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母体哺乳期暴露于 BDE-209 会抑制睾丸类固醇生成,并损害青春期前小鼠后代的支持细胞分化,从而抑制生殖细胞增殖。

Inhibition of testicular steroidogenesis and impaired differentiation of Sertoli cells in peripubertal mice offspring following maternal exposure to BDE-209 during lactation suppress germ cell proliferation.

机构信息

Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.

Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.

出版信息

Toxicol Lett. 2018 Jun 15;290:83-96. doi: 10.1016/j.toxlet.2018.03.026. Epub 2018 Mar 22.

DOI:10.1016/j.toxlet.2018.03.026
PMID:29578053
Abstract

Polybrominated diphenyl ethers (PBDEs) are used for fire prevention purpose. BDE-209, a congener of PBDEs, is thyroid hormones (THs)-disrupting chemical because of its structural similarity with THs. Testis is considered as THs-responsive organ and is more susceptible to chemical agents during peripubertal period. This study, therefore, evaluated the effect and possible mechanism(s) of action of maternal exposure to BDE-209 during lactation on germ cell proliferation, testicular steroidogenesis and on differentiation of Sertoli cells (SCs) in relation to altered THs status in peripubertal mice offspring. Lactating Parkes mice were gavaged with 500 and 700 mg/kg BW of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28 along with 6-propyl-2-thiouracil (PTU)-treated positive controls and vehicle-treated controls. Male pups of lactating dams were sacrificed at PND 42. Maternal exposure to BDE-209 during lactation markedly affected testicular histopathology, germ cell proliferation and steroidogenesis with down-regulated expression of various steroidogenic markers in peripubertal mice offspring. Decreased expressions of maturational markers of SCs with a decline in serum THs levels were also evident in these offspring. Results thus suggest that maternal BDE-209 exposure during lactation impairs germ cell proliferation via inhibition of steroidogenic pathway and differentiation of SCs in peripubertal mice offspring.

摘要

多溴联苯醚(PBDEs)被用于防火目的。BDE-209 是 PBDEs 的一种同系物,由于其与甲状腺激素(THs)的结构相似,是一种甲状腺激素干扰化学物质。睾丸被认为是 THs 反应性器官,并且在青春期前期间更容易受到化学物质的影响。因此,本研究评估了哺乳期母体暴露于 BDE-209 对生殖细胞增殖、睾丸类固醇生成以及与青春期前小鼠后代 THs 状态改变相关的支持细胞(SCs)分化的影响及其可能的作用机制。哺乳期 Parkes 小鼠从产后第 1 天(PND)1 至 PND 28 每天用玉米油灌胃 500 和 700mg/kg BW 的 BDE-209,同时用 6-丙基-2-硫代尿嘧啶(PTU)处理阳性对照和溶剂对照。哺乳期母鼠的雄性幼仔在 PND 42 时被处死。哺乳期母体暴露于 BDE-209 明显影响睾丸组织病理学、生殖细胞增殖和类固醇生成,导致青春期前小鼠后代各种类固醇生成标志物的表达下调。这些后代的 SCs 成熟标志物表达减少,血清 THs 水平下降。结果表明,哺乳期母体 BDE-209 暴露通过抑制类固醇生成途径和青春期前小鼠后代 SCs 的分化来损害生殖细胞增殖。

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