Effect of chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin in female rats on ovarian gene expression

Kelli E. Valdez, Zhanquan Shi, Alison Y. Ting, Brian K. Petroff

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The aryl hydrocarbon receptor (AHR) mediates the effects of many endocrine disruptors and contributes to the loss of fertility in polluted environments. Female rats exposed chronically to environmentally relevant doses of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) across their lifespan experience accelerated reproductive senescence preceded by ovarian endocrine disruption. The purpose of this study was to determine the changes in ovarian gene expression that accompany the loss of ovarian function caused by chronic exposure to TCDD. Beginning in utero, female Sprague-Dawley rats received TCDD (1, 5, 50, or 200 ng/kg-week; n = 4 per group) or vehicle weekly throughout their lifespan, and were sacrificed on diestrus just prior to loss of reproductive cyclicity at 11 months of age. Microarray analysis was used to determine differences in ovarian gene expression between control and TCDD-treated (200 ng/kg-week) animals. To confirm microarray results, real-time PCR was used to assess changes in gene expression among treatment groups. TCDD treatment decreased (p < 0.05) proestrus serum estradiol concentrations with no effect on serum progesterone. In ovaries from rats treated with 200 ng/kg-week TCDD compared to controls, 19 genes of known function were found to be up-regulated, while 31 ovarian genes were found to be down-regulated ≥1.5-fold (p ≤ 0.05). Gene expression of 17α-hydroxylase decreased following chronic TCDD treatment, suggesting the decrease in estradiol biosynthesis may be a consequence of decreased substrate. Taken together with past studies indicating a lack of effect on hypothalamus or pituitary function, the apparent regulation of key ovarian genes support the hypothesis that chronic TCDD exposure directly affects ovarian function.

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalReproductive Toxicology
Volume28
Issue number1
DOIs
StatePublished - Jul 1 2009

Keywords

  • Aryl hydrocarbon receptor
  • Menopause
  • Ovary
  • Rat

ASJC Scopus subject areas

  • Toxicology

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