Perinatal exposure to bisphenol A or S alters differently sexual behavior and kisspeptin system in mice

Abstract

The effects of bisphenol A (BPA), a highly diffused endocrine-disrupting chemical found mainly in plastics, on neural circuits and behaviors are well-known. However, the effects of its substitutes have not been fully investigated. Thus, in the present study, we compare the effects of perinatal exposure to bisphenol A or S (BPS) on reproductive behaviors and related hypothalamic kisspeptin system in mice. C57BL/6J dams were orally treated with 4 μg/kg body weight/day of BPA, BPS, or vehicle from mating until the weaning of the offspring. In the adult offspring, we performed the two-bedding T-Maze test, and we observed the spontaneous sexual behavior. Exposure to BPA caused a delay in puberty onset in females, while BPS caused anticipation in males, and both altered the estrous cycle in females. The sexual and sexual-related behaviors were partially altered in males, especially in the BPA-exposed ones. Regarding the kisspeptin immunoreactivity in the analyzed hypothalamic nuclei, in BPA- or BPS-treated females, we observed an increase within the rostral periventricular area, while BPA led to an increase in the paraventricular nucleus, and BPS induced a reduction compared to control females. Among males, we observed a significant increase in the arcuate nucleus of BPA-treated males and a significant decrease in the paraventricular nucleus of BPS-treated ones. These results support the idea that perinatal exposure to low doses of either BPA or BPS is altering, in a sexually differentiated way, some reproductive-relevant parameters, sexual behaviors, and kisspeptin hypothalamic nuclei.

Keywords: Arcuate nucleus; Endocrine disrupting chemicals; Hypothalamus; Paraventricular nucleus; Rostral periventricular area of the third ventricle.