@misc{bateman_patisaul_2008, title={Disrupted female reproductive physiology following neonatal exposure to phytoestrogens or estrogen specific ligands is associated with decreased GnRH activation and kisspeptin fiber density in the hypothalamus}, volume={29}, ISSN={["1872-9711"]}, DOI={10.1016/j.neuro.2008.06.008}, abstractNote={It is well established that estrogen administration during neonatal development can advance pubertal onset and prevent the maintenance of regular estrous cycles in female rats. This treatment paradigm also eliminates the preovulatory rise of gonadotropin releasing hormone (GnRH). It remains unclear, however, through which of the two primary forms of the estrogen receptor (ERα or ERβ) this effect is mediated. It is also unclear whether endocrine disrupting compounds (EDCs) can produce similar effects. Here we compared the effect of neonatal exposure to estradiol benzoate (EB), the ERα specific agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), the ERβ specific agonist diarylpropionitrile (DPN) and the naturally occurring EDCs genistein (GEN) and equol (EQ) on pubertal onset, estrous cyclicity, GnRH activation, and kisspeptin content in the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei. Vaginal opening was significantly advanced by EB and GEN. By 10 weeks post-puberty, irregular estrous cycles were observed in all groups except the control group. GnRH activation, as measured by the percentage of immunopositive GnRH neurons that were also immunopositive for Fos, was significantly lower in all treatment groups except the DPN group compared to the control group. GnRH activation was absent in the PPT group. These data suggest that neonatal exposure to EDCs can suppress GnRH activity in adulthood, and that ERα plays a pivotal role in this process. Kisspeptins (KISS) have recently been characterized to be potent stimulators of GnRH secretion. Therefore we quantified the density of KISS immunolabeled fibers in the AVPV and ARC. In the AVPV, KISS fiber density was significantly lower in the EB and GEN groups compared to the control group but only in the EB and PPT groups in the ARC. The data suggest that decreased stimulation of GnRH neurons by KISS could be a mechanism by which EDCs can impair female reproductive function.}, number={6}, journal={NEUROTOXICOLOGY}, author={Bateman, Heather L. and Patisaul, Heather B.}, year={2008}, month={Nov}, pages={988–997} }
 @article{patisaul_bateman_2008, title={Neonatal exposure to endocrine active compounds or an ERβ agonist increases adult anxiety and aggression in gonadally intact male rats}, volume={53}, ISSN={0018-506X}, url={http://dx.doi.org/10.1016/j.yhbeh.2008.01.008}, DOI={10.1016/j.yhbeh.2008.01.008}, abstractNote={Endocrine active compounds (EACs) have been shown to influence a number of reproductive endpoints but less is known about how they might affect other hormone dependent behaviors including anxiety and aggression. Recent evidence suggests that these effects may be mediated through the beta form of the estrogen receptor (ERβ). Using male Long Evans rats, we sought to determine how neonatal exposure to EACs affects anxiety and aggression in adulthood. Anxiety was assessed using the elevated plus maze and aggression was assessed 8weeks later using the resident intruder test. To gain insight into which ER subtype (ERα vs ERβ) might be mediating these effects we used agonists specific for ERα (1,3,5-tris(4-Hydroxyphenyl)-4-propyl-1H-pyrazole (PPT)) or ERβ (Diarylpropionitrile (DPN)) as additional treatment groups. For these experiments the synthetic EAC bisphenol-A (BPA) and the phytoestrogen metabolite equol (EQ) were used. Male neonates were injected with either 0.05 ml sesame oil (control), 50 μg estradiol benzoate (EB), 1 mg/kg DPN, 1 mg/kg PPT, 50 μg/kg BPA, or 10 mg/kg EQ daily for 4 days beginning on the day of birth (PND 0). Compared to the oil treated controls, significantly fewer open arm entries were made by the males neonatally treated with DPN, EQ, or BPA. The DPN and EQ treated males were also more aggressive compared to the controls. These findings suggest that neonatal exposure to EACs with agonistic activity on ERβ may influence affective behavior in adulthood, including anxiety and aggression.}, number={4}, journal={Hormones and Behavior}, publisher={Elsevier BV}, author={Patisaul, Heather B. and Bateman, Heather L.}, year={2008}, month={Apr}, pages={580–588} }