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围产期暴露于双酚A或双酚S会不同程度地改变小鼠的性行为和促性腺激素释放激素神经元激活蛋白系统。

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

作者信息

Bonaldo Brigitta, Casile Antonino, Bettarelli Martina, Marraudino Marilena, Gotti Stefano

机构信息

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.

出版信息

Environ Res. 2025 Mar 15;269:120888. doi: 10.1016/j.envres.2025.120888. Epub 2025 Jan 18.

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.

摘要

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。

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