Overexpression of MicroRNA-10a in Germ Cells Causes Male Infertility by Targeting Rad51 in Mouse and Human

Overview

Journal Front Physiol

Date 2019 Jul 6

PMID 31275170

Citations 22

Authors

Huihui Gao

Hui Wen

Congcong Cao

Daqian Dong

Chenhao Yang

Shengsong Xie

Jin Zhang

Xunbin Huang

Xingxu Huang

Shuiqiao Yuan

Wuzi Dong

Affiliations

Soon will be listed here.

Abstract

Spermatogenesis is a complicated process including spermatogonial stem cells self-renewal and differentiates into mature spermatozoa. MicroRNAs (miRNAs) as a class of small non-coding RNAs play a crucial role during the process of spermatogenesis. However, the function of a plenty of miRNAs on spermatogenesis and the potential mechanisms remain largely unknown. Here, we show that genetically conditional overexpressed miR-10a in germ cells caused complete male sterility, characterized by meiotic arrested in germ cells. Analysis of miR-10a overexpression mouse testes reveals that failure of double strand break (DSB) repairs and aberrant spermatogonial differentiation. Furthermore, we identified as a key target of miR-10a in germ cell by bioinformatics prediction and luciferase assay, which may be responsible for the infertility of the miR-10a overexpressed mice and germ cell arrested patients. Our data show that miR-10a dependent genetic regulation of meiotic process is crucial for male germ cell development and spermatogenesis in both mouse and human. These findings facilitate our understanding of the roles of miRNA-10a in spermatogenesis and male fertility.

Citing Articles

The microRNA-mediated apoptotic signaling axis in male reproduction: a possible and targetable culprit in male infertility.

Yu P, Zhao X, Zhou D, Wang S, Hu Z, Lian K Cell Biol Toxicol. 2025; 41(1):54.

PMID: 40038116 PMC: 11880093. DOI: 10.1007/s10565-025-10006-w.

Harnessing the power of miRNAs for precision diagnosis and treatment of male infertility.

Doghish A, Elsakka E, Ahmed Mohamed Moustafa H, Ashraf A, Mageed S, Mohammed O Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39535597 DOI: 10.1007/s00210-024-03594-7.

Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation.

Moayeri M, Irani S, Novin M, Salahshourifar I, Salehi M Reprod Sci. 2024; 31(10):3112-3121.

PMID: 39014289 DOI: 10.1007/s43032-024-01640-6.

Effects of Slow Freezing and Vitrification of Human Semen on Post-Thaw Semen Quality and miRNA Expression.

Podgrajsek R, Bolha L, Pungert T, Pizem J, Jazbec K, Malicev E Int J Mol Sci. 2024; 25(8).

PMID: 38673743 PMC: 11050687. DOI: 10.3390/ijms25084157.

MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers.

Shi Z, Yu M, Guo T, Sui Y, Tian Z, Ni X Front Endocrinol (Lausanne). 2024; 15:1293368.

PMID: 38449855 PMC: 10916303. DOI: 10.3389/fendo.2024.1293368.

References

Pelttari J, Hoja M, Yuan L, Liu J, Brundell E, Moens P . A meiotic chromosomal core consisting of cohesin complex proteins recruits DNA recombination proteins and promotes synapsis in the absence of an axial element in mammalian meiotic cells. Mol Cell Biol. 2001; 21(16):5667-77. PMC: 87287. DOI: 10.1128/MCB.21.16.5667-5677.2001. View

Carrington J, Ambros V . Role of microRNAs in plant and animal development. Science. 2003; 301(5631):336-8. DOI: 10.1126/science.1085242. View

Petukhova G, Pezza R, Vanevski F, Ploquin M, Masson J, Camerini-Otero R . The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination. Nat Struct Mol Biol. 2005; 12(5):449-53. DOI: 10.1038/nsmb923. View

de Vries F, de Boer E, van den Bosch M, Baarends W, Ooms M, Yuan L . Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation. Genes Dev. 2005; 19(11):1376-89. PMC: 1142560. DOI: 10.1101/gad.329705. View

Kolas N, Marcon E, A Crackower M, Hoog C, Penninger J, Spyropoulos B . Mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or X-Y defective male-specific sterility. Chromosoma. 2005; 114(2):92-102. DOI: 10.1007/s00412-005-0334-8. View

Gregory R, Chendrimada T, Cooch N, Shiekhattar R . Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005; 123(4):631-40. DOI: 10.1016/j.cell.2005.10.022. View

Chen C, Ridzon D, Broomer A, Zhou Z, Lee D, Nguyen J . Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005; 33(20):e179. PMC: 1292995. DOI: 10.1093/nar/gni178. View

Koubova J, Menke D, Zhou Q, Capel B, Griswold M, Page D . Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A. 2006; 103(8):2474-9. PMC: 1413806. DOI: 10.1073/pnas.0510813103. View

Gallardo T, Shirley L, John G, Castrillon D . Generation of a germ cell-specific mouse transgenic Cre line, Vasa-Cre. Genesis. 2007; 45(6):413-7. PMC: 2597027. DOI: 10.1002/dvg.20310. View

10.

Hayashi K, Chuva de Sousa Lopes S, Kaneda M, Tang F, Hajkova P, Lao K . MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One. 2008; 3(3):e1738. PMC: 2254191. DOI: 10.1371/journal.pone.0001738. View

11.

Agirre X, Jimenez-Velasco A, Jose-Eneriz E, Garate L, Bandres E, Cordeu L . Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth. Mol Cancer Res. 2008; 6(12):1830-40. DOI: 10.1158/1541-7786.MCR-08-0167. View

12.

Weiss F, Marques I, Woltering J, Vlecken D, Aghdassi A, Partecke L . Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer. Gastroenterology. 2009; 137(6):2136-45.e1-7. DOI: 10.1053/j.gastro.2009.08.065. View

13.

Huang H, Xie C, Sun X, Ritchie R, Zhang J, Chen Y . miR-10a contributes to retinoid acid-induced smooth muscle cell differentiation. J Biol Chem. 2010; 285(13):9383-9389. PMC: 2843187. DOI: 10.1074/jbc.M109.095612. View

14.

Bouhallier F, Allioli N, Lavial F, Chalmel F, Perrard M, Durand P . Role of miR-34c microRNA in the late steps of spermatogenesis. RNA. 2010; 16(4):720-31. PMC: 2844620. DOI: 10.1261/rna.1963810. View

15.

Xie S, Li X, Liu T, Cao J, Zhong Q, Zhao S . Discovery of porcine microRNAs in multiple tissues by a Solexa deep sequencing approach. PLoS One. 2011; 6(1):e16235. PMC: 3026822. DOI: 10.1371/journal.pone.0016235. View

16.

Dray E, Dunlop M, Kauppi L, San Filippo J, Wiese C, Tsai M . Molecular basis for enhancement of the meiotic DMC1 recombinase by RAD51 associated protein 1 (RAD51AP1). Proc Natl Acad Sci U S A. 2011; 108(9):3560-5. PMC: 3048120. DOI: 10.1073/pnas.1016454108. View

17.

Idler R, Yan W . Control of messenger RNA fate by RNA-binding proteins: an emphasis on mammalian spermatogenesis. J Androl. 2011; 33(3):309-37. PMC: 5441524. DOI: 10.2164/jandrol.111.014167. View

18.

Niu Z, Goodyear S, Rao S, Wu X, Tobias J, Avarbock M . MicroRNA-21 regulates the self-renewal of mouse spermatogonial stem cells. Proc Natl Acad Sci U S A. 2011; 108(31):12740-5. PMC: 3150879. DOI: 10.1073/pnas.1109987108. View

19.

Chang Y, Lee-Chang J, Panneerdoss S, MacLean 2nd J, Rao M . Isolation of Sertoli, Leydig, and spermatogenic cells from the mouse testis. Biotechniques. 2011; 51(5):341-2, 344. PMC: 3774005. DOI: 10.2144/000113764. View

20.

Tong M, Mitchell D, McGowan S, Evanoff R, Griswold M . Two miRNA clusters, Mir-17-92 (Mirc1) and Mir-106b-25 (Mirc3), are involved in the regulation of spermatogonial differentiation in mice. Biol Reprod. 2011; 86(3):72. PMC: 3316268. DOI: 10.1095/biolreprod.111.096313. View