2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1. nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48. h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48. h. TCDD, however, did down regulate the AHR protein at 48. h. TCDD exposure for 96. h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96. h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down-regulation of the AHR protein in TCDD exposed follicles persisted at 96. h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles.
|Number of pages||12|
|Journal||Toxicology and Applied Pharmacology|
|State||Published - Oct 1 2012|
Bibliographical noteFunding Information:
This work was supported by NIH R01 HD 047275 , NIH R01 ES 019178 (JAF), NIEHS ES07326 Research Training Program in Endocrine, Developmental and Reproductive Toxicology (BNK), and an Environmental Toxicology Predoctoral Fellowship (MSB). The authors would also like to thank Liying Gao, Dr. Zelieann R. Craig, Dr. Wei Wang, Dr. Tessie Palouse, and Ayelet Ziv Gal for their technical assistance in isolating antral follicles.
- Antral follicle
- Aryl hydrocarbon receptor
ASJC Scopus subject areas