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This Article Full Text Full Text (PDF) All Versions of this Article: 74/1/125    most recent biolreprod.105.044396v1 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 Franczak, A. Articles by Petroff, B. K. Search for Related Content PubMed PubMed Citation Articles by Franczak, A. Articles by Petroff, B. K. Agricola Articles by Franczak, A. Articles by Petroff, B. K.

Effects of Acute and Chronic Exposure to the Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the Transition to Reproductive Senescence in Female Sprague-Dawley Rats¹

Center for Reproductive Sciences³ Department of Internal Medicine,⁴ University of Kansas Medical Center, Kansas City, Kansas 66160 Department of Animal Physiology,⁵ University of Warmia and Mazury, 10-718 Olsztyn, Poland Department of Pharmacology,⁶ Kansas City University of Medicine and Biosciences, Kansas City, Missouri 64106

ABSTRACT

Activation of the aryl hydrocarbon receptor (AHR) can occur in polluted environments, either from smoking-related toxicants or from endogenous ligands. We tested whether acute or chronic exposure to the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the transition to reproductive senescence in female Sprague-Dawley rats. In experiment 1, rats (n = 6 per experimental group) received a single dose of 0 or 10 µg/kg of TCDD orally (p.o.) on Postnatal Day 29. Vaginal cytology was monitored for 1 wk each month until rats were killed at 1 yr of age. The single prepubertal exposure to TCDD hastened the transition to reproductive senescence in female rats and was associated with delayed puberty, abnormal cyclicity, and premature reproductive senescence. In a second experiment, rats were exposed to TCDD chronically through weekly dosing (0, 50, or 200 ng kg^–1 wk^–1 p.o., n = 7 each dose) beginning in utero. Lifelong exposure to these lower doses of TCDD induced a dose- and time-dependent loss of normal cyclicity and significantly hastened the onset of the transition to reproductive senescence (P < 0.05). This premature transition to reproductive senescence was associated with prolonged estrous cycles and, at the highest dose of TCDD, persistent estrus or diestrus. The number and size of ovarian follicles were not altered by TCDD. Diestrous concentrations of LH in rats exposed chronically to TCDD were similar to those in controls, whereas progesterone tended to be elevated at both doses of the dioxin (P < 0.08). Serum FSH was elevated in the group exposed to 50 ng/kg of TCDD (P < 0.02), whereas estradiol was decreased at both doses of dioxin (P < 0.01). Data thus far support endocrine disruption rather than depletion of follicular reserves as a primary mechanism of the premature transition to reproductive senescence following activation of the AHR pathway by TCDD in female rats.

aging, environment, estradiol, ovulatory cycle, toxicology

¹ Supported in part by the Kansas City Area Life Sciences Initiative, NICHD HD28934 and NIEHS ES012916.

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