Adolescent exposure to bisphenol-a antagonizes androgen regulation of social behavior in male mice

IF 2.6 3区 医学 Q3 NEUROSCIENCES Neurotoxicology and teratology Pub Date : 2024-08-02 DOI:10.1016/j.ntt.2024.107374
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Abstract

Social behavior is sexually dimorphic, which is regulated by gonadal hormones in the brain. Our recent study found that exposure to low doses of bisphenol-A (BPA) during adolescence, permanently alters social behavior in adult male mice, but the underlying mechanisms remain unclear. Using adolescent gonadectomy (GDX) male mice with testosterone propionate (TP, 0.5 mg/kg) supplement (TP-GDX), this study showed that BPA antagonized promoting effects of TP on social interaction, sexual behavior, and aggression in GDX mice. BPA eliminated the reversal effects of TP on GDX-induced decrease in the number of immunoreactive to arginine vasopressin (AVP-ir) neurons in the medial amygdala (MeA) and the levels of AVP receptor 1a (V1aR) in the MeA and the nucleus accumbens (NAc). In addition, BPA removed down-regulation in the levels of dopamine (DA) transporter (DAT) and DA receptor 1 (DR1) in the NAc of TP-GDX mice. BPA exposure reduced testosterone (T) levels in the brain and serum and the expression of androgen receptor (AR) protein in the amygdala and striatum of sham-operated and TP-GDX males. These results suggest that adolescent exposure to BPA inhibits regulation of androgen in AVP and DA systems of the brain regions associated with social behavior, and thus alters social behaviors of adult male mice.

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雄性小鼠在青春期接触双酚 A 会拮抗雄性激素对其社会行为的调节。
社交行为具有性别二态性,受大脑中性腺激素的调节。我们最近的研究发现,在青春期暴露于低剂量的双酚 A(BPA)会永久性地改变成年雄性小鼠的社会行为,但其潜在机制仍不清楚。本研究使用青春期性腺切除(GDX)雄性小鼠,并辅以丙酸睾酮(TP,0.5 mg/kg)(TP-GDX),结果表明双酚 A 可拮抗 TP 对 GDX 小鼠社会交往、性行为和攻击行为的促进作用。双酚 A 可消除 TP 对 GDX 引起的内侧杏仁核(MeA)精氨酸血管加压素(AVP-ir)免疫反应神经元数量减少以及 MeA 和纳氏核(NAc)中 AVP 受体 1a (V1aR)水平下降的逆转效应。此外,双酚 A 还消除了 TP-GDX 小鼠 NAc 中多巴胺(DA)转运体(DAT)和 DA 受体 1(DR1)水平的下调。暴露于双酚 A 会降低假手术和 TP-GDX 雄性小鼠大脑和血清中的睾酮(T)水平,以及杏仁核和纹状体中雄激素受体(AR)蛋白的表达。这些结果表明,青春期暴露于双酚 A 会抑制与社会行为相关的脑区 AVP 和 DA 系统对雄性激素的调节,从而改变成年雄性小鼠的社会行为。
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来源期刊
CiteScore
5.60
自引率
10.30%
发文量
48
审稿时长
58 days
期刊介绍: Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.
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