Bisphenol A induces sex-dependent alterations in the neuroendocrine response of Djungarian hamsters to photoperiod

In nature, species synchronize reproduction and energy metabolism with seasons to optimize survival and growth. This study investigates the effect of oral exposure to bisphenol A (BPA) on phenotypic and neuroendocrine seasonal adaptations in the Djungarian hamster, which in contrast to conventional laboratory rodents, is a well-recognized seasonal model. Adult female and male hamsters were orally exposed to BPA (5, 50, or 500 μg/kg/d) or vehicle during a 10-week transition from a long (LP) to short (SP) photoperiod (winter transition) or vice versa (summer transition). Changes in body weight, food intake, and pelage color were monitored weekly and, at the end of the exposure, expression of hypophysio-hypothalamic markers of photoperiodic (TSHβ, deiodinases), reproductive (Rfrp, kisspeptin) and metabolic (somatostatin, Pomc) integration, reproductive organ activity, and glycemia were assessed. Our results revealed sex-specific effects of BPA on acquiring SP and LP phenotypes. During LP to SP transition, females exposed to 500 μg/kg/d BPA exhibited delayed body weight loss and reduced feed efficiency associated with a lower expression of somatostatin, while males exposed to 5 μg/kg/d BPA showed an accelerated acquisition of SP-induced metabolic parameters. During SP to LP transition, females exposed to 5 μg/kg/d BPA displayed a faster LP adaptation in reproductive and metabolic parameters, along with kisspeptin downregulation occurring 5 weeks earlier and Pomc upregulation delayed for up to 10 weeks. In males, BPA exposure led to decreased expression of central photoperiodic integrators, with no effect on the acquisition of the LP phenotype. This pioneering study investigating EDCs' effects on mammalian seasonal physiology shows that BPA alters the dynamics of metabolic adaptation to both SP and LP transitions with marked sex dimorphism, causing temporal discordance in seasonal adaptation between males and females. These findings emphasize the importance of investigating EDCs' effects on non-conventional animal models, providing insights into wildlife physiology.