SFEBES2022 Cutting Edge Session Endocrinology in a Warming Dirty World (3 abstracts)
The University of Texas at Austin, Austin, Texas, USA
Environmental endocrine-disrupting chemicals (EDCs) are exogenous chemicals that perturb hormones and their actions. In our laboratory, we are studying how early life exposures to EDCs affect the developing brain and lead to behavioral dysfunctions in exposed individuals and their descendants across generations. To do this, pregnant rats are fed one of three treatments: the weakly estrogenic commercial polychlorinated biphenyl (PCB) mixture, Aroclor 1221 (A1221, 1 mg/kg); vinclozolin (VIN, 1 mg/kg), a fungicide with anti-androgenic properties; or the vehicle (3% DMSO in sesame oil). We monitor birth outcomes and postnatal development in female and male offspring. In adulthood, animals are run through a battery of behavioral tests to assess functional neurobiological changes. The brains of these rats are subsequently used to identify molecular and cellular changes underlying the behavioral phenotype. For multigenerational work, rats are bred to the F3 generation, which have no direct exposure to EDCs, in order to assess transgenerational epigenetic inheritance. Results show that directly exposed (F1 generation) rats exhibit sex-specific alterations in social, sociosexual, and anxiety-like behaviors. Gene-expression profiling of brains from these animals has identified suites of genes differentially affected by the EDCs compared to vehicle rats. From the transgenerational studies we find that social and anxiety-like behaviors are altered in a sex-specific manner, and that the lineage from which the F3 rats descend (paternal or maternal) plays a key role in outcomes, potentially due to differences in epigenetic programming of the germline between males and females. Current research seeks to determine how epigenetic marks may be retained across generations and lead to a behavioral phenotype. As a whole, this body of work indicates that gestational exposure to EDCs has life-long effects on the developing brain, neuroendocrine systems, and reproductive and social behaviors of exposed individuals, and their descendants. (Supported by NIH ES029464).