Ge Pan, Wang Si-Yu, Zhang Xiang, Yang Yan-Qi, Lv Mo-Qi, Sun Ying, Zhang Jian, Wang Xiao-Ting, Liu Ming, Zhou Dang-Xia
Department of Pathology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Department of Gynecology and Obstetrics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710001, China.
Reprod Sci. 2025 Sep 5. doi: 10.1007/s43032-025-01965-w.
As space exploration advances, the effects of the microgravity environment on testicular injury and spermatogenic function in astronauts have attracted widespread attention, but the underlying mechanisms remain unclear.
In this study, testicular morphometry and Johnsen score were used to evaluate the degree of testicular injury. Then the upstream transcription factors of MeCP2 were verified using the dual-luciferase reporter assay. Finally, the expression of C/EBP-β, MeCP2, and Wnt4/β-Catenin protein was detected to clarify the regulatory pathway.
Under microgravity conditions, MeCP2 expression was significantly reduced in rat testes and was positively correlated with testicular morphometric indices. Subsequently, the dual-luciferase reporter assay revealed that C/EBP-β directly bound to the promoter sequence of MeCP2, initiating its transcriptional activity. Meanwhile, the expression of C/EBP-β, Wnt4, and β-Catenin was reduced in the testes under microgravity conditions.
In conclusion, our study proposed that C/EBP-β regulated MeCP2, consequently, inhibited the Wnt4/β-Catenin pathway activity, thereby participating in microgravity-induced testicular injury.
随着太空探索的推进,微重力环境对宇航员睾丸损伤及生精功能的影响已引起广泛关注,但其潜在机制尚不清楚。
在本研究中,采用睾丸形态测量和约翰森评分来评估睾丸损伤程度。然后使用双荧光素酶报告基因检测法验证MeCP2的上游转录因子。最后,检测C/EBP-β、MeCP2和Wnt4/β-连环蛋白的蛋白表达,以阐明调控途径。
在微重力条件下,大鼠睾丸中MeCP2表达显著降低,且与睾丸形态测量指标呈正相关。随后,双荧光素酶报告基因检测显示C/EBP-β直接与MeCP2的启动子序列结合,启动其转录活性。同时,在微重力条件下,睾丸中C/EBP-β、Wnt4和β-连环蛋白的表达降低。
总之,我们的研究表明C/EBP-β调控MeCP2,进而抑制Wnt4/β-连环蛋白途径活性,从而参与微重力诱导的睾丸损伤。