Epigenetic dysregulation of Mdr1b in the blood-testis barrier contributes to dyszoospermia in mice exposed to cadmium
Epigenetic dysregulation of Mdr1b in the blood-testis barrier contributes to dyszoospermia in mice exposed to cadmium
复制标题
血睾屏障中 Mdr1b 的表观遗传失调导致暴露于镉的小鼠精子不良
DOI：
10.1016/j.ecoenv.2019.110142
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发表时间：
2020-03-01
影响因子：
6.8
通讯作者：
Zhong, Shan
中科院分区：
文献类型：
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作者：
Fang, Yu;Xiang, Ying;Zhong, Shan
据报道，镉(Cd)可引起生殖毒性。最近的研究表明，多药耐药基因1b(MDR1b)的表观遗传异常调节导致异种异体外排障碍(BTB)。然而，MDR1b调节失调是否参与了CD介导的精子症及其潜在的机制仍不清楚。在这项研究中，小鼠每隔一天灌胃给予0或2.5 mg/kg的氯化镉，连续2个月，以研究精子发生和mdr1b的表观遗传调节的变化。培养小鼠间质细胞TM3，检测MDR1b的表达定位。我们发现，Cd组出现了BTB断裂，并伴有明显的精子畸形和动态损伤。MDR1b启动子高甲基化和核因子Ya(Nfya)募集减少与Cd引起的精子活力低下有关。总之，这些发现提供了体内证据，表明BTB中mdr1b的表观遗传失调是镉暴露引起精子障碍的潜在原因。
Cadmium (Cd) has been reported to induce reproductive toxicity. Recent study indicated that aberrant epigenetic regulation of Multidrug resistance 1b (Mdr1b) causes xenobiotic efflux failure at the blood-testis barrier (BTB). However, whether Mdr1b dysregulation is involved in Cd-mediated dyszoospermia and the underlying mechanism remain unknown. In this study, mice were intragastrically administered 0 or 2.5 mg/kg CdCl2 every other day for 2 months to investigate changes in spermatogenesis and epigenetic regulation of Mdr1b. Mouse Leydig cells TM3 were cultured to detect Mdr1b expression localization. We found that the Cd group revealed BTB disruption concomitant with obvious sperm abnormity and dynamic impairment. Hypermethylation and decreased nuclear factor Ya (Nfya) recruitment to the Mdr1b promoter were correlated with low sperm motility in response to Cd. In conclusion, these findings provide in vivo evidence that epigenetic dysregulation of Mdr1b in the BTB is a potential cause of dyszoospermia upon Cd exposure.