A commercial Roundup® formulation induced male germ cell apoptosis by promoting the expression of XAF1 in adult mice
A commercial Roundup® formulation induced male germ cell apoptosis by promoting the expression of XAF1 in adult mice
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商业农达®配方通过促进成年小鼠 XAF1 的表达诱导雄性生殖细胞凋亡
DOI：
10.1016/j.toxlet.2018.06.1067
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发表时间：
2018-10-15
影响因子：
3.5
通讯作者：
Liu, Jin-yi
中科院分区：
文献类型：
--
作者：
Jiang, Xiao;Zhang, Ning;Liu, Jin-yi
综述（R）广泛用于全球杂草控制。该化合物的残留物可能导致雄性生殖系统的副作用。但是，雄性生殖细胞的综述（R）的毒性作用和机制尚不清楚。我们的目的是研究综述（R）对小鼠男性生殖细胞的凋亡诱导作用，并探讨在此过程中涉及的新型肿瘤抑制XAF1（与凋亡相关因子1）的作用。我们证明了综述（R）会损害精子发生，降低精子运动和浓度，并增加小鼠的精子畸形率。此外，在体外和体内暴露（r）暴露后，生殖细胞过多的生殖细胞凋亡伴随着XAF1的过表达。此外，由综述（R）诱导的XIAP（X连锁抑制剂）的低表达与XAF1成反比。此外，在综述（R）暴露后，XAF1的敲低减弱了生殖细胞凋亡，改善了XIAP表达并抑制其下游靶蛋白Caspase-3和PARP的激活。综上所述，我们的数据表明XAF1在综述（R）诱导的男性生殖细胞凋亡中起重要作用。本研究表明，综述（R）暴露对哺乳动物的男性生殖健康具有潜在的负面影响。
Roundup (R) is extensively used for weed control worldwide. Residues of this compound may lead to side effects of the male reproductive system. However, the toxic effects and mechanisms of Roundup (R) of male germ cells remain unclear. We aimed to investigate the apoptosis-inducing effects of Roundup (R) on mouse male germ cells and explore the role of a novel tumor suppressor XAF1 (X-linked inhibitor of apoptosis-associated factor 1) involved in this process. We demonstrated that Roundup (R) can impair spermatogenesis, decrease sperm motility and concentration, and increase the sperm deformity rate in mice. In addition, excessive apoptosis of germ cells accompanied by the overexpression of XAF1 occurred after Roundup (R) exposure both in vitro and in vivo. Furthermore, the low expression of XIAP (X-linked inhibitor of apoptosis) induced by Roundup (R) was inversely correlated with XAF1. Moreover, the knockdown of XAF1 attenuated germ cell apoptosis, improved XIAP expression and inhibited the activation of its downstream target proteins, caspase-3 and PARP, after Roundup (R) exposure. Taken together, our data indicated that XAF1 plays an important role in Roundup (R)-induced male germ cell apoptosis. The present study suggested that Roundup (R) exposure has potential negative implications on male reproductive health in mammals.