2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) blocks ovulation by a direct action on the ovary without alteration of ovarian steroidogenesis: lack of a direct effect on ovarian granulosa and thecal-interstitial cell steroidogenesis in vitro

The main purpose of this study was to investigate the direct effect of 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) on ovarian function including ovulat ion and steroidogenesis. In vivo effects of TCDD were investigated on ovula tion and alteration of circulating and ovarian steroid hormones in immature hypophysectomized rats (IHR) primed with equine chorionic gonadotropin (eC G) and human chorionic gonadotropin (hCG). In addition, in vitro effects of TCDD on the steroidogenesis of granulosa cells (GC), theca-interstitial ce lls (TIC), and whole ovarian dispersates derived from the ovary of IHR were investigated. In the ovulation model, rats were hypophysectomized on Day 2 3 of age. On Day 26, the IHR were given 20 mu g TCDD/kg by gavage. The next day eCG (10 IU) was injected sc to stimulate follicular development. Fifty -two hours after eCG, 10 IU hCG was given to induce ovulation. TCDD (20 mu g/kg) blocked ovulation and reduced ovarian weight in IHR. Concentrations o f progesterone (P4), androstenedione (A4), and estradiol (E2) in sera and o varies were not altered by TCDD at 12, 24, 48, and 72 h after eCG, except f or a two-fold increase in ovarian concentration of A4 at 48 h after TCDD. H owever, this higher concentration of A4 at 48 h after TCDD did not reflect that of A4 in sera and did not correlate with E2 in either sera or ovaries. In isolated GC from untreated IHR, TCDD (0.1 to 100 nM) had no significant effect on P4 and E2 after stimulation by LH or FSH. In TIC and whole ovari an dispersates containing GC, TIC, and other ovarian cells, TCDD (0.1 to 80 0 nM) had no effect on A4 and P4 secretion stimulated by LH. Using RT-PCR, AhR mRNA was shown to be expressed constitutively in the whole ovary of IHR with maximum down-regulation at 6 h after TCDD (20 mu g/kg). Ovarian CYP1A 1 was induced maximally at 6 h after TCDD, whereas CYP1B1 could not be dete cted. The induction of AhR related genes by TCDD in the ovary implies the e xistence of AhR-mediated signal transduction pathways. In summary, these re sults indicate that TCDD does not affect ovulation in IHR by altering ovari an steroidogenesis. It seems that inhibition of ovulation by TCDD is due to processes related to follicular rupture. (C) 1999 Elsevier Science Inc. Al l rights reserved.