Developmental programming: impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus.

Toxicology and Applied Pharmacology
Megan M Mahoney, V Padmanabhan

Abstract

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5mg/kg/day) from day 30 to 90 of gestation (term 147d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F(2alpha), just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal ...Continue Reading

Citations

Feb 19, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Arunoday BhanSubhrangsu S Mandal
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Mar 5, 2013·Toxicology and Applied Pharmacology·Bachir Abi SalloumVasantha Padmanabhan
Nov 4, 2015·Reproductive Toxicology·Rodrigo Fernandes de LimaFernanda Cristina Alcantara Santos
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Jun 25, 2014·Environmental Science & Technology·Daniel M RotroffRichard S Judson

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