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Exposure of human fetal penile cells to different PCB mixtures: transcriptome analysis points to diverse modes of interference on external genitalia programming.

机译:人类胎儿的阴茎细胞暴露于不同的PCB混合物中:转录组分析表明对外部生殖器编程的多种干扰方式。

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摘要

The effects exerted by three mixtures of Polychlorinated Biphenyls (PCBs) were evaluated on human fetal corpora cavernosa cells, as a model for male external genitalia development. The three mixtures feature congeners grouped according to potentially shared modes of action: one dioxin-like (DL) (Mix2) and two non dioxin-like (NDL) mixtures featuring congeners defined as estrogenic (Mix1) and highly persistent-cytochrome P-450 inducers (Mix3). Congeners concentrations used were derived from human internal exposure data. Toxicogenomic analysis revealed that all mixtures modulated critical genes involved in genitourinary development, however displaying three different expression profiles. The DL Mix2 modulated actin-related, cell-cell and epithelial-mesenchymal communication morphogenetic processes; Mix1 modulated smooth muscle function genes, whereas Mix3 mainly modulated genes involved in cell metabolism (e.g., steroid and lipid synthesis) and growth. Our data indicate that fetal exposure to environmentally relevant PCB levels modulates several patterns of genitourinary programming; moreover, NDL congener groups may have specific modes of action.
机译:作为人类外部生殖器发育的模型,评估了三种多氯联苯混合物(PCBs)对人胎儿海绵体细胞的作用。三种混合物的同源物根据可能共享的作用方式进行分组:一种二恶英样(DL)(Mix2)和两种非二恶英样(NDL)混合物,其特征为同源的定义为雌激素(Mix1)和高度持久的细胞色素P-450诱导剂(Mix3)。使用的同类物浓度来自人类内部暴露数据。毒理基因组学分析显示,所有混合物均调节了涉及泌尿生殖系统发育的关键基因,但显示出三种不同的表达谱。 DL Mix2调节肌动蛋白相关的,细胞间和上皮-间质通讯的形态发生过程; Mix1调节平滑肌功能基因,而Mix3主要调节参与细胞代谢(例如,类固醇和脂质合成)和生长的基因。我们的数据表明,胎儿暴露于与环境有关的多氯联苯水平可调节泌尿生殖系统编程的几种模式。此外,NDL同族群可能具有特定的作用方式。

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