Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the reproductive system in the rat

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disruptor. As such, it is a potent reproductive toxicant. The current studies were undertaken in order to determine the loci at which TCDD exerts its effects. Initial studies indicated that in-utero and lactational exposure to TCDD caused a reduction in the number of antral follicles in size classes 50,000–74,000 μm2 and >100,000 μm 2 and preantral follicles <50,000 μm2 in the ovary and reduced serum estrogen concentrations. A reduction in healthy ovarian follicle number would likely reduce reproductive function. It is possible that this effect could be the result of direct actions at the ovary or due to indirect actions via altered hypothalmic and/or pituitary function. The effects of TODD are mediated via the aromatic hydrocarbon receptor (AhR) and the AhR nuclear translocator (ARNT). AhR and ARNT mRNA and protein concentrations were quantified across the four-day estrous cycle. We found that the levels of these molecules were not regulated by the estrous cycle. These data indicate that the ovary is a potential site of TCDD-induced toxicity but that the sensitivity of the ovary does not vary across the estrous cycle. Since ovarian function is modulated by the hypothalamus and the anterior pituitary, we investigated whether TCDD could alter hormone release from those glands in vitro . TCDD had no effect on gonadotropin-releasing hormone (GnRH) release from the hypothalamus in vitro as there were no differences in the average peak interval between pulses, average peak amplitude or baseline GnRH release. TCDD also exerted no effect on GnRH-induced release of follicle-stimulating hormone or luteinizing hormone from the pituitary in vitro as there were no differences in peak amplitude of gonadotropin release or baseline release. Further, TCDD had no effect on AhR, ARNT or estrogen receptor α mRNA populations within the pituitary. These findings suggest that the ovary is the primary target for the disruptive effects of TODD to the female reproductive system in the rat. These findings do not preclude other deleterious effects at the other loci within the reproductive system of the rat.