Direct, multi- and transgenerational effects of endocrine disruptors on maternal behavior and female sexual maturation

Our society is facing a public health challenge due to the increasing presence of Endocrine Disrupting Chemicals (EDCs) in the environment. Developmental exposure to EDCs, by interacting with endogenous hormonal pathways, disrupts the organization of the central nervous system leading to life long-lasting consequences. Exposure during such critical period of development may interfere with germ cell development, affecting th next generations.Our goal was (1) to study the effects of developmental or adult exposure to low doses of BPA on the neuroendocrine control of reproduction in females; and (2) to study the effects of exposure to a low dose EDC mixture on sexual maturation and maternal care across generations. We have shown that adult BPA exposure transiently disrupts estrous cyclicity and ovarian follicle development by affecting the preovulatory LH surge. Perinatal exposure to EDC mixture transgenerationally alters sexual maturation and reproductive function throughout epigenetic reprogramming of the neural network controlling GnRH secretion. Such exposure also induces a multigenerational loss of dopamine signaling and maternal care. A cross-fostering paradigm indicated a potential germline transmission explaining the transgenerational reproductive phenotype.Overall, we identified alterations of the hypothalamic control of reproduction and maternal behavior in female rats up to the fourth generation after EDC exposure. These results raise concerns about the legacy we give to future generations and urge to further evaluate the effects of EDCs across generations in human populations.