Endocrine-disrupting chemicals alter embryonic brain development and adult neurobehavioral phenotypes

Endocrine-disrupting chemicals are detectable in nearly every environment on the planet. Humans and wildlife are exposed to myriad of these pollutants throughout their life. Because these chemicals interfere with hormone systems in the body, exposure to them during early life development can have a severe impact on later neurobiological and reproductive health. In this dissertation, I investigated how prenatal exposure to two specific EDCs affected the organization of the embryonic brain and changed neuromolecular and behavioral phenotypes in adulthood. The weakly estrogenic mixture of polychlorinated biphenyls (PCBs), Aroclor 1221 (A1221), and the antiandrogenic fungicide vinclozolin (VIN) offer insight through their different mechanisms of interrupting normal endocrine function. I hypothesized that these chemicals would affect the brain and behavior of adult rats in a sex- and compound-specific manner. The first study in this dissertation demonstrates that prenatal exposure to these EDCs can disrupt an important sociosexual behavior in adult rats together with changes in the patterns of expression of associated genes. More specifically, in a test of sociosexual preference, adult rats failed to demonstrate the sex-typical preference for a mate after prenatal exposure to PCBs or VIN in males, and PCBs in females. The second study extends the previous findings by probing for deficits in the ability to distinguish between and/or prefer odorants that convey information about a mate’s fitness, i.e., hormonal status. I deduced that while changes to odor preference strongly resemble the mate preference phenotype, odor discrimination ability is not impaired. However, the activation of the ventrolateral portion of the ventromedial nucleus, a brain region known to regulate mate preference behavior, was altered by PCB exposure in females, suggesting that improper central processing of odor signals may explain some of the results. In the third study, I found that PCB exposure shifted the timing of the hormone-sensitive process of embryonic neurogenesis in the ventromedial nucleus but not the preoptic area. Taken together, these studies demonstrate a possible mechanism by which an EDC can change brain organization and functionally transfer the effects of a prenatal exposure into adulthood.