PM2.5 exposure impairs sperm quality through testicular damage dependent on NALP3 inflammasome and miR-183/96/182 cluster targeting FOXO1 in mouse
PM2.5 exposure impairs sperm quality through testicular damage dependent on NALP3 inflammasome and miR-183/96/182 cluster targeting FOXO1 in mouse
复制标题
PM2.5 暴露通过依赖于小鼠中 NALP3 炎性体和靶向 FOXO1 的 miR-183/96/182 簇的睾丸损伤损害精子质量
DOI：
10.1016/j.ecoenv.2018.10.108
复制
发表时间：
2019-03-01
影响因子：
6.8
通讯作者：
Zhang, Rong
中科院分区：
文献类型：
--
作者：
Zhou, Lixiao;Su, Xuan;Zhang, Rong
暴露于环境细颗粒物（PM2.5）已明确与男性生殖障碍。然而，进行了非常有限的毒理学研究来研究PM2.5诱导精子质量下降的潜在机制。本研究通过建立真实的时间PM2.5全身暴露小鼠模型，探讨PM2.5对小鼠精子质量的影响及其可能机制。将60只雄性C57 BL/6小鼠随机分为3组：过滤空气组、未过滤空气组和浓缩空气组。当暴露持续时间累积至8周时，每组中一半小鼠被处死用于研究，其余小鼠在暴露16周时被处死。我们的研究结果表明，PM2.5暴露可导致循环白色血细胞和肺部炎症显着增加。PM2.5暴露可引起睾丸DNA损伤和组织病理学改变。PM2.5暴露16周后，小鼠精子密度显著降低，睾丸组织睾酮水平下降。PM2.5暴露后，精子活动率降低，形态异常精子增多，并呈时间和剂量依赖性。PM2.5暴露显著增加了睾丸中NACHT、LRR和PYD结构域蛋白3（NALP 3）炎性体主要组分的表达，伴随着靶向FOX 01的miR-183/96/182的表达增加。目前的数据表明，PM2.5引起的精子质量下降可以部分解释为睾丸中的炎症反应，这可能是全身炎症的结果。其分子机制是通过激活NALP 3炎性体并结合靶向FOXO 1的miR-183/96/182来实现的。
Exposure to ambient fine particular matter (PM2.5) has been clearly associated with male reproductive disorders. However, very limited toxicological studies were carried out to investigate the potential mechanisms underlying the PM2.5-induced sperm quality decline. In the present study, we established a real time whole body PM2.5 exposure mouse model to investigate the effects of PM2.5 on sperm quality and its potential mechanisms. Sixty male C57BL/6 mice were randomly subjected to three groups: filtered air group, unfiltered air group and concentrated air group. Half of the mice from each group were sacrificed for study when the exposure duration accumulated to 8 weeks and the rest of the mice were sacrificed when exposed for 16 weeks. Our results suggested that PM2.5 exposure could induce significant increases in circulating white blood cells and inflammation in lungs. PM2.5 exposure induced apparently DNA damages and histopathologic changes in testes. There were significantly decreased sperm densities of mice, which were paralleled with the down-regulated testosterone levels in testes tissue of mice after exposure to PM2.5 for 16 weeks. The numbers of motile sperms were decreased and sperms with abnormal morphology were increased after PM2.5 exposure in a time-depended and dose-depended manner. PM2.5 exposure significantly increased the expression of the major components of the NACHT, LRR and PYD domains-containing protein3 (NALP3) inflammasome, accompanied by the increased expression of miR-183/96/182 targeting FOX01 in testes. The present data demonstrated that sperm quality decline induced by PM2.5 could be partly explained by the inflammatory reaction in testes which might be a consequence of systemic inflammation. The molecular mechanism was depended on the activation of NALP3 inflammasome accompanied by miR-183/96/182 targeting FOXO1 in testes.