 25.9 kD/5.9 pI seminal plasma protein explained 66% of the variation observed in the proportion of pigs sired within a litter among boars (p ≤ 0.00001). These results demonstrate that heterospermic inseminations and subsequent paternity testing is an effective technique for defining relationships between common semen quality tests and fertility, especially in situations where reproductive performance of all the boars is high. Motility, normal acrosome morphology, average linear velocity of motile sperm, and the proportion of sperm capable of an acrosome reaction were all positively associated with boar fertility. However, concentrations of a 25.9 kD/5.9 pI seminal plasma protein were the best single semen characteristic for ranking boars in terms of their fertility.}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Flowers, W. L. and Deller, F. and Stewart, K. R.}, year={2016}, month={Nov}, pages={123–131} }
 @article{huang_ashwell_fry_lloyd_flowers_spears_2015, title={Effect of dietary copper amount and source on copper metabolism and oxidative stress of weanling pigs in short-term feeding}, volume={93}, ISSN={["1525-3163"]}, DOI={10.2527/jas.2014-8082}, abstractNote={Forty-eight weanling barrows were used to determine the effects of amount and source of dietary Cu on Cu metabolism, oxidative stress in the duodenum, and VFA ratios in the cecum of weanling pigs in short-term feeding. At 21 d of age, newly weaned pigs were stratified by BW (7.03 ± 1.20 kg) and equally assigned to 1 of the following dietary treatments: 1) control (5 mg supplemental Cu/kg diet from CuSO4), 2) 225 mg supplemental Cu/kg diet from CuSO4, or 3) 225 mg supplemental Cu/kg diet from tribasic Cu chloride (TBCC). Pigs were housed 2 pigs per pen and were fed a complex diet until harvest on d 11 and 12. During harvest, bile and liver were obtained for mineral analysis, and liver samples were obtained for analysis of mRNA expression of Cu regulatory proteins. Digesta of duodenum, proximal jejunum, and ileum were collected for soluble Cu analysis. Mucosal scrapings of duodenum, proximal jejunum, and ileum were obtained for analysis of mucosal Cu concentration and mRNA expression of Cu regulatory proteins. Duodenal mucosal scrapings were also collected for analysis of malondialdehyde (MDA). Pigs fed high Cu had markedly greater (P < 0.0001) Cu concentrations in the duodenal, proximal jejunal, and ileal mucosa than controls. Copper in the duodenal mucosa was greater (P = 0.003) in CuSO4 than TBCC pigs. Duodenal MDA concentrations were greater (P = 0.003) in CuSO4 vs. control pigs and tended (P = 0.06) to be greater than in TBCC pigs. Duodenal antioxidant 1 (Atox1) mRNA was downregulated (P < 0.01) in pigs fed high Cu compared to controls and was not affected by Cu source. Compared with control pigs, those fed CuSO4 and TBCC had greater (P < 0.001) liver and bile Cu concentrations. Liver Cu was also greater (P = 0.0007) in TBCC than CuSO4-fed pigs. Hepatic Cu transporting β-polypeptide ATPase (Atp7b) was upregulated (P = 0.02) in the Cu-supplemented pigs compared with controls and did not differ among Cu sources. The acetate:propionate ratio in cecal contents was much greater in pigs supplemented with 225 mg Cu/kg diet than in controls. When fed at 225 mg Cu/kg diet, TBCC may cause less oxidative stress in the duodenum than CuSO4. Feeding weanling pigs increased Cu resulted in modulation of duodenal and liver at the transcription level.}, number={6}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Huang, Y. L. and Ashwell, M. S. and Fry, R. S. and Lloyd, K. E. and Flowers, W. L. and Spears, J. W.}, year={2015}, month={Jun}, pages={2948–2955} }
 @misc{flowers_2015, title={Factors Affecting the Efficient Production of Boar Sperm}, volume={50}, ISSN={["1439-0531"]}, DOI={10.1111/rda.12529}, abstractNote={Contents}, journal={REPRODUCTION IN DOMESTIC ANIMALS}, author={Flowers, W. L.}, year={2015}, month={Jul}, pages={25–30} }
 @article{maile_busby_gollahon_flowers_garbacik_garbacik_stewart_nichols_bellinger_patel_et al._2014, title={Blocking Ligand Occupancy of the alpha V beta 3 Integrin Inhibits the Development of Nephropathy in Diabetic Pigs}, volume={155}, ISSN={["1945-7170"]}, DOI={10.1210/en.2014-1318}, abstractNote={Hyperglycemia stimulates secretion of αVβ3 ligands from vascular cells, including endothelial cells, resulting in activation of the αVβ3 integrin. This study determined whether blocking ligand occupancy of αVβ3 would inhibit the development of diabetic nephropathy. Ten diabetic pigs received an F(ab)2 fragment of an antibody directed against the extracellular domain of the β3-subunit, and 10 received a control IgG F(ab)2 for 18 weeks. Nondiabetic pigs excreted 115 ± 50 μg of protein/mg creatinine compared with control F(ab)2-treated diabetic animals (218 ± 57 μg/mg), whereas diabetic animals treated with the anti-β3 F(ab)2 excreted 119 ± 55 μg/mg (P < .05). Mesangial volume/glomerular volume increased to 21 ± 2.4% in control-treated diabetic animals compared with 14 ± 2.8% (P < .01) in animals treated with active antibody. Diabetic animals treated with control F(ab)2 had significantly less glomerular podocin staining compared with nondiabetic animals, and this decrease was attenuated by treatment with anti-β3 F(ab)2. Glomerular basement membrane thickness was increased in the control, F(ab)2-treated diabetic animals (212 ± 14 nm) compared with nondiabetic animals (170 ± 8.8 nm), but it was unchanged (159.9 ± 16.4 nm) in animals receiving anti-β3 F(ab)2. Podocyte foot process width was greater in control, F(ab)2-treated, animals (502 ± 34 nm) compared with animals treated with the anti-β3 F(ab)2 (357 ± 47 nm, P < .05). Renal β3 tyrosine phosphorylation decreased from 13 934 ± 6437 to 6730 ± 1524 (P < .01) scanning units in the anti-β3-treated group. We conclude that administration of an antibody that inhibits activation of the β3-subunit of αVβ3 that is induced by hyperglycemia attenuates proteinuria and early histologic changes of diabetic nephropathy, suggesting that it may have utility in preventing the progression of this disease complication.}, number={12}, journal={ENDOCRINOLOGY}, author={Maile, Laura A. and Busby, Walker H. and Gollahon, Katherine A. and Flowers, William and Garbacik, Nikol and Garbacik, Stefani and Stewart, Kara and Nichols, Timothy and Bellinger, Dwight and Patel, Amit and et al.}, year={2014}, month={Dec}, pages={4665–4675} }
 @article{bohrer_flowers_kyle_johnson_king_spruill_thompson_schroeder_boler_2014, title={Effect of gonadotropin releasing factor suppression with an immunological on growth performance, estrus activity, carcass characteristics, and meat quality of market gilts}, volume={92}, ISSN={["1525-3163"]}, DOI={10.2527/jas.2014-7756}, abstractNote={Objectives were to evaluate the administration of an anti-gonadotropin releasing factor (GnRF) analog on suppression of estrus, consistency of feed intake, and growth performance in market gilts and to investigate the impact the physiological changes would have on carcass characteristics and fresh meat quality. Gonadotropin releasing factor stimulates the anterior pituitary to release luteinizing hormone that acts on the ovary to induce follicle development and indirectly initiates ovulation. Improvest (Zoetis, Kalamazoo, MI) contains an incomplete version of naturally occurring GnRF and causes the production of anti-GnRF antibodies that bind to the GnRF receptor and thus render GnRF inactive. This in turn suppresses estrus in female pigs. Gilts were initially separated into 10 blocks based on age and then within each block allotted to a pen (n = 114; 5 pigs/pen) based on BW. Gilts received the first dose at 12 wk of age and the second dose at 16 wk of age, were exposed to a boar daily from 20 to 26 wk of age, and were slaughtered at 26 wk of age (10 wk after second dose). Meat quality was analyzed on the 2 gilts closest to pen average ending live weight in 5 of the 10 blocks. Pen served as the experimental unit for all data analysis. During the 15-wk finishing period, ADG was 0.03 kg greater (P < 0.01) and G:F was 0.009 greater (P = 0.02) in gilts administered GnRF suppression (treated) compared with untreated gilts (control). The majority of improvements in growth performance were observed from 16 to 20 wk of age (4 wk after second dose), as ADG was 0.07 kg greater (P < 0.001) and G:F was 0.021 greater (P < 0.01) in treated gilts compared with control gilts. Ovarian weights were reduced (P < 0.0001) by 64.15% and gilts exhibiting puberty were reduced by 87.80% (P < 0.001) in treated gilts compared with control gilts. Back fat depth was 3.78 mm greater (P < 0.0001) and estimated lean was 1.31 percentage units less (P < 0.0001) in treated gilts compared with control gilts. With the exception of subjective color, there were no differences (P ≥ 0.12) in meat quality parameters between treated and control gilts. Subjective color was darker (P = 0.03) in treated gilts compared with control gilts. These data suggest market gilts treated with an anti-GnRF analog had suppressed estrus and episodical changes in ADFI, while they had improved feed efficiency, increased ADG, and increased back fat depth when compared with gilts without an anti-GnRF analog treatment.}, number={10}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Bohrer, B. M. and Flowers, W. L. and Kyle, J. M. and Johnson, S. S. and King, V. L. and Spruill, J. L. and Thompson, D. P. and Schroeder, A. L. and Boler, D. D.}, year={2014}, month={Oct}, pages={4719–4724} }
 @article{lovercamp_stewart_lin_flowers_2013, title={Effect of dietary selenium on boar sperm quality}, volume={138}, ISSN={0378-4320}, url={http://dx.doi.org/10.1016/j.anireprosci.2013.02.016}, DOI={10.1016/j.anireprosci.2013.02.016}, abstractNote={The primary objective of this research was to evaluate the effect of long-term dietary selenium supplementation of commercial swine diets on semen production and sperm quality. The dietary treatments were a non-supplemented basal diet or the basal diet supplemented with 0.3 ppm selenium in either an organic or inorganic form. A secondary objective was to determine if there were any beneficial effects of dietary selenium supplementation on changes in sperm quality during storage of semen post collection. Boars were fed dietary treatments from weaning at 20.97 ± 0.18 d of age until the study was terminated when they were 382.97 ± 0.18 d of age. Boars (n = 6 per treatment) were maintained on a 1 time per week collection frequency for 5 months. Immediately after this, boars were collected six times over a 4 day period. Ejaculates were extended in a commercially available, 5-day semen extender and evaluated on day 1 and 6 of storage post-collection. Boars fed the organic selenium had higher (P < 0.01) plasma levels of selenium compared to control boars and similar levels to those supplemented with the inorganic form (P = 0.18). Dietary treatment did not affect (P > 0.2) volume, concentration, total sperm in the ejaculate, sperm motility, progressive motility, morphology, lipid peroxidation, or glutathione peroxidase activity. These results indicate that supplementing a basal diet with organic or inorganic selenium did not affect semen quantity or sperm quality in fresh ejaculates nor did it appear to have any beneficial latent effects in extended semen stored post collection.}, number={3-4}, journal={Animal Reproduction Science}, publisher={Elsevier BV}, author={Lovercamp, K.W. and Stewart, K.R. and Lin, X. and Flowers, W.L.}, year={2013}, month={May}, pages={268–275} }
 @article{zhao_flowers_saraiva_yeum_kim_2013, title={Effect of social ranks and gestation housing systems on oxidative stress status, reproductive performance, and immune status of sows1}, volume={91}, ISSN={0021-8812 1525-3163}, url={http://dx.doi.org/10.2527/jas.2013-6388}, DOI={10.2527/jas.2013-6388}, abstractNote={Ninety-six multiparous sows were randomly assigned into 2 different gestation housing systems on d 35 of gestation: individual gestational crates (n = 24) or small groups with 3 sows in gestational pens (n = 24). Sows were classified into 4 treatments based on gestation housing systems and social ranks within each gestational pen: sows housed in individual gestational crates were in control treatment (CON), and sows destined to high, middle, or low social ranks within each pen were classified into high social rank treatment (HR), middle social rank treatment (MR), and low social rank treatment (LR). The social rank of sows within a pen was determined by their winning percentage during aggressive interactions observed for a 4-d period after mixing on d 35 of gestation. Plasma samples collected from each sow on d 35, 60, 90, and 109 of gestation and d 1 and 18 of lactation were used to determine concentrations of malondialdehyde (MDA), protein carbonyls, 8-hydroxy-deoxyguanosine (8-OHdG), IgG, and IgM. Sows in HR had higher (P < 0.05) body weight during gestation and lactation, smallest (P < 0.05) litter weight at birth, increased (P < 0.05) number of stillborn than sows in MR and LR, and tended to have decreased (P = 0.073, P = 0.064) number of born alive compared with sows in CON and LR. Sows in LR had lower farrowing rate compared with sows in MR. Plasma concentration of protein carbonyl in HR was higher (P < 0.05) than that in MR on d 3 of lactation. Plasma concentrations of 8-OHdG in LR was greater (P < 0.05) than that in HR on d 90 of gestation, d 3 and 18 of lactation, and greater (P < 0.05) than CON on d 18 of lactation. The reproductive performance of sows from all of the social ranks was related to their oxidative stress status during gestation and lactation. Collectively, the reproductive performance, oxidative stress status, and immune status did not differ between sows housed in gestational crates (CON) and pens (HR + MR + LR). Sows in CON and MR did not show inferior reproductive performance during gestation and lactation. Sows in HR and LR had increased oxidative damage during late gestation and lactation which could contribute to the reduced litter size and litter weight in HR and lower farrowing rate in LR.}, number={12}, journal={Journal of Animal Science}, publisher={Oxford University Press (OUP)}, author={Zhao, Y. and Flowers, W. L. and Saraiva, A. and Yeum, K.-J. and Kim, S. W.}, year={2013}, month={Dec}, pages={5848–5858} }
 @article{flowers_2013, title={TRIENNIAL REPRODUCTION SYMPOSIUM: Sperm characteristics that limit success of fertilization}, volume={91}, ISSN={["1525-3163"]}, DOI={10.2527/jas.2012-5945}, abstractNote={Current industry estimates of reproductive performance for cattle, sheep, and swine operations indicate that males contribute significantly to fertility failures. This appears to be due to the use of subfertile individuals and emphasizes the need for additional research in identifying characteristics of sperm that compromise fertilization. In theory, sperm characteristics, such as motility or the percentage of normal sperm, form a positive relationship with fertility that reaches a certain maximal fertility (i.e., an asymptotic relationship). It is clear that variation exists among males in terms of how fertility responds to increasing sperm dosage or numbers of normal sperm, both in the slope of the curve and the point at which the fertility reaches a maximum. Variations along the linear portion of fertility curves are due to compensable traits that are involved with the ability of sperm to penetrate the zona pellucida. It appears that most fertility curves reach their plateau when 70% of sperm possess a given compensable trait. The level of fertility at which the plateau occurs is determined by noncompensable traits that are associated with binding of sperm to the oolemma, syngamy, and subsequent development of the zygote. Several studies have shown differences in fertility among males that have similar levels of compensable traits but differed in their noncompensable characteristics. Compensable and noncompensable traits can estimate either individual or functional characteristics of sperm. Intuitively, functional traits such as in vitro penetration should provide a better indication of fertilization than individual ones such as motility. However, correlations of both types with fertility are very similar. Reasons for this may be related to how characteristics of sperm cells are influenced by the female reproductive tract after insemination. Sperm capacitation is a functional trait in boars that is quite different in vitro versus in vivo. If this relationship holds true for other traits, then development of tests that account for this variation are critical for further elucidation of sperm characteristics that limit fertility.}, number={7}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Flowers, W. L.}, year={2013}, month={Jul}, pages={3022–3029} }
 @article{fry_ashwell_lloyd_o'nan_flowers_stewart_spears_2012, title={Amount and source of dietary copper affects small intestine morphology, duodenal lipid peroxidation, hepatic oxidative stress, and mRNA expression of hepatic copper regulatory proteins in weanling pigs}, volume={90}, ISSN={["1525-3163"]}, DOI={10.2527/jas.2011-4403}, abstractNote={Thirty weanling, crossbred barrows (SUS SCROFA) were used to determine the effects of amount and source of dietary Cu on small intestinal morphology and lipid peroxidation, Cu metabolism, and mRNA expression of proteins involved in hepatic Cu homeostasis. At 21 d of age, pigs were stratified by BW (6.33 ± 0.23 kg) and allocated to 1 of the following dietary treatments: i) control (no supplemental Cu; 6.7 mg Cu/kg), ii) 225 mg supplemental Cu/kg diet from Cu sulfate (CuSO(4)), or iii) 225 mg supplemental Cu/kg diet from tribasic Cu chloride (TBCC). Pigs were housed 2 pigs per pen and were fed a 3-phase diet regimen until d 35 or 36 of the study. During harvest, bile and liver were obtained for mineral analysis, and liver samples were also obtained for analysis of liver glutathione (GSH) and mRNA expression of Cu regulatory proteins. Segments of duodenum, proximal jejunum, and ileum were obtained for mucosal morphology, and duodenal mucosal scrapings were collected from all pigs for analysis of malondialdehyde (MDA). Duodenal villus height was reduced in CuSO(4) pigs compared with control (P = 0.001) and TBCC (P = 0.03) pigs. Villus height in the proximal jejunum of CuSO(4) pigs was reduced (P = 0.03) compared with control pigs, but ileal villus height was not affected (P = 0.82) by treatment. Duodenal MDA concentrations were greater (P = 0.03) in CuSO(4) pigs and tended to be greater (P = 0.10) in pigs supplemented with TBCC compared with control pigs. Liver Cu was greater (P = 0.01) in CuSO(4) vs. control pigs, and tended (P = 0.07) to be greater in TBCC pigs than control pigs. Bile Cu concentrations were greater (P < 0.001) in CuSO(4) and TBCC pigs vs. controls and were also greater (P = 0.04) in TBCC vs. CuSO(4) pigs. Total liver GSH concentrations were less (P = 0.02) in pigs fed diets supplemented with CuSO(4) vs. pigs fed control diets but total liver GSH did not differ (P = 0.11) between control and TBCC pigs. Hepatic mRNA of cytochrome c oxidase assembly protein 17 was less (P = 0.01) in CuSO(4) and tended to be less (P = 0.08) in TBCC pigs vs. control pigs. Expression of antioxidant 1 mRNA was greater (P = 0.04) in TBCC pigs and tended to be greater (P = 0.06) in CuSO(4) pigs compared with control pigs. Results of this study indicated that, when fed at 225 mg Cu/kg diet, TBCC may cause less oxidative stress in the duodenum than CuSO(4). Feeding weanling pigs increased Cu resulted in modulation of certain Cu transporters and chaperones at the transcription level.}, number={9}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Fry, R. S. and Ashwell, M. S. and Lloyd, K. E. and O'Nan, A. T. and Flowers, W. L. and Stewart, K. R. and Spears, J. W.}, year={2012}, month={Sep}, pages={3112–3119} }
 @article{kick_tompkins_flowers_whisnant_almond_2012, title={Effects of stress associated with weaning on the adaptive immune system in pigs}, volume={90}, ISSN={["0021-8812"]}, DOI={10.2527/jas.2010-3470}, abstractNote={This study was designed to investigate the effects of weaning age on specific components of the adaptive immune system in pigs. Twenty-three crossbred pigs were randomly assigned to 1 of 3 treatments: weaning at 14 (14D, n = 8), 21 (21D, n = 7), or 28 (28D, n = 8) d of age. Peripheral blood samples, obtained when pigs were 13, 15, 20, 22, 27, 29, and 35 d of age, were analyzed for peripheral blood cell percentages and concentrations of neutrophils, lymphocytes, T cell subsets, mature B cells, and plasma cortisol concentrations. For each of the 3 groups, weaning increased plasma cortisol concentrations (P < 0.001) and reduced BW percentage change (P < 0.017). Lymphocyte concentrations displayed a treatment effect for the 14D (P = 0.074) and 28D (P = 0.014) groups. Albeit inconsistent, lymphocyte concentrations were less in weaned pigs on the day after weaning than in pigs remaining on the sow or weaned at a younger age. Specifically, mature B cells (CD21(+)) and CD4(+)CD8(+) cells decreased (P < 0.05) after weaning at 28 d of age. Other differences occurred among treatments; however, the differences apparently were not associated with weaning. Based upon the immunological measures used in the present study, there was not an explicit benefit to the adaptive immune system for any weaning age. Early weaning did not negatively affect the adaptive immunological competence of pigs as determined by changes in populations of immune cells.}, number={2}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Kick, A. R. and Tompkins, M. B. and Flowers, W. L. and Whisnant, C. S. and Almond, G. W.}, year={2012}, month={Feb}, pages={649–656} }
 @article{yoder_maltecca_cassady_flowers_price_see_2011, title={Breed differences in pig temperament scores during a performance test and their phenotypic relationship with performance}, volume={136}, ISSN={["1878-0490"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79951959362&partnerID=MN8TOARS}, DOI={10.1016/j.livsci.2010.08.004}, abstractNote={Nucleus populations of Chester White, Duroc, Landrace, and Yorkshire boars and gilts (n = 4774) were used to estimate breed differences in temperament and the relationship with performance. Adjusted backfat, adjusted loin depth, days to 113.4 kilograms (DAYS), estimated percent fat-free lean (LEAN), and three temperament scores: load score, scale score, and vocal score were recorded, on a scale of 1 (calm) to 5 (highly excited), during a performance test. Logistic regression for temperament scores included fixed effects of breed, sex, contemporary group (barn-farm-test date), and body weight as a covariate was used. Order that a pig was loaded into the scale, within pen, was included as a fixed effect for load score. After initial analysis, it was determined that vocal score was best described as two categories, vocal or non-vocal, and was reanalyzed accordingly. Linear mixed models for backfat, loin depth, DAYS, and LEAN included fixed effects of breed, sex, and load score, scale score, or vocal score. Growth rate was adjusted to 113.4 kg, while backfat and loin depth were adjusted to 113.4 kg through regression on mean body weight of the respective breed. The odds of increased load score were greater for Landrace (1.62, 1.30; P < 0.01) than Duroc and Yorkshire respectively. Landrace had a greater (P < 0.01) probability of a higher scale and vocal scores compared to Chester White (1.77, 2.37), Duroc (3.31, 3.94) and Yorkshire (2.51, 2.46). Yorkshire had greater (P < 0.01) odds of increased load score (1.25), SS (1.32), and vocal score (1.60) than Duroc. Chester White had greater odds of increased load score and scale score than Duroc (1.58, 1.87) and Yorkshire (1.26, 1.42), respectively. Chester White were 1.66 (P < 0.01) times more likely to have a higher vocal scores than Duroc. Phenotypic correlations (P < 0.01) for scale score with load score, vocal score, backfat, loin depth, DAYS, and LEAN were 0.13, 0.32, − 0.15, − 0.07, 0.10 and 0.17, respectively. Landrace were more excited and vocal in the scale than Chester White, Durocs and Yorkshire. Landrace were more difficult to load into the scale than Durocs and Yorkshire. Chester White were more active in the scale than Durocs and Yorshire, and more vocal than Durocs. Yorkshire were harder to load, more active and vocal than Durocs. It was concluded that temperament differs between breeds, and pigs with lower temperament scores were fatter, had greater loin depth and grew faster.}, number={2-3}, journal={LIVESTOCK SCIENCE}, author={Yoder, C. L. and Maltecca, C. and Cassady, J. P. and Flowers, W. L. and Price, S. and See, M. T.}, year={2011}, month={Apr}, pages={93–101} }
 @article{wrench_pinto_klinefelter_dix_flowers_farin_2010, title={Effect of season on fresh and cryopreserved stallion semen}, volume={119}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2010.02.007}, abstractNote={The objective of this study was to determine the effect of season on sperm quality variables, expression of the fertility-related protein SP22 and selected mRNA transcripts in fresh and cryopreserved stallion sperm. Four stallions were collected in each of the four seasons: summer, fall, winter and spring. Ejaculates were divided and then evaluated for motility, morphology, SP22 staining and expression of selected mRNAs as either fresh semen samples or cryopreserved samples. A significant interaction between season and cryopreservation status was found for total and progressive sperm motility. RNA yield from sperm was not affected by any variable examined. There was no effect of season or cryopreservation on the relative amounts of mRNA for PGK2, TPX1, TIMP3 or ACTB. There was a tendency (P=0.1) for an effect of stallion on the relative amount of ACTB mRNA. The proportion of sperm immunostained for SP22 over the equatorial segment was affected (P<0.05) by stallion. In addition, there was an interaction (P<0.05) between season and cryopreservation status on the percentage of sperm staining for SP22 on the equatorial segment. The correlation among total motility, progressive motility and SP22 immunostaining was much greater (P<0.05) during the breeding season (March and June) than during the non-breeding season (September and December). Based on data analyzed, semen collected in the Northern Hemisphere between March and June may be best suited for cryopreservation.}, number={3-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Wrench, N. and Pinto, C. R. F. and Klinefelter, G. R. and Dix, D. J. and Flowers, W. L. and Farin, C. E.}, year={2010}, month={Jun}, pages={219–227} }
 @article{stewart_flowers_rampacek_greger_swanson_hafs_2010, title={Endocrine, ovulatory and reproductive characteristics of sows treated with an intravaginal GnRH agonist}, volume={120}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2010.04.003}, abstractNote={The present study examined the effectiveness of intravaginal administration of a GnRH agonist, triptorelin, on the induction of the preovulatory LH surge; synchronization of time of ovulation; and reproductive characteristics in weaned sows. Sows were given 100 μg of triptorelin in 0.9, 1.2, or 1.5% methylcellulose gel intravaginally 96 h after weaning and then bred at 8 and 32 h post-treatment. Untreated sows inseminated once each day of estrus served as the positive controls, while females treated with only the methyl cellulose gel and also bred once each day of estrus were negative controls. Sows treated intravaginally with triptorelin exhibited preovulatory LH surges with magnitudes comparable to those that occurred spontaneously in the negative controls. Preovulatory LH surges were initiated over a narrow and well-defined time interval that occurred 4–12 h after treatment in sows receiving triptorelin in 1.2 or 1.5% methyl cellulose gel. As a result, the majority of the sows in these two treatments had ovulations within a 12 h time frame 36–48 h after treatment. In contrast, both the LH surge and ovulation occurred over extended periods of time after weaning in negative controls and sows given triptorelin in 0.9% methylcellulose gel. Farrowing rates and litter size were similar between untreated controls and triptorelin-treated sows that were bred with two fixed timed inseminations. Insemination of sows induced to have ovulations and bred at least once while not in estrus did not have any overt negative effects on reproductive characteristics. These results demonstrate that 100 μg of triptorelin administered intravaginally in a least 1.2% methyl cellulose gel induced a normal preovulatory LH surge and synchronized time of ovulation in weaned sows. Furthermore, there were no obvious changes in reproductive performance when these sows were bred with two fixed time inseminations regardless of whether they exhibited a standing reflex.}, number={1-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Stewart, K. R. and Flowers, W. L. and Rampacek, G. B. and Greger, D. L. and Swanson, M. E. and Hafs, H. D.}, year={2010}, month={Jul}, pages={112–119} }
 @article{wrench_pinto_klinefelter_dix_flowers_farin_2008, title={Effect of season on sperm membrane protein 22 and selected mRNAs in fresh and cryopreserved stallion sperm}, volume={107}, ISSN={0378-4320}, url={http://dx.doi.org/10.1016/j.anireprosci.2008.05.134}, DOI={10.1016/j.anireprosci.2008.05.134}, abstractNote={The objective was to investigate expression patterns of proteins in pyriform sperm, a common morphological abnormality in bull sperm. Ejaculates were collected from sexually mature Holstein bulls (n = 3) twice weekly for 10 weeks (pre-thermal insult samples). Testicular temperature was elevated in all bulls by scrotal insulation for 72 consecutive hours during week 2. Total sperm proteins were extracted from pre- and post-thermal insult sperm samples and subjected to two-dimensional gel electrophoresis. Among the protein spots detected, 131 spots were significantly expressed (False Detection Rate < 0.01) with ≥ 2 fold changes between normal and pyriform sperm. Among them, 25 spots with ≥ 4 fold difference in expression patterns were identified using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Expression of several proteins involved in sperm capacitation, sperm–egg interaction and sperm cytoskeletal structure was decreased in pyriform sperm, whereas proteins regulating antioxidant activity, apoptosis and metabolic activity were increased. Contents of reactive oxygen species and ubiquitinated proteins were higher in pyriform sperm. In addition to understanding the molecular basis of functional deficiencies in sperm with specific morphological abnormalities, comparing normal versus morphologically abnormal sperm appeared to be a suitable experimental model for identifying important sperm functional proteins.To our knowledge, this study is the first report on differential expression of proteins in pyriform bovine sperm versus morphologically normal sperm. We report that expression of several proteins involved in sperm capacitation, sperm–egg interaction and sperm cytoskeletal structure was decreased in pyriform sperm, whereas proteins which regulate antioxidant activity, apoptosis and metabolic activity were increased. Contents of reactive oxygen species and ubiquitinated proteins were higher in pyriform sperm. In addition to understanding the molecular basis of functional deficiencies in sperm with specific morphological abnormalities, our results suggest that comparing normal versus morphologically abnormal sperm appeared to be a suitable experimental model for identifying important sperm functional proteins.}, number={3-4}, journal={Animal Reproduction Science}, publisher={Elsevier BV}, author={Wrench, N. and Pinto, C.R.F. and Klinefelter, G.R. and Dix, D.J. and Flowers, W.L. and Farin, C.E.}, year={2008}, month={Sep}, pages={357} }
 @article{flowers_2008, title={Genetic and phenotypic variation in reproductive traits of AI boars}, volume={70}, ISSN={["1879-3231"]}, DOI={10.1016/j.theriogenology.2008.06.016}, abstractNote={The primary objective of this paper is to review our current understanding of phenotypic variation in reproductive traits of AI boars. The proportion of boars that cannot be trained for collection in commercial studs is low and differences among genetic lines are small. In contrast, there is a considerable variation in sperm production and significant differences are present among genotypes. The general pattern is for sperm numbers to increase rapidly between 9 and 13 months of age and then gradually reach a plateau. This initial period of enhanced production occurs over a longer period in some genetic lines, resulting in differences of 30 × 109 sperm cells or more per ejaculate. There also are genetic lines of boars that seem to have a high “heat tolerance”. Decreases in sperm production during periods of high environmental temperatures average 5–7% in these lines, compared with 15–20% in others. Finally, there are boars currently being used in the industry that are capable of producing exceptional fertility results with low numbers of sperm. Unfortunately, several breeding practices common to swine AI make their routine identification difficult. Based on the phenotypic variation observed in modern terminal sire lines of AI boars, current prospects for influencing sperm production, boar fertility, and mounting behaviours through genetic selection are viewed as being good, moderate to low, and poor, respectively.}, number={8}, journal={THERIOGENOLOGY}, author={Flowers, William L.}, year={2008}, month={Nov}, pages={1297–1303} }
 @article{collins_flowers_shanks_miller_2008, title={Porcine sperm zona binding ability as an indicator of fertility}, volume={104}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2007.01.012}, abstractNote={The escalated use of artificial insemination in swine has increased the importance of determining fertility of a semen sample before it is used. Multiple laboratory assays have been developed to assess fertilizing potential but they have yielded inconsistent results. This experiment sought to determine the relationship between in vitro competitive zona binding ability and in vivo fertility based on heterospermic inseminations and paternity testing. The zona pellucida binding ability and fertility of sperm from 15 boars was assessed by comparing sperm from one boar with sperm from other individual boars in a pairwise fashion using four ejaculates. The relationship of zona binding ability to the mean number of piglets sired per litter for each boar as well as historic fertility data (litter size and farrowing rate) was assessed. The in vitro competition assay consisted of labeling sperm from each boar of the pair with a different fluorophore and incubating an equal number of sperm from each boar in the same droplet with porcine oocytes. The competitive assay was highly effective in ranking boars by zona binding ability (R2 = 0.94). Paternity testing using microsatellite markers was used to determine the mean number of piglets sired per litter for each boar during heterospermic inseminations. The pairwise heterospermic insemination assay was effective in ranking boar fertility (R2 = 0.59). Using historical data from these boars, average litter size and farrowing rate were correlated (r = 0.81, p < 0.001). However, zona binding ability was not significantly correlated with historic farrowing rate data or historic average litter size. Boar sperm zona binding ability was also not correlated significantly with the mean number of piglets sired per litter following heterospermic insemination. But the number of piglets sired by each boar was related to a combination of zona binding ability, sperm motility, normal morphology, acrosomal integrity, and the presence of distal droplets (R2 = 0.70). These results suggest that zona binding ability is not an accurate predictor of fertilizing ability when used alone; however, when coupled with other sperm assessments, fertility may be predicted successfully.}, number={1}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Collins, E. D. and Flowers, W. L. and Shanks, R. D. and Miller, D. J.}, year={2008}, month={Feb}, pages={69–82} }
 @article{belstra_flowers_croom_degroot_see_2005, title={Urinary excretion of collagen degradation markers by sows during postpartum uterine involution}, volume={85}, ISSN={["1873-2232"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-8844250111&partnerID=MN8TOARS}, DOI={10.1016/j.anireprosci.2004.04.035}, abstractNote={Incomplete uterine involution is the putative cause of the increased embryo mortality and reproductive failure often exhibited by sows that lactate for less than 21 days. Since such short lactation lengths are common in American swine production, an effective technique to monitor the postpartum involution process and test this hypothesis might be valuable. Rapid and extensive catabolism of uterine collagen is essential for normal postpartum involution. The objective of this study was to characterize postpartum excretion of two biochemical markers of collagen degradation. In experiment I, urine samples were collected from five sows every other day from the day before parturition (day −1), through a 21-day lactation, to day 8 postweaning. The collagen crosslinks hydroxylysyl pyridinoline (HP), which is present in many tissues, and lysyl pyridinoline (LP), which is primarily concentrated in bone, were assayed by both ELISA and HPLC. Urinary levels of both free (ELISA) and total (HPLC) HP and LP increased (P < 0.001) approximately two-fold during lactation. The mean molar ratio of total HP:LP increased (P < 0.001) from 6.6 ± 1.6 at day 1 to a maximum of 10.2 ± 1.5 at day 7 postpartum and averaged 9.1 ± 0.3 for the entire sampling period. These data are consistent with a postpartum increase of soft tissue collagen catabolism since bone has a low HP:LP ratio of 4 and soft tissues like the uterus have a high HP:LP ratio of ≥20 because they contain only trace amounts of LP. Since HPLC (total) and ELISA (free) crosslinks estimates were highly correlated (r = 0.85–0.91, P < 0.001) in experiment I, only the less technical ELISA technique was used in experiment II. Urine samples were collected from 21 sows every third day from day 1 to 19 of lactation. Sows from this second group exhibited one of four distinct crosslinks excretion patterns: peak on day 1 (n = 3), peak on day 7 (n = 4), peak on day 10, 13 or 16 (n = 7), or no peak (n = 7). This variation of postpartum crosslinks excretion among sows was not related to parity, body weight, lactation body weight change, litter size, or litter birth weight. Overall, data from experiments I and II indicate that urinary HP does increase postpartum in a pattern temporally consistent with uterine involution. However, significant variation among sows in the magnitude and timing of peak HP excretion was evident.}, number={1-2}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Belstra, BA and Flowers, WL and Croom, WJ and DeGroot, J and See, MT}, year={2005}, month={Jan}, pages={131–145} }
 @article{creech_spears_flowers_hill_lloyd_armstrong_engle_2004, title={Effect of dietary trace mineral concentration and source (inorganic vs. chelated) on performance, mineral status, and fecal mineral excretion in pigs from weaning through finishing}, volume={82}, DOI={10.2527/2004.8272140x}, abstractNote={Two hundred and sixteen weanling gilts (6.65+/-0.08 kg) were used to determine the effects of decreasing supplemental concentrations of Zn, Cu, Fe, and Mn, and trace mineral source (inorganic vs. chelated) on growth performance, mineral status, and fecal mineral concentrations from weaning through development. The study was conducted over three trials with 72 pigs in each trial. Gilts were blocked by weight and randomly assigned to either 1) control, 2) reduced inorganic, or 3) reduced chelated trace minerals. The control diet was supplemented with 25, 150, 180, and 60 mg/kg of Cu, Zn, Fe, and Mn (in sulfate forms), respectively, during the nursery phase and 15, 100, 100, and 40 mg/kg of supplemental Cu, Zn, Fe, and Mn, respectively, during the growing and gilt-developer phases. Reduced inorganic and reduced chelated treatments were supplemented during all phases with 5, 25, 25, and 10 mg/kg of Cu, Zn, Fe, and Mn, respectively. The reduced chelated treatment supplied 50% of the supplemental Cu, Zn, Fe, and Mn in the form of metal proteinates, with the remainder from sulfate forms. Performance by control pigs did not differ from pigs fed the reduced trace mineral treatments during the nursery and grower-development periods. Gain:feed was lower (P < 0.05) for pigs fed the reduced inorganic compared with those fed the reduced chelated treatment during the nursery period. Trace mineral source did not affect performance during the growing or gilt-developer phase. Plasma Zn concentration and alkaline phosphatase activity were higher (P < 0.01) in control pigs than in those receiving reduced trace minerals during the nursery and growing phases. Plasma Cu concentration and ceruloplasmin activity were generally not affected by treatment. Hemoglobin concentrations were lower (P < 0.05) for the reduced inorganic compared with the reduced chelated treatment in the nursery phase. Fecal concentrations of Cu, Zn, and Mn were lower (P < 0.05) in pigs fed reduced trace minerals than in controls during all production phases. Fecal Zn concentration during the nursery and fecal Cu concentrations during the growing and gilt-developer phases were lower (P < 0.05) in pigs fed the reduced chelated compared with the reduced inorganic treatment. Results indicate that reducing the concentrations of Zn, Cu, Mn, and Fe typically supplemented to pig diets will greatly decrease fecal mineral excretion without negatively affecting pig performance from weaning through development.}, number={7}, journal={Journal of Animal Science}, author={Creech, B. L. and Spears, J. W. and Flowers, W. L. and Hill, G. M. and Lloyd, K. E. and Armstrong, T. A. and Engle, T. E.}, year={2004}, pages={2140–2147} }
 @article{belstra_flowers_see_2004, title={Factors affecting temporal relationships between estrus and ovulation in commercial sow farms}, volume={84}, ISSN={["1873-2232"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-4143080539&partnerID=MN8TOARS}, DOI={10.1016/j.anireprosci.2004.02.005}, abstractNote={The main objective was to examine effects of season, parity, genotype, lactation length, and weaning-to-estrus interval on duration of estrus (DE) and onset of estrus-to-ovulation interval (EOI) in three sow farms. Detection of estrus and ovulation by the back-pressure test and transabdominal ultrasonography, respectively, were performed every 6 h from day 2–10 postweaning in 535 sows (approximately 89 per farm per season). The average weaning-to-estrus interval, DE, and EOI of the 501 sows that returned to estrus by day 10 postweaning were 4.6±0.1 days, 55.2±0.5 h, and 41.8±0.5 h, respectively. Farm × season (P<0.01), parity×season (P<0.05), and farm×weaning-to-estrus interval (P<0.05) interactions for DE and EOI were detected. Sows weaned in the summer had an 8 h longer (P<0.001) DE and EOI than those weaned in the spring on farms 1 and 3. On farm 2 however, DE and EOI did not differ (P=0.09) in sows weaned in summer versus spring. On each farm, parity 3 and ≥4 sows had a 4.5 h longer (P<0.05) DE and EOI than parity 1 and 2 sows in the summer, but there were no differences (P>0.11) in DE or EOI among parity classes in the spring. There was a linear decrease of DE (P<0.001) and EOI (P<0.05) as weaning-to-estrus interval increased from the 3 to the ≥7 day class on each farm. However, the range of weaning-to-estrus interval that exhibited a stepwise decrease of DE and EOI was narrower on farm 1 (3–5 days) than farms 2 and 3 (3–6 days). Only farms 1 and 3 had multiple genotypes. Genotype did not affect (P>0.14) DE on either farm, but the EOI of genotype B was 4 h shorter (P<0.05) than genotype C on farm 1. On each farm, DE decreased linearly (P<0.01) as lactation length increased from ≤13 to ≥20 days. In general, factors that affected EOI also affected (P<0.05) the percentage of inseminations that occurred within 24 h pre- to 3 h post-ovulation. These data indicate that factors other than weaning-to-estrus interval, such as season and parity, can significantly alter DE and EOI. However, the effects of season and weaning-to-estrus interval on DE and EOI can be inconsistent among different farms.}, number={3-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Belstra, BA and Flowers, WL and See, MT}, year={2004}, month={Sep}, pages={377–394} }
 @article{van heugten_o'quinn_funderburke_flowers_spears_2004, title={Growth performance, carcass characteristics, plasma minerals, and fecal mineral excretion in grower-finisher swine fed diets with levels of trace minerals lower than common industry levels}, volume={12}, number={5}, journal={Journal of Swine Health and Production}, author={Van Heugten, E. and O'Quinn, P. R. and Funderburke, D. W. and Flowers, W. L. and Spears, J. W.}, year={2004}, pages={237–241} }
 @article{popwell_flowers_2004, title={Variability in relationships between semen quality and estimates of in vivo and in vitro fertility in boars}, volume={81}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2003.08.007}, abstractNote={The present experiment was designed to characterize relationships between common semen quality and fertility estimates for three boars known to differ in farrowing rate, number of pigs born alive, and monospermic penetration rate. The approach chosen to accomplish this was to monitor semen quality from these boars and use their semen alternately for either artificial insemination or in vitro fertilization for 40 weeks. This strategy relied on the variability in semen quality parameters that normally occurs in an individual boar over time. When comparisons were made among boars, farrowing rates, numbers of pigs born alive, and monospermic penetration rates were significantly different, but progressive motility, normal head and tail morphology, and acrosome morphology were not. However, when comparisons were made among ejaculates within individual boars, there were significant effects of semen quality on both in vivo and in vitro fertility. For boar 3495, the proportion of spermatozoa exhibiting progressive motility and distribution of spermatozoa in a percoll gradient had a positive linear effect on number born alive and monospermic penetration rate, respectively. For boar 2901, quadratic equations best described changes in litter size as a function of progressive motility and normal acrosomes. In addition, monospermic penetration rate increased linearly as normal acrosomes and the proportion of spermatozoa recovered from a percoll gradient increased. For boar 4291, the relationship between progressive motility and number born alive and between normal acrosomes and number of pigs born alive were also quadratic. However, a significant linear relationship was present only between normal acrosomes and monospermic penetration rate. These results demonstrate that simply relying on the means of common semen quality estimates from some boars has limited value in terms of being used as a prospective indicator of their in vivo or in vitro fertility. In contrast, characterization of relationships between semen quality and fertility estimates is useful for estimating differences in the fertility of ejaculates from individual boars. However, both quantitative and qualitative differences in these relationships among boars are present and a given semen quality estimate that is a good predictor of in vivo or in vitro fertilization for one boar, may not be applicable for others.}, number={1-2}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Popwell, JM and Flowers, WL}, year={2004}, month={Mar}, pages={97–113} }
 @article{kegley_spears_flowers_schoenherr_2002, title={Iron methionine as a source of iron for the neonatal pig}, volume={22}, ISSN={["0271-5317"]}, DOI={10.1016/s0271-5317(02)00434-7}, abstractNote={Neonatal pigs (143) were used to determine if adequate iron (Fe) would be stored following a single oral dose of Fe methionine (FeMet) to prevent anemia through 21 d of age. Treatments consisted of: control (no Fe), 200 mg injectable Fe as gleptoferron within 12 h of birth (at birth), 100 or 200 mg Fe as FeMet orally at birth, or 200 mg Fe as FeMet or FeSO4 orally on d 3. Pigs given injectable Fe had higher hemoglobin concentrations than other treatments at 14 and 21 d. Utilization of Fe from FeMet was greatest when given at 3 d compared to at birth. Based on hemoglobin concentrations at 21 d, relative bioavailability of Fe from FeMet given on d 3 was 180% compared to FeSO4. Iron methionine given orally was a safe, effective source of Fe, but a single oral dose of FeMet was not equivalent to injectable Fe.}, number={10}, journal={NUTRITION RESEARCH}, author={Kegley, EB and Spears, JW and Flowers, WL and Schoenherr, WD}, year={2002}, month={Oct}, pages={1209–1217} }
 @article{armstrong_flowers_spears_nielsen_2002, title={Long-term effects of boron supplementation on reproductive characteristics and bone mechanical properties in gilts}, volume={80}, DOI={10.2527/2002.801154x}, abstractNote={An experiment was conducted to determine long-term effects of dietary boron (B) on reproductive and bone characteristics in gilts. Weanling gilts (n = 50) were allotted to 10 pens based on weaning weight and litter origin. Pens were randomly assigned to receive one of two dietary treatments that consisted of a basal diet low in B (control) and the basal diet supplemented with 5 mg of B/kg diet as sodium borate. Gilts remained on their respective experimental diets throughout the nursery phase, growing-finishing phase, sexual maturity, breeding, gestation, and lactation. The day of first observed standing estrus was defined as puberty, and each pubertal gilt was bred via AI at the second observed standing estrus. Eight randomly selected gilts per treatment were slaughtered at d 35 of gestation for the assessment of embryonic and reproductive characteristics, bone characteristics, and tissue B concentrations. The remaining pregnant gilts (control, n = 11; 5 mg supplemental B/kg diet, n = 10) farrowed, and litter characteristics at farrowing and weaning were determined. Age at puberty was not affected (P = 0.72) by B, and neither were the number of corpora lutea on the ovaries (P = 0.44) or the total number of embryos (P = 0.95) at d 35 of gestation. Boron supplementation increased (P = 0.05) pig weaning weight and tended (P = 0.11) to increase pig birth weight; however, no other litter characteristics were affected (P > 0.12) by B. Extrinsic and intrinsic strength measures of bone were increased (P < 0.09) by B. Fat-free bone ash percentage and bone mineral concentrations were not affected (P > or = 0.19) by dietary B. Supplemental B increased (P < or = 0.06) the B concentrations of the muscle, liver, and reproductive tissues. Serum osteocalcin concentrations tended (P = 0.13) to be increased by dietary B, which may be related to increased bone turnover in B-supplemented gilts. Results indicate that B may have beneficial effects upon reproductive and bone characteristics.}, number={1}, journal={Journal of Animal Science}, author={Armstrong, T. A. and Flowers, W. L. and Spears, J. W. and Nielsen, F. H.}, year={2002}, pages={154–161} }
 @article{armstrong_flowers_britt_1999, title={Control of the weaning-to-estrus interval in sows using gonadotropins and prostaglandins during lactation}, volume={77}, DOI={10.2527/1999.7792533x}, abstractNote={Two experiments were conducted to examine the effectiveness of various strategies using gonadotropins to induce ovulation during lactation as a means of controlling the weaning-to-estrus interval in sows. The objective of Exp. 1 was to examine the efficacy of various gonadotropin regimens for induction of ovulation during lactation. Primiparous (n = 60) and multiparous (n = 83) crossbred sows were assigned, before farrowing, to one of four treatments: no injection (control); 1,000 IU hCG on d 0 (hCG-0; d 0 = day of farrowing); P.G. 600 + 1,000 IU hCG 4 and 7 d after farrowing, respectively (hCG-7); or P.G. 600 + 1,000 IU hCG 11 and 14 d after farrowing, respectively (hCG-14). Sows were weaned on 18 +/- 2 d after farrowing and monitored daily for estrus via exposure to mature boars. The criterion for determining the induction of ovulation was a sustained increase in serum progesterone concentrations above 4.0 ng/mL. The most consistent response to exogenous gonadotropins was on d 0, with an 80% response in primiparous sows (12/15) and a 71% response in multiparous sows (15/21). Weaning-to-estrus intervals for multiparous sows were longer (P = .05) for hCG-14 and hCG-7 than for control and hCG-0 sows. Weaning-to-estrus intervals for primiparous sows were longer (P = .05) for the hCG-14 than for the hCG-0 treatment. The objective of Exp. 2 was to ascertain the effects of postpartum treatment with hCG (1,000 IU) on d 0 and PGF2alpha (10 mg) at d 14 on the weaning-to-estrus interval in multiparous sows weaned at d 14 after birth. Before farrowing, sows (n = 60) were randomly assigned to one of four treatments: positive control, weaning at d 21; negative control, weaning at d 14; hCG within 24 h after farrowing, weaning at d 14; or hCG within 24 h after farrowing and PGF2alpha at weaning, weaning at d 14. Weaning-to-estrus intervals were longer (P = .05) in sows receiving PGF2alpha than in the other treatments. Results indicate that it is possible to induce ovulation immediately after farrowing, using a single injection of hCG, and this strategy can be used to uncouple weaning from the resumption of reproductive activity. However, the administration of PGF2alpha at 14 d after farrowing did not consistently cause regression of the induced corpora lutea.}, number={9}, journal={Journal of Animal Science}, author={Armstrong, T. A. and Flowers, W. L. and Britt, Jack}, year={1999}, pages={2533–2539} }
 @article{flowers_1998, title={Improving boar fertility}, volume={9}, number={1998}, journal={Advances in Pork Production}, author={Flowers, B.}, year={1998}, pages={1–11} }
 @article{flowers_1998, title={New ideas on boar and sow fertility examined}, volume={70}, number={35}, journal={Feedstuffs}, author={Flowers, W. L.}, year={1998}, pages={12–131923} }
 @article{petters_alexander_wells_collins_sommer_blanton_rojas_hao_flowers_banin_et al._1997, title={Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa}, volume={15}, ISSN={["1087-0156"]}, DOI={10.1038/nbt1097-965}, abstractNote={Patients with retinitis pigmentosa (RP) typically develop night blindness early in life due to loss of rod photoreceptors. The remaining cone photoreceptors are the mainstay of their vision; however, over years or decades, these cones slowly degenerate, leading to blindness. We created transgenic pigs that express a mutated rhodopsin gene (Pro347Leu). Like RP patients with the same mutation, these pigs have early and severe rod loss; initially their cones are relatively spared, but these surviving cones slowly degenerate. By age 20 months, there is only a single layer of morphologically abnormal cones and the cone electroretinogram is markedly reduced. Given the strong similarities in phenotype to that of RP patients, these transgenic pigs will provide a large animal model for study of the protracted phase of cone degeneration found in RP and for preclinical treatment trials.}, number={10}, journal={NATURE BIOTECHNOLOGY}, author={Petters, RM and Alexander, CA and Wells, KD and Collins, EB and Sommer, JR and Blanton, MR and Rojas, G and Hao, Y and Flowers, WL and Banin, E and et al.}, year={1997}, month={Oct}, pages={965–970} }
 @inproceedings{flowers_1997, title={Management of boars for efficient semen production}, volume={52}, booktitle={Control of pig reproduction V: Proceedings of the Fifth International Conference on Pig Reproduction, held at Congress Centre Rolduc, Kerkrade, The Netherlands, June 1997 (Journal of reproduction and fertility. Supplement; no. 52)}, author={Flowers, W. L.}, editor={G. R. Foxcroft, R. D. Geisert and Doberska, C.Editors}, year={1997}, pages={67–78} }
 @inbook{flowers_1997, title={Management of reproduction}, booktitle={Progress in pig science}, publisher={Thrumpton, Nottingham: Nottingham University Press}, author={Flowers, W. L.}, editor={J. Wiseman, M. A. Varley and Chadwick, J. P.Editors}, year={1997}, pages={383–405} }
 @article{flowers_1992, title={Artificial insemination in swine}, volume={13}, number={2}, journal={Agri-Practice}, author={Flowers, W. L.}, year={1992}, pages={36} }
 @article{flowers_alhusen_1992, title={REPRODUCTIVE-PERFORMANCE AND ESTIMATES OF LABOR REQUIREMENTS ASSOCIATED WITH COMBINATIONS OF ARTIFICIAL-INSEMINATION AND NATURAL SERVICE IN SWINE}, volume={70}, ISSN={["0021-8812"]}, DOI={10.2527/1992.703615x}, abstractNote={A study was conducted to examine effects of mating systems composed of natural service (NS) and AI in swine on farrowing rate, litter size, and labor requirements. Sows and gilts were bred once per day via one of the following treatments (d 1/d 2): NS/NS, NS/AI, AI/AI, and NS/none. Gilts bred with NS/AI, AI/AI, and NS/NS had higher (P less than .05) farrowing rates than gilts bred with NS/none matings. Similarly, farrowing rates were higher (P less than .05) in NS/AI than in NS/NS gilts. Numbers of pigs born alive were greater (P less than .05) in NS/NS, NS/AI, and AI/AI than in NS/none gilts. In sows, a treatment x time interaction (P less than .01) was present for farrowing rate. In the AI/AI treatment, farrowing rate increased (P less than .01) from 70.0% (wk 1 through 3) to 88.5% (wk 4 through 10). Farrowing rates were 87.3, 93.2, and 76.0% in the NS/NS, NS/AI, and NS/none groups, respectively, and did not change (P = .72) over time. Sows bred via NS/NS and NS/AI had larger litters (P less than .05) than NS/none sows. In the present study, if four or more sows and gilts were bred, then AI required less (P less than .05) time per animal than NS. Furthermore, gilts required more (P less than .05) time for breeding than sows. Results from this study demonstrate that gilts and sows responded differently to combinations of NS and AI in terms of reproductive performance. In addition, differences in labor requirements per sow or gilt between NS and AI matings were dependent on parity and daily breeding demands.}, number={3}, journal={JOURNAL OF ANIMAL SCIENCE}, author={FLOWERS, WL and ALHUSEN, HD}, year={1992}, month={Mar}, pages={615–621} }