The microRNA miR-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis

ABSTRACT Spermatogonial differentiation and meiotic initiation during spermatogenesis are tightly regulated by a number of genes, including those encoding enzymes for miRNA biogenesis. However, whether and how single miRNAs regulate these processes remain unclear. Here, we report that miR-202, a member of the let-7 family, prevents precocious spermatogonial differentiation and meiotic initiation in spermatogenesis by regulating the timely expression of many genes, including those for key regulators such as STRA8 and DMRT6. In miR-202 knockout (KO) mice, the undifferentiated spermatogonial pool is reduced, accompanied by age-dependent decline of fertility. In KO mice, SYCP3, STRA8 and DMRT6 are expressed earlier than in wild-type littermates, and Dmrt6 mRNA is a direct target of miR-202-5p. Moreover, the precocious spermatogonial differentiation and meiotic initiation were also observed in KO spermatogonial stem cells when cultured and induced in vitro, and could be partially rescued by the knockdown of Dmrt6. Therefore, we have not only shown that miR-202 is a regulator of meiotic initiation but also identified a previously unknown module in the underlying regulatory network.

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MicroRNA-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis

10.1101/2021.06.27.449895 ◽

2021 ◽

Author(s):

Jian Chen ◽

Chenxu Gao ◽

Xiwen Lin ◽

Yan Ning ◽

Wei He ◽

...

Keyword(s):

Stem Cells ◽

Regulatory Network ◽

Spermatogonial Stem Cells ◽

Mirna Biogenesis ◽

Seminiferous Tubules ◽

Wild Type ◽

Number Of Genes ◽

Direct Target ◽

Meiotic Initiation

Spermatogonial differentiation and meiotic initiation during spermatogenesis are tightly regulated by a number of genes including those coding enzymes for miRNA biogenesis. However, whether and how single miRNAs regulate these processes remain unclear. Here, we report that miR-202, a member of the let-7 family, prevents precocious spermatogonial differentiation and meiotic initiation in spermatogenesis by regulating the timely expression of many genes including those for other key regulators. In miR-202 knockout (KO) mice, the undifferentiated spermatogonial pool is reduced, ultimately causing agametic seminiferous tubules. SYCP3, STRA8 and DMRT6 are expressed earlier in KO mice than in wild-type (WT) littermates, and Dmrt6 mRNA is a direct target of miR-202-5p. Moreover, the precocious spermatogonial differentiation and meiotic initiation were also observed in KO spermatogonial stem cells when cultured and induced in vitro, and could be rescued by the knockdown of Dmrt6. Therefore, we have not only shown that miR-202 is a novel regulator of meiotic initiation but also added a new module to the underlying regulatory network.

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In vitro differentiation of spermatogonial stem cells to functional sperm in zebrafish

Reproduction Abstracts ◽

10.1530/repabs.1.p356 ◽

2014 ◽

Author(s):

Noriyoshi Sakai

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells ◽

In Vitro Differentiation

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Homing of mouse spermatogonial stem cells on acellular testis following in vitro transplantation.

10.26226/morressier.5af300b3738ab10027aa9b14 ◽

2018 ◽

Author(s):

Mansoureh Movahedin

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells

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In Vitro Propagation of Human Prepubertal Spermatogonial Stem Cells

JAMA ◽

10.1001/jama.2011.791 ◽

2011 ◽

Vol 305 (23) ◽

pp. 2416 ◽

Cited By ~ 139

Author(s):

Hooman Sadri-Ardekani

Keyword(s):

Stem Cells ◽

In Vitro Propagation ◽

Spermatogonial Stem Cells

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Propagation of bovine spermatogonial stem cells in vitro

Reproduction ◽

10.1530/rep-07-0419 ◽

2008 ◽

Vol 136 (5) ◽

pp. 543-557 ◽

Cited By ~ 90

Author(s):

Pedro M Aponte ◽

Takeshi Soda ◽

Katja J Teerds ◽

S Canan Mizrak ◽

Henk J G van de Kant ◽

...

Keyword(s):

Stem Cells ◽

Growth Factor ◽

Cultured Cells ◽

Somatic Cells ◽

Type A ◽

Spermatogonial Stem Cells ◽

Seminiferous Tubules ◽

Type A Spermatogonia ◽

Stimulation Of

The access to sufficient numbers of spermatogonial stem cells (SSCs) is a prerequisite for the study of their regulation and further biomanipulation. A specialized medium and several growth factors were tested to study thein vitrobehavior of bovine type A spermatogonia, a cell population that includes the SSCs and can be specifically stained for the lectin Dolichos biflorus agglutinin. During short-term culture (2 weeks), colonies appeared, the morphology of which varied with the specific growth factor(s) added. Whenever the stem cell medium was used, round structures reminiscent of sectioned seminiferous tubules appeared in the core of the colonies. Remarkably, these round structures always contained type A spermatogonia. When leukemia inhibitory factor (LIF), epidermal growth factor (EGF), or fibroblast growth factor 2 (FGF2) were added, specific effects on the numbers and arrangement of somatic cells were observed. However, the number of type A spermatogonia was significantly higher in cultures to which glial cell line-derived neurotrophic factor (GDNF) was added and highest when GDNF, LIF, EGF, and FGF2 were all present. The latter suggests that a proper stimulation of the somatic cells is necessary for optimal stimulation of the germ cells in culture. Somatic cells present in the colonies included Sertoli cells, peritubular myoid cells, and a few Leydig cells. A transplantation experiment, using nude mice, showed the presence of SSCs among the cultured cells and in addition strongly suggested a more than 10 000-fold increase in the number of SSCs after 30 days of culture. These results demonstrate that bovine SSC self-renew in our specialized bovine culture system and that this system can be used for the propagation of these cells.

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