Bonaldo Brigitta, Casile Antonino, Bettarelli Martina, Marraudino Marilena, Gotti Stefano
Department of Health Sciences and Research Center on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale (UPO), Novara, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole, 10-10043, Orbassano, Turin, Italy.
Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole, 10-10043, Orbassano, Turin, Italy; School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 9, Camerino, 62032, Italy.
Environ Res. 2025 Mar 15;269:120888. doi: 10.1016/j.envres.2025.120888. Epub 2025 Jan 18.
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.
双酚A（BPA）是一种主要存在于塑料中的高度扩散的内分泌干扰化学物质，其对神经回路和行为的影响已为人所知。然而，其替代品的影响尚未得到充分研究。因此，在本研究中，我们比较了围产期暴露于双酚A或双酚S（BPS）对小鼠生殖行为和相关下丘脑吻素系统的影响。将C57BL/6J母鼠从交配至后代断奶期间，每天经口给予4μg/kg体重的双酚A、双酚S或赋形剂。在成年后代中，我们进行了双垫料T迷宫试验，并观察了自发性行为。暴露于双酚A会导致雌性青春期开始延迟，而双酚S会导致雄性青春期提前，并且两者都会改变雌性的发情周期。雄性的性行为和与性相关的行为部分发生改变，尤其是暴露于双酚A的雄性。关于所分析的下丘脑核中的吻素免疫反应性，在双酚A或双酚S处理的雌性中，我们观察到吻素免疫反应性在室周前部区域增加，而双酚A导致室旁核增加，与对照雌性相比，双酚S诱导减少。在雄性中，我们观察到双酚A处理的雄性弓状核显著增加，双酚S处理的雄性室旁核显著减少。这些结果支持这样一种观点，即围产期暴露于低剂量的双酚A或双酚S会以性别分化的方式改变一些与生殖相关的参数、性行为和下丘脑吻素核。
