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Effects of In Utero Exposure to Di-n-Butyl Phthalate on Testicular Development in Rat

机译:子宫内邻苯二甲酸二丁酯对大鼠睾丸发育的影响

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摘要

Humans are inevitably exposed to ubiquitous phthalate esters (PAEs). In utero exposure to di-n-butyl phthalate (DBP) induces abnormal development of the testis and reproductive tract in male offspring, which correspond closely with the human condition of testicular dysgenesis syndrome (TDS)-like syndrome. However, the underlying mechanisms have not been elucidated in detail. In this study, pregnant rats were orally exposed to either corn oil (controls) or DBP at three different doses by gavage during Gestational Days 12.5–21.5. Pathological examinations were performed for toxicity evaluation. Proliferation and apoptosis related proteins (ras related dexamethasone induced 1 (Rasd1), mitogen-activated protein kinase kinases1/2 (MEK1/2), Bcl-2, and Bax) were measured for mechanisms exploration. The results showed that different doses of DBP caused male developmental and reproductive toxicity in rats, including the decrease of anogenital distance (AGD), the histological damage of testis, and apoptosis of seminiferous tubule cells. Our data suggested that DBP played chronic and continuous toxic roles on male reproductive system by disrupting expression of Rasd1 and MEK1/2 as well as Bcl-2/Bax ratio. Further research is warranted.
机译:人体不可避免地会接触到普遍存在的邻苯二甲酸酯(PAE)。在子宫内暴露于邻苯二甲酸二正丁酯(DBP)会诱发雄性后代睾丸和生殖道的异常发育,这与人类睾丸发育不全综合征(TDS)状综合征的人类状况密切相关。但是,尚未详细阐明其基本机制。在这项研究中,妊娠期12.5至21.5天,通过管饲法以三种不同剂量给怀孕大鼠口服玉米油(对照)或DBP。进行病理检查以评估毒性。测量与增殖和凋亡相关的蛋白质(ras相关的地塞米松诱导1(Rasd1),促分裂原激活的蛋白激酶激酶1/2(MEK1 / 2),Bcl-2和Bax),以探索机制。结果表明,不同剂量的DBP引起大鼠雄性发育和生殖毒性,包括肛门生殖器距离的减少,睾丸的组织学损伤和生精小管细胞的凋亡。我们的数据表明,DBP通过破坏Rasd1和MEK1 / 2的表达以及Bcl-2 / Bax的比例,对男性生殖系统起慢性和持续毒性作用。值得进一步研究。

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