Dataset Information

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

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 Rad51 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.

SUBMITTER: Gao H

PROVIDER: S-EPMC6591449 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gao Huihui H Wen Hui H Cao Congcong C Dong Daqian D Yang Chenhao C Xie Shengsong S Zhang Jin J Huang Xunbin X Huang Xingxu X Yuan Shuiqiao S Dong Wuzi W

Frontiers in physiology 20190618

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 ...[more]

PMID: 31275170

Similar Datasets

Project description:Mutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling germ cell development. The RNA-binding protein and E3 ubiquitin ligase TRIM71 is essential for embryogenesis, and its expression has been reported in GCT and adult mouse testes. To investigate the role of TRIM71 in mammalian germ cell embryonic development, we generated a germline-specific conditional Trim71 knockout mouse (cKO) using the early primordial germ cell (PGC) marker Nanos3 as a Cre-recombinase driver. cKO mice are infertile, with male mice displaying a Sertoli cell-only (SCO) phenotype which in humans is defined as a specific subtype of non-obstructive azoospermia characterized by the absence of germ cells in the seminiferous tubules. Infertility in male Trim71 cKO mice originates during embryogenesis, as the SCO phenotype was already apparent in neonatal mice. The in vitro differentiation of mouse embryonic stem cells (ESCs) into PGC-like cells (PGCLCs) revealed reduced numbers of PGCLCs in Trim71-deficient cells. Furthermore, TCam-2 cells, a human GCT-derived seminoma cell line which was used as an in vitro model for PGCs, showed proliferation defects upon TRIM71 knockdown. Additionally, in vitro growth competition assays, as well as proliferation assays with wild type and CRISPR/Cas9-generated TRIM71 mutant NCCIT cells showed that TRIM71 also promotes proliferation in this malignant GCT-derived non-seminoma cell line. Importantly, the PGC-specific markers BLIMP1 and NANOS3 were consistently downregulated in Trim71 KO PGCLCs, TRIM71 knockdown TCam-2 cells and TRIM71 mutant NCCIT cells. These data collectively support a role for TRIM71 in PGC development. Last, via exome sequencing analysis, we identified several TRIM71 variants in a cohort of infertile men, including a loss-of-function variant in a patient with an SCO phenotype. Altogether, our work reveals for the first time an association of TRIM71 deficiency with human male infertility, and uncovers further developmental roles for TRIM71 in the germline during mouse embryogenesis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets