Endocrine disruptors and hormonally-sensitive windows across the life cycle of females

Endocrine-disrupting chemicals (EDCs) pose serious threats to women’s health. Deleterious effects of EDC exposure early development, particularly during hormonally-sensitive windows, are well documented in longitudinal studies, demonstrating that effects are often “hidden” until adulthood. However, exposures rarely occur once, and EDCs are not the only neuroendocrine challenge one faces over the life course. Interactions between EDC exposures and other stressors are less understood. The first two experimental chapters of this dissertation focused on perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic mixture well-established endocrine disruptors called polychlorinated biphenyls (PCBs), and peripubertal sociosexual stress using the sexual conspecific aggressive response (SCAR) model using a 2x2 design. These stressors were hypothesized to interact: SCAR was expected to exacerbate or “unmask” A1221 exposure effects in adult female rats. Experiments did not show any interactions between A1221 and SCAR, treatments exerted independent effects. In the first study, neither treatment appeared to elicit depressive-like behavioral phenotypes, but rats exposed to A1221 exhibited dexamethasone (dex) nonsuppression during a dexamethasone suppression test (DST). In the second study, SCAR exerted anxiolytic effects during open field testing. In this study, SCAR experience was paired with an odor cue, and when experimental animals were assessed for odor preference, rats that underwent SCAR tended to show a stronger preference for the odor cue. At euthanasia (~P85), there were no group differences in cytochrome c oxidase (COX) in the paraventricular nucleus (PVN) of the hypothalamus, basolateral amygdala (BLA), or ventrolateral area of the ventromedial nucleus of the hypothalamus (VMNvl), and A1221-exposed animals tended to have lower circulating corticosterone (CORT). Results suggested that, in female rats, SCAR does not elicit a stressed phenotype, perinatal A1221 exposure perturbs stress reactivity, and treatments are not associated with changes in metabolism in brain. The fourth chapter of this dissertation is a systematic literature review and meta-analysis that investigated whether EDC exposure predisposes pregnant women to peripartum depression (PPD). Pregnancy is another hormonally-sensitive window that is under researched. Results demonstrated that EDC exposures increase the odds of pregnant women developing PPD, and this is an understudied and emerging research question.