Ovarian endocrine disruption underlies premature reproductive senescence following environmentally relevant chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin

Zhanquan Shi, Kelli E. Valdez, Alison Y. Ting, Anita Franczak, Steve L. Gum, Brian K. Petroff

Research output: Contribution to journalArticlepeer-review

57 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. While previous work has focused on mechanisms of short-term endocrine disruption and ovotoxicity in response to AHR ligands, we have shown recently that chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces premature reproductive senescence in female rats without depletion of ovarian follicular reserves. In the current study, premature reproductive senescence was induced using a range of low-dose exposure to TCDD (0, 1, 5, 50, and 200 ng kg -1 wk-1) beginning in utero and continuing until the transition to reproductive senescence. Doses of 50 and 200 ng TCDD kg -1 wk-1 delayed the age at vaginal opening and accelerated the loss of normal reproductive cyclicity with age without depletion of follicular reserves. Serum estradiol concentrations were decreased in a dose-dependent fashion (≥5 ng kg-1 wk-1) across the estrous cycle in perisenescent rats still displaying normal cyclic vaginal cytology. Serum FSH, LH, and progesterone profiles were unchanged by TCDD. The loss of reproductive cyclicity following chronic exposure to TCDD was not accompanied by decreased responsiveness to GnRH. Ovarian endocrine disruption is the predominant functional change preceding the premature reproductive senescence induced by chronic exposure to low doses of the AHR-specific ligand TCDD.

Original languageEnglish (US)
Pages (from-to)198-202
Number of pages5
JournalBiology of reproduction
Volume76
Issue number2
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

Keywords

  • Aging
  • Aryl hydrocarbon receptor
  • Estradiol
  • Menopause
  • Ovary
  • Pituitary
  • Rat
  • Reproduction
  • Toxicology

ASJC Scopus subject areas

  • Reproductive Medicine

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