Modulation by environmental toxicants of the female reproductive system

Many man-made toxicants persist in the environment and are capable of disrupting reproduction and development. The general goals of this dissertation project were (1) to elucidate the impact of environmental toxicants on the mammalian ovary; and (2) to examine the mechanisms by which these toxicants exert their effects. To answer these questions, a three-part study was designed. Parts I and II determined (1) whether an in-utero and lactational exposure to ammonium perchlorate (AP) or a polychlorinated biphenyl (PCB) mixture exerts detrimental effect on ovarian follicle maturation in rat; and (2) whether the effects of the chemicals were attenuated by thyroid hormone supplementation. The data support the hypothesis that AP and PCBs reduce the number of ovarian follicles in rats exposed during the critical period of development, and that thyroid hormone supplementation can circumvent some of the effects. Since previous research in our lab strongly supports a local role for the interplay between the E2- and AHR-signaling systems in the primate ovary, Part III investigated intra-ovarian localization of the dioxin receptor (aromatic hydrocarbon receptor, AHR) in the rhesus monkey (Macaca mulatta) ovary. A definitive localization of the AHR further enhanced our understanding of the potential effects of environmental pollutants on reproductive function in primates.; Females, during their reproductive years, are constantly exposed via their surrounding environment to contaminants that disrupt their hormonal systems. Physiologic effects of these "endocrine-disrupting" toxins include perturbations in thyroid function, morphologic anomalies, reduced fecundity, modulation of ovarian steroidogenesis and follicular development, and carcinogenicity that can result in direct and indirect impacts on reproductive success. For this reason, we developed a research paradigm that focused on uncovering mechanisms by which some of these environmental toxins modulate the mammalian ovary.; The significance of this kind of research is far-reaching. Information obtained from the studies described herein and future studies are expected to enhance our understanding of the consequences to female reproductive health. By taking responsibility for contamination of "our environment", we hope to lead the way to (1) understanding the mechanism(s) by which environmental pollutants impact a woman's ovary; and (2) finding ways to circumvent or cure these deleterious effects for the improvement of female reproductive health.