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环境相关的 DEHP 在妊娠期和哺乳期暴露会抑制细丝蛋白 A 在睾丸中的表达。

Environmentally relevant DEHP exposure during gestational and lactational period inhibits filamin a testicular expression.

机构信息

Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Científicas y Técnicas, Córdoba, Argentina.

Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

出版信息

J Mol Histol. 2023 Oct;54(5):509-520. doi: 10.1007/s10735-023-10144-7. Epub 2023 Aug 12.

Abstract

Toxicological studies have revealed that DEHP exposure during pregnancy may induce developmental disorders, especially in male offspring, leading to morphological and functional alterations in the reproductive system by mechanisms that should be investigated. Thus, the aim of this work was to analyze the testicular toxicity induced by an environmentally relevant DEHP dose during development and its impact on FLNA, a protein that participates in the blood-testis barrier assembly. We used male Wistar rats exposed to DEHP during pregnancy and lactation. The results showed that DEHP exposure during development and lactation increased body weight, decreased gonadal weight and shortened anogenital distance. This phthalate induced morphological changes in the testis, suggestive of hypospermatogenesis. DEHP exposure decreased the number of FLNA positive cells and the expression of FLNA and claudin-1 in prepubertal testes. Furthermore, DEHP inhibited FLNA and claudin-1 protein expression in adult male rats. These results indicated that exposure to DEHP during gestation and lactation perturbed testis development and suggested that FLNA is a target protein of DEHP, possibly contributing to the phthalate-induced damage on BTB.

摘要

毒理学研究表明,怀孕期间 DEHP 暴露可能会导致发育障碍,特别是在雄性后代中,通过需要研究的机制导致生殖系统的形态和功能改变。因此,本工作的目的是分析在发育过程中环境相关 DEHP 剂量引起的睾丸毒性及其对 FLNA 的影响,FLNA 是一种参与血睾屏障组装的蛋白质。我们使用雄性 Wistar 大鼠进行了 DEHP 暴露的实验,实验涉及妊娠和哺乳期。结果表明,在发育和哺乳期暴露于 DEHP 会增加体重,降低性腺重量并缩短肛殖距离。这种邻苯二甲酸酯会导致睾丸形态发生变化,提示精子生成减少。DEHP 暴露会减少 FLNA 阳性细胞的数量,并降低青春期前睾丸中 FLNA 和 Claudin-1 的表达。此外,DEHP 抑制了成年雄性大鼠中 FLNA 和 Claudin-1 蛋白的表达。这些结果表明,妊娠和哺乳期暴露于 DEHP 会干扰睾丸发育,并表明 FLNA 是 DEHP 的靶蛋白,可能导致 BTB 上的邻苯二甲酸酯损伤。

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