Developmental exposure to Ethinylestradiol affects transgenerationally sexual behavior and neuroendocrine networks in male mice

Reproductive behavior and physiology in adulthood are controlled by hypothalamic sexually dimorphic neuronal networks which are organized under hormonal control during development. These organizing effects may be disturbed by endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to Ethinylestradiol (EE2) may alter reproductive parameters in adult male mice and their progeny, Swiss mice (F1 generation) were exposed from prenatal to peripubertal periods to EE2 (0.1–1 μg/kg/d). Sexual behavior and reproductive physiology were evaluated on F1 males and their F2, F3 and F4 progeny. EE2-exposed F1 males and their F2 to F4 progeny exhibited EE2 dose-dependent increased sexual behavior, with reduced latencies of first mount and intromission, and higher frequencies of intromissions with a receptive female. The EE2 1 μg/kg/d exposed animals and their progeny had more calbindin immunoreactive cells in the medial preoptic area, known to be involved in the control of male sexual behavior in rodents. Despite neuroanatomical modifications in the Gonadotropin-Releasing Hormone neuron population of F1 males exposed to both doses of EE2, no major deleterious effects on reproductive physiology were detected. Therefore EE2 exposure during development may induce a hypermasculinization of the brain, illustrating how widespread exposure of animals and humans to EDCs can impact health and behaviors.