• PMID: 30322389
• Gene Name: Nanos2
• Condition: Male infertility, cryptorchidism
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility, cryptorchidism

miR-34c disrupts spermatogonial stem cell homeostasis in cryptorchid testes by targeting Nanos2

Huang Z, Tang D, Gao J, Dou X, Cheng P, Peng D, Zhang Y, Mao J, Zhang L, Zhang X.

BACKGROUND: Cryptorchidism as a common genitourinary malformation with the serious complication of male infertility draws widespread attention. With several reported miRNAs playing critical roles in spermatogonial stem cells (SSCs), we aimed to explore the fundamental function of the highly conserved miR-34c in cryptorchidism. METHODS: To explore whether miR-34c participates in spermatogenesis by regulating Nanos2, we examined the effect of overexpression and inhibition for miR-34c on Nanos2 expression in GC-1 cells. Moreover, the expression levels of miR-34c and Nanos2 with cryptorchidism in humans and mice were examined. Furthermore, the homeostasis of SSCs was evaluated through counting the number of promyelocytic leukemia zinc finger (PLZF) positive spermatogonia in murine cryptorchid testes. RESULTS: In the present study, we show that miR-34c could inhibit the expression of Nanos2 in GC-1 cells. Meanwhile, miR-34c significantly decreased in both the testicular tissues of patients with cryptorchidism and surgery-induced murine model of cryptorchidism. Western blot revealed that the protein level of Nanos2 was up-regulated and showed to be negatively correlated to the expression of miR-34c in our model. The abnormal expression of miR-34c/Nanos2 disrupted the balance between SSC self-renewal and differentiation, eventually damaging the spermatogenesis of cryptorchid testes. CONCLUSIONS: The miR-34c/Nanos2 pathway provides new insight into the mechanism of male infertility caused by cryptorchidism. Our results indicate that miR-34c may serve as a biological marker for treatment of infertility caused by cryptorchidism. FAU - Huang, Zhenyu AU - Huang Z AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Tang, Dongdong AU - Tang D AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. AD - Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, 230032, China. AD - Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei, 230022, China. FAU - Gao, Jingjing AU - Gao J AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Dou, Xianming AU - Dou X AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Cheng, Peng AU - Cheng P AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Peng, Dangwei AU - Peng D AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Zhang, Yao AU - Zhang Y AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Mao, Jun AU - Mao J AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Zhang, Li AU - Zhang L AD - Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.