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This Article Full Text Full Text (PDF) All Versions of this Article: 76/2/198    most recent biolreprod.106.053991v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shi, Z. Articles by Petroff, B. K. Search for Related Content PubMed PubMed Citation Articles by Shi, Z. Articles by Petroff, B. K. Agricola Articles by Shi, Z. Articles by Petroff, B. K.

Ovarian Endocrine Disruption Underlies Premature Reproductive Senescence Following Environmentally Relevant Chronic Exposure to the Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-Dioxin¹

Center for Reproductive Sciences³ and Departments of Internal Medicine⁴ and Molecular and Integrative Physiology,⁵ University of Kansas Medical Center, Kansas City, Kansas 66160 Department of Animal Physiology,⁶ University of Warmia and Mazury in Olsztyn, Olsztyn 10-718, Poland

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.

aging, aryl hydrocarbon receptor, estradiol, menopause, ovary, pituitary, rat, reproduction, toxicology

¹Supported by the United States National Institutes of Health (NIH/NIEHS ES012916, to B.K.P.), the NIH Center for Reproductive Sciences, the University of Kansas Medical Center, and the University of Virginia NIH Center for Research in Reproduction Ligand Analysis Core.

Correspondence: ²Brian K. Petroff, Center for Reproductive Sciences, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160. FAX: 913 588 7180; e-mail: bpetroff{at}kumc.edu