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Alterations to Maternal Behavior and Brain by Exogenous Estrogen Exposure

Maternal care is critical for the development and long-term success of offspring. Poor maternal care can have profound effects on offspring that can last into adult life. Despite our understanding of the role of endogenous estrogen in maternal behavior, the potential effects of exogenous estrogens (xenoestrogens) on maternal behavior and brain remain poorly understood. The active synthetic estrogen in contraceptive pills, 17α-ethinyl estradiol (EE2), is widely used as a positive control for estrogenicity in endocrinology and toxicology studies. Another xenoestrogen, bisphenol A (BPA) alters a broad range of physiological processes including neural development and reproduction. Due to public health concerns with BPA, alternative compounds have been developed for use in consumer products. One replacement, bisphenol S (BPS), has not been examined extensively, but has shown estrogenic properties. Biomonitoring studies indicate that human exposures to BPS are likely to be widespread. Among studies that have reported effects of endocrine disruptors on maternal behavior, none have concurrently examined effects on the regions of the brain important to maternal behaviors. Thus, one of the major goals of this dissertation sought to address this gap in current knowledge. We hypothesized that low doses of two xenoestrogens, EE2 and BPS, would disrupt maternal behavior and affect regions of the brain important for maternal behavior. We further hypothesized that neurogenesis might be one of the critical mechanisms underlying estrogen regulated maternal behavior and that xenoestrogen exposures during pregnancy induce alterations to neurogenesis. We investigated the effects of low dose exogenous estrogens on mice during pregnancy and lactation (the F0 generation), and on females exposed during gestation and the perinatal period (the F1 generation). The work summarized in this dissertation indicates that low doses of the synthetic estrogens EE2 and BPS alter aspects of behavior and brain in pregnant/lactating females, providing evidence that adults are susceptible to the disruptive effects of these compounds during these vulnerable periods. Our findings also suggest that females are vulnerable to exposures during gestation/perinatal development, and these exposures are sufficient to influence the display of maternal behavior later in life. Finally, our results indicate that neurogenesis can be disrupted by xenoestrogen exposures.