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Developmental programming: impact of prenatal exposure to bisphenol-A and methoxychlor on steroid feedbacks in sheep.

Abstract：

:Bisphenol-A (BPA), a polymer used in plastics manufacturing, and methoxychlor (MXC), a pesticide, are endocrine disrupting compounds with estrogenic and anti-androgenic properties. Prenatal BPA or MXC treatment induces reproductive defects in sheep with BPA causing prepubertal luteinizing hormone (LH) hypersecretion and dampening of periovulatory LH surges and MXC lengthening follicular phase and delaying the LH surge. In this study, we addressed the underlying neuroendocrine defects by testing the following hypotheses: 1) prenatal BPA, but not MXC reduces sensitivity to estradiol and progesterone negative feedback, 2) prenatal BPA, but not MXC increases pituitary responsiveness to gonadotropin releasing hormone (GnRH), and 3) prenatal BPA dampens LH surge response to estradiol positive feedback challenge while prenatal MXC delays the timing of the LH surge. Pregnant sheep were treated with either 1) 5mg/kg/day BPA (produces approximately twice the level found in human circulation, n=8), 2) 5mg/kg/day MXC (the lowest observed effect level stated in the EPA National Toxicology Program's Report; n=6), or 3) vehicle (cotton seed oil: C: n=6) from days 30 to 90 of gestation. Female offspring of these ewes were ovariectomized at 21months of age and tested for progesterone negative, estradiol negative, estradiol positive feedback sensitivities and pituitary responsiveness to GnRH. Results revealed that sensitivity to all 3 feedbacks as well as pituitary responsiveness to GnRH were not altered by either of the prenatal treatments. These findings suggest that the postpubertal reproductive defects seen in these animals may have stemmed from ovarian defects and the steroidal signals emanating from them.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Abi Salloum B,Steckler TL,Herkimer C,Lee JS,Padmanabhan V

doi

10.1016/j.taap.2013.02.011

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

300-8

issue

3

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(13)00081-1

journal_volume

268

pub_type

杂志文章

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