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妊娠暴露于全氟壬酸对新生小鼠睾丸的影响。

Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes.

机构信息

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

出版信息

J Appl Toxicol. 2019 Dec;39(12):1663-1671. doi: 10.1002/jat.3883. Epub 2019 Aug 6.

Abstract

Perfluoroalkyl acids (PFAAs) are widely used in commercial products and are found in many goods of daily use. Perfluorononanoic acid (PFNA) is one of the PFAAs that possesses endocrine disrupting properties and we have recently shown that PFNA affects testicular functions in Parkes mice. Exposure to environmental endocrine disruptors during fetal life is believed to affect gonadal development and they might produce reproductive abnormalities in males. Therefore, the present study examined the effect of gestational exposure to PFNA on the testes of neonatal mice offspring. Pregnant Parkes mice were orally administered PFNA (2 and 5 mg/kg body weight) or distilled water from gestational day 12 until parturition. Male pups were killed on postnatal day 3. PFNA treatment decreased testosterone biosynthesis by inhibiting expression of steroidogenic acute regulatory protein, cytochrome P450scc, and 3β- and 17β-hydroxysteroid dehydrogenase; proliferation of testicular cells was also affected in treated mice. Furthermore, a marked decrease in expression of Wilms tumor 1, steroidogenic factor 1 and insulin-like factor 3 was noted in neonatal mice testes, indicating that the PFNA treatment may affect the development of the testis. Moreover, observation of the dose-related expression of anti-müllerian hormone and c-Kit in neonatal mice testes is also suggestive of an interference with gonadal development by PFNA exposure. In conclusion, the results suggest that the gestational exposure to PFNA decreased testosterone biosynthesis and altered the expression of critical factors involved in the development of the testis, thereby advocating a potential risk of PFNA to male reproductive health.

摘要

全氟烷基酸(PFAAs)广泛应用于商业产品中,存在于许多日常用品中。全氟壬酸(PFNA)是具有内分泌干扰特性的 PFAAs 之一,我们最近表明,PFNA 会影响 Parkes 小鼠的睾丸功能。人们认为,胎儿期暴露于环境内分泌干扰物会影响性腺发育,并可能导致雄性产生生殖异常。因此,本研究探讨了妊娠期暴露于 PFNA 对新生小鼠睾丸的影响。从妊娠第 12 天到分娩,给妊娠 Parkes 小鼠口服 PFNA(2 和 5mg/kg 体重)或蒸馏水。雄性幼鼠在出生后第 3 天处死。PFNA 通过抑制类固醇生成急性调节蛋白、细胞色素 P450scc 和 3β-和 17β-羟甾脱氢酶的表达,减少了睾丸酮的生物合成;处理小鼠的睾丸细胞增殖也受到影响。此外,在新生小鼠睾丸中还观察到 Wilms 肿瘤 1、类固醇生成因子 1 和胰岛素样因子 3 的表达明显下降,表明 PFNA 处理可能影响睾丸的发育。此外,对新生小鼠睾丸中抗 Müllerian 激素和 c-Kit 的剂量相关表达的观察也表明,PFNA 暴露可能干扰性腺发育。总之,这些结果表明,妊娠期暴露于 PFNA 会降低睾丸酮的生物合成,并改变参与睾丸发育的关键因子的表达,从而表明 PFNA 对男性生殖健康存在潜在风险。

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