2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), one of the key endocrine disruptors, has been shown to cause reproductive and developmental disorders. Our previous studies have primarily focused on TCDD induced impairment of ovarian follicular development in female F1 rats. It is unknown whether TCDD exposure will interfere with follicular development by altering mRNA expression of anti-Müllerian hormone (AMH) and AMH receptor type II (AMHR2) in the ovary. In the present study, pregnant Sprague Dawley rats were treated with TCDD (100 or 500 ng/kg body weight) dissolved in a corn oil vehicle by gavage from gavage from gestational days (GD) 8-14, while the control group received solely corn oil. The F1 rats were mated with unexposed males for the F2 generation, while another portion of the female offspring (F2) were mated for the F3 generation. Serum AMH levels and ovarian AMH/AMHR2 mRNA expression in the adult female offspring (F1, F2 and F3 generations) were measured. Follicle count and granulosa cell apoptosis were evaluated in the F2 and F3 generations. The results showed that in the F2 generation, TCDD exposure affected the number of primordial follicles, secondary follicles, and corpora lutea. It also increased serum AMH concentration and the apoptosis rate of granulosa cells. These results might be associated with the upregulation of AMH/AMHR2 mRNA expression in the ovary. In conclusion, TCDD exposure reduced the ovarian reserve in rats and inhibited follicular development in adult female offspring, an effect that persisted for multiple generations. The altered AMH and AMHR2 mRNA expression may contribute to the observed adverse effects.
Keywords: 2,3,7,8-Tetrachlorodibenzo-p-dioxin; Anti-Müllerian hormone; Multigenerational; Ovarian impairment; Transgenerational.
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