EDCs Reorganize Brain-Behavior Phenotypic Relationships in Rats

Abstract

All species, including humans, are exposed to endocrine-disrupting chemicals (EDCs). Previous experiments have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs [polychlorinated biphenyls (PCB), vinclozolin (VIN)], or vehicle. In adulthood, a sociosexual preference test was administered. We profiled gene expression of in preoptic area (POA), medial amygdala (MeA), and ventromedial nucleus (VMN). Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region had unique sets of genes altered in a sex- and EDC-specific manner. Effects of EDCs on individual traits were typically small, but robust; EDC exposure changed the relationships between gene expression and behavior, a pattern we refer to as dis-integration and reconstitution. These findings underscore the effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of genes and behavior after prenatal exposure to EDCs.

Early Female Transgender Identity after Prenatal Exposure to Diethylstilbestrol: Report from a French National Diethylstilbestrol (DES) Cohort

“…Although research in the transgender field is increasing, the causal mechanisms have not been adequately identified yet [ 13 , 37 ]. Genetic [ 38 , 39 ], biological [ 1 , 4 ], anatomical [ 40 , 41 ] and environmental factors [ 42 , 43 ] have mainly been studied. A greater chance of transgender concordance among XY monozygotic tweens than dizygotic tweens [ 44 ] supports a genetic component.…”

“…In many animal studies, EDC exposure during development has been associated with changes in sex behavior, such as disruption of the normal social preference behavior (rats) and alteration of the differentiation of relevant sexually dimorphic pathways (mouse, Japanese quail) [ 42 , 43 ]. The most convincing evidence linking testosterone to the establishment of the male gender identity comes from individuals with DSDs, such as XY complete androgen insensitivity syndrome [ 45 ], XY 5 alpha reductase deficiency [ 46 ] and XX congenital adrenal hyperplasia (CAH) [ 47 ].…”

Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

“…In the current study, we designed a mixture comprising bisphenols, phthalates, perfluorinated, polybrominated and polychlorinated compounds, and vinclozolin. Their selection for the NeuroMix was based on evidence showing that each chemical individually causes deficits in behaviors and/or changes in neurobiological markers in animals [ 5 , 6 , 19 , 63 , 64 , 65 , 66 ] and is detectable in humans [ 30 , 32 , 67 , 68 , 69 , 70 , 71 , 72 ]. This current study adds to the literature by using these chemicals in combination at human-relevant dosages and administered by the most relevant (oral) route.…”

Environmental Health and Toxicology: Immunomodulation Promoted by Endocrine-Disrupting Chemical Tributyltin

“…Moreover, to the date of this publication, there are also no data comparing immunological alterations in males and females exposed to TBT. Evidence for divergence in responses between both sexes has already been shown for other endocrine disruptors, such as bisphenols [ 133 ] and even for TBT, but this was in the context of the nervous system [ 134 ].…”