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首页> 外文期刊>Environmental Science & Technology >Maternal Exposure to Di-n-butyl Phthalate Promotes the Formation of Testicular Tight Junctions through Downregulation of NF-κB/ COX-2/PGE_2/MMP-2 in Mouse Offspring
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Maternal Exposure to Di-n-butyl Phthalate Promotes the Formation of Testicular Tight Junctions through Downregulation of NF-κB/ COX-2/PGE_2/MMP-2 in Mouse Offspring

机译：邻苯二甲酸二叔丁酯的母体暴露促进睾丸紧密连接的形成通过小鼠后代NF-κB/ COX-2 / PGE_2 / MMP-2的下调

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摘要

Previous studies demonstrated that maternal exposure to di-n-butyl phthalate (DBP) resulted in developmental disorder of the male reproductive organ; however, the underlying mechanism has not been thoroughly elucidated to date. The present study was aimed to investigate the effects of maternal exposure to DBP on the formation of the Sertoli cell (SC)-based tight junctions (TJs) in the testes of male offspring mice and the underlying molecular mechanism. By observing the pathological structure and ultrastructure, permeability analysis of the testis of 22 day male offspring in vivo, and transepithelial electrical resistance measurement of inter-SCs in vitro, we found that the formation of TJs between SCs in offspring mice was accelerated, which was paralleled by the accumulation of TJ protein occludin at 50 mg/kg/day DBP exposure in utero and 0.1 mM monobutyl phthalate (MBP, the active metabolite of DBP) in vitro. Our in vitro results demonstrated that 0.1 mM MBP downregulated the expression of matrix metalloproteinase-2 (MMP-2) by inhibiting the activation of nuclear factor-κB (NF-κB)/cyclooxygenase-2 (COX-2)/ prostaglandin E2 (PGE_2) cascades via attenuated binding of NF-κB to both the MMP-2 promoter and COX-2 promoter. Taken together, the data confirmed that maternal exposure to a relatively low dose of DBP promoted the formation of testicular TJs through downregulation of NF-κB/COX-2/PGE_2/MMP-2, which might promote the development of the testis during puberty. Our findings may provide new perspectives for prenatal DBP exposure, which is a potential environmental contributor, leading to earlier puberty in male offspring mice.
机译：以前的研究表明，母体暴露于邻苯二甲酸二丁酯（DBP）导致雄性生殖器官的发育障碍;然而，迄今尚未彻底阐明潜在机制。本研究旨在探讨母体暴露对DBP的影响，在雄性后代小鼠和潜在的分子机制中形成血液细胞（SC）的紧密结合（TJ）。通过观察病理结构和超微结构，睾丸22天的术术中的睾丸分析，以及体外静脉间的Transepeallial电阻测量，我们发现，加速了后代小鼠SCS之间的TJS形成，即通过在UTERO和0.1mM单丁酯（MBP，DBP的活性代谢物）中的50mg / kg /天的DBP暴露于50mg / kg /天的DBP暴露于50mg / kg /天的DBP暴露。我们的体外结果表明，0.1mm MBP通过抑制核因子-κB（NF-κB）/环氧氧酶-2（COX-2）/前列腺素E2（PGE_2）的激活来下调基质金属蛋白酶-2（MMP-2）的表达）通过衰减NF-κB的级联级联，对MMP-2启动子和COX-2启动子进行衰减结合。在一起，数据确认，通过NF-κB/ COX-2 / PGE_2 / MMP-2的下调，母体暴露于相对低剂量的DBP促进了睾丸TJ的形成，这可能在青春期期间促进睾丸的发展。我们的调查结果可能为产前DBP曝光提供新的视角，这是一个潜在的环境贡献者，导致男性后代小鼠早期的青春期。

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  • 来源
    《Environmental Science & Technology》 |2020年第13期|8245-8258|共14页
  • 作者

    Tan Ma; Yuan Zhou; Yunhui Xia; Xiannan Meng; Haibo Jin; Bo Wang; Yusheng Chen; Jiayin Qiu; Jiang Wu; Jie Ding; Xiaodong Han; Dongmei Li;

  • 作者单位

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratoty of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

    Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School and Jiangsu Key Laboratory of Molecular Medicine Nanjing University Nanjing Jiangsu 210093 China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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