TY - JOUR
T1 - C/EBP-β/MeCP2/Wnt Axis Participates in the Testicular Injury in Rats Under Simulated Microgravity Conditions
AU - Ge, Pan
AU - Wang, Si Yu
AU - Zhang, Xiang
AU - Yang, Yan Qi
AU - Lv, Mo Qi
AU - Sun, Ying
AU - Zhang, Jian
AU - Wang, Xiao Ting
AU - Liu, Ming
AU - Zhou, Dang Xia
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Society for Reproductive Investigation 2025.
PY - 2025/10
Y1 - 2025/10
N2 - Background and Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Background and Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - C/EBP-β
KW - MeCP2
KW - Microgravity
KW - Testicular injury
KW - Wnt4/β-Catenin pathway
UR - https://www.scopus.com/pages/publications/105015526825
U2 - 10.1007/s43032-025-01965-w
DO - 10.1007/s43032-025-01965-w
M3 - 文章
C2 - 40913202
AN - SCOPUS:105015526825
SN - 1933-7191
VL - 32
SP - 3349
EP - 3360
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 10
ER -