Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits at the hypothalamus-pituitary-gonadal axis of CD-1 mice

Wei XI, C. K. F. LEE, W. S. B. YEUNG, John P. GIESY, Ming Hung WONG, Xiaowei ZHANG, Markus HECKER, Chris K. C. WONG

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Abstract

Bisphenol A (BPA) is used in the manufacture of many products and is ubiquitous in the environment. Adverse effects of BPA on animal reproductive health have been reported, however most of the studies relied on the approaches in the assessment of conventional histology and anatomical features. The mechanistic actions of BPA are not clear. In the present study, a murine model was used to study potential effects of BPA exposure during perinatal and postnatal periods on endocrine functions of hypothalamic-pituitary-gonadal (HPG)-axis. At the hypothalamic-pituitary level, BPA exposure resulted in the up-regulation of the expression levels of KiSS-1, GnRH and FSH mRNA in both male and female pups. At the gonadal levels, BPA caused inhibition in the expressions of testicular steroidogenic enzymes and the synthesis of testosterone in the male pups. Conversely exposure to BPA resulted in a greater aromatase expression level and the synthesis of estrogen in the female pups. BPA is a weak estrogen agonist and its effects reported on animal studies are difficult to reconcile with mechanistic action of estrogen. In this study we hypothesized that the effects of BPA on reproductive dysfunction may be due to its actions on gonadal steroidogenesis and so the anomalous releases of endogenous steroid hormones. This non-ER-mediated effect is more potent in affecting the feedback regulatory circuits in the HPG-axis. Copyright © 2010 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)409-417
JournalReproductive Toxicology
Volume31
Issue number4
DOIs
Publication statusPublished - May 2011

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Hypothalamus
Networks (circuits)
Estrogens
Animals
Steroid hormones
bisphenol A
Histology
Aromatase
Reproductive Health
Gonadotropin-Releasing Hormone
Testosterone
Up-Regulation
Steroids
Health
Hormones
Feedback
Messenger RNA
Enzymes

Citation

Xi, W., Lee, C. K. F., Yeung, W. S. B., Giesy, J. P., Wong, M. H., Zhang, X., . . . Wong, C. K. C. (2011). Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits at the hypothalamus-pituitary-gonadal axis of CD-1 mice. Reproductive Toxicology, 31(4), 409-417. doi: 10.1016/j.reprotox.2010.12.002

Keywords

  • Kisspeptin
  • GPR-54
  • Gonadotrophin
  • Steroidogenesis