The effects of prenatal PCBs on female reproduction: Development, behavior, and gene expression.

摘要

Polychlorinated biphenyls (PCBs) are a class of bioactive chemical once used in industrial applications, but which now contaminate the world environment. PCBs are lipophilic with few natural degadatory mechanisms, and thus they accumulate in human and animal tissues, and are passed to subsequent generations via transfer between mother and offspring. Research has shown that PCBs can interfere with brain and sexual organ development, and adult sexual behaviors and reproduction. However, previous studies produced contradictory results based on the dose and method of administration, species, and the age at exposure. The research detailed in this thesis elucidates the effects of prenatal exposure to low levels of a commercial mixture of PCBs, Aroclor (A) 1221, on female reproductive function.; The studies undertaken in this dissertation focus on three areas relevant to understanding long-term effects of PCBs on reproductive physiology in female rats: (1) developmental effects in two generations, (2) sexual behaviors in the first generation, and (3) gene expression in the first generation. In the first research section of this dissertation, the sexual and somatic development of PCB-exposed animals is investigated in first (F1) and second (F2) generation females. Dose-dependent effects are observed in both generations, and a greater number of endpoints are significantly affected in the F2, including circulating hormone levels and uterine and ovarian weight. The second research section of the dissertation explores whether sexual behaviors in the first generation of exposed animals are altered by A1221, using a paced mating paradigm designed to elucidate female-typical behaviors. Several salient behaviors are affected by PCB exposure, including likelihood to mate, mating trial pacing, and stress-related vocalizations. The third research chapter discusses the results of a genome-wide microarray assay performed on the preoptic area of the brain. The preoptic area is a neuroendocrine control center implicated in regulation of reproductive physiology and behavior. Taken together, these results suggest that A1221 has long lasting and trans-generational effects on the development and behavior of exposed females, accompanied by altered gene expression in a neuroendocrine region of the brain. These findings have implications for female reproductive health and reproductive success in wildlife and humans.