PARENT SESSION

(W231) CHRONIC EXPOSURE TO THE ARYL HYDROCARBON RECEPTOR AGONIST 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ACCELERATES REPRODUCTIVE SENESCENCE IN THE FEMALE RAT.

Petroff, Brian¹, Franczak, Anita^{1, 2}, Valdez, Kelli¹, Mizinga, Kemmy¹, ¹ University of Kansas Medical Center, Kansas City, KS² University of Warmia and Mazury, Olsztyn, Poland

ABSTRACT- Chronic activation of the aryl hydrocarbon receptor (AhR) can occur in polluted environments or from smoking-related toxicants. In the current study, female Sprague Dawley rats were exposed to the potent AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through weekly dosing (0, 1, 50, 200 ng/kg/wk p.o.). Dams were dosed during pregnancy and lactation (gestation days 14 and 21, days 7 and 14 postnatal) and pups were treated directly thereafter. Reproductive cyclicity was assessed for one week each month through cytologic examination of daily vaginal smears. Rats were sacrificed once the onset of the transition to reproductive senescence was evident in TCDD-treated rats at 10 months. The onset of a prolonged (≥6 days) interestrus interval was considered evidence of the transition to reproductive senescence. Rats were sacrificed on the morning of diestrus once TCDD-treated animals had exhibited a transition to reproductive senescence and trunk blood and ovaries were collected. TCDD induced a dose and time-dependent loss of normal cyclicity and significantly hastened reproductive senescence (p ≤ 0.05). The premature transition to reproductive senescence in TCDD-treated rats was associated with prolonged estrous cycles and both persistent estrus and diestrus at the highest dose. The number and size distribution of ovarian follicles were not altered by TCDD. Diestrous concentrations of progesterone tended (p ≤ 0.09) to be elevated in animals receiving the two highest doses of the dioxin. There was no consistent effect of TCDD on FSH or LH concentrations at diestrus although FSH was elevated (p ≤ 0.008) vs. controls for the 50 ng/kg group. These results suggest that chronic exposure to toxicants that activate the AhR can hasten the loss of reproductive function with age in the female. Data thus far support endocrine disruption rather than depletion of follicular reserves as a primary mechanism of the premature transition to female reproductive senescence following chronic activation of the aryl hydrocarbon receptor pathway by TCDD in rats. This work was supported in part by the Kansas City Area Life Sciences Institute, NICHD HD28934 and NIEHS ES012916.

KEY WORDS: environment, female, endocrinology, aging