MODULATION OF OVARIAN FOLLICLE MATURATION AND EFFECTS ON APOPTOTIC CELL-DEATH IN HOLTZMAN RATS EXPOSED TO 2,3,7,8-TETRACHLORODTBENZO-P-DIOXIN (TCDD) IN-UTERO AND LACTATIONALLY

Recent reports have described the reproduction-modulating and endocrin e-disrupting effects following exposure to toxic substances such as 2, 3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Herein, we set out (1) to de termine whether TCDD exposure exerts detrimental effects on follicle m aturation in the Holtzman rat ovary and (2) to determine whether the e ffects of TCDD are mediated in part via apoptotic cell death, In certa in species, dioxin exposure is correlated with reduced fecundity, redu ced ovulatory rate, an increased incidence of endometriosis, and vario us reproductive cancers, Although some of the effects of TCDD are medi ated via the hypothalamic-pituitary axis, direct effects on the ovary have also been observed, In the present study, an oral dose of 1 mu g TCDD/kg maternal body weight was administered on Day 15 of gestation, Female pups were sacrificed on postnatal Day 21/22, and the ovaries we re excised, fixed for histologic analysis, and analyzed in a double-bl ind paradigm. The analysis included a count and measurement and classi fication of preantral and antral follicles throughout the entire ovary , The contralateral ovary from each animal was analyzed for DNA fragme ntation indicative of apoptotic cell death, The results indicate that TCDD treatment significantly reduced the number of antral follicles in the size classes 50,000 to 74,999 mu m(2) and >100,000 mu m(2). We al so observed a reduction in the number of preantral follicles less than 50,000 mu m(2). No difference was observed in the degree of apoptotic cell death in antral (50,000 to >100,000 mu m(2)) and preantral folli cles (50,000 mu m(2) to >75,000 mu m(2)) between TCDD-treated and cont rol-treated tissues, These data support the hypothesis that TCDD resul ts in a diminution in the number of antral and preantral follicles of certain size classes in animals exposed during critical periods of dev elopment, but that apoptosis does not appear to be the underlying mech anism in these particular follicles, This does not preclude apoptosis occurring in pools of smaller precursor follicles. (C) 1998 Elsevier S cience Inc.