Dataset Information

CDKN2AIP is critical for spermiogenesis and germ cell development.

ABSTRACT:

Background

As a member of RNA-binding protein, CDKN2AIP has been shown to play a critical role in stem cell pluripotency and somatic differentiation. Recent studies indicate that Cdkn2aip is essential for spermatogonial self-renewal and proliferation through the activating Wnt-signaling pathway. However, the mechanisms of how Cdkn2aip regulate spermatogenesis is poorly characterized.

Results

We discovered that the CDKN2AIP was expressed in spermatocyte as well as spermatids and participated in spermiogenesis. Cdkn2aip^-/- mice exhibited multiple sperm head defects accompanied by age dependent germ cell loss that might be result of protamine replacement failure and impaired SUN1 expression. Loss of Cdkn2aip expression in male mice resulted in synapsis failure in 19% of all spermatocytes and increased apoptosis due to damaged DNA double-strand break (DSB) repair and crossover formation. In vitro, knockdown of Cdkn2aip was associated with extended S phase, increased DNA damage and apoptosis.

Conclusions

Our findings not only identified the importance of CDKN2AIP in spermiogenesis and germ cell development, but also provided insight upon the driving mechanism.

SUBMITTER: Cao Y

PROVIDER: S-EPMC9394077 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

CDKN2AIP is critical for spermiogenesis and germ cell development.

Cao Yuming Y Sun Qi Q Chen Zhenlie Z Lu Jing J Geng Ting T Ma Ling L Zhang Yuanzhen Y

Cell & bioscience 20220821 1

<h4>Background</h4>As a member of RNA-binding protein, CDKN2AIP has been shown to play a critical role in stem cell pluripotency and somatic differentiation. Recent studies indicate that Cdkn2aip is essential for spermatogonial self-renewal and proliferation through the activating Wnt-signaling pathway. However, the mechanisms of how Cdkn2aip regulate spermatogenesis is poorly characterized.<h4>Results</h4>We discovered that the CDKN2AIP was expressed in spermatocyte as well as spermatids and pa ...[more]

PMID: 35989335

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Project description:Meiosis expressed gene 1 (Meig1) was originally identified in a search for mammalian genes potentially involved in meiosis. Seven mouse Meig1 transcripts with the same coding region, but different 5'-UTRs, have been identified. These transcripts have different tissue distributions, two are only present in the testis. In the testis, Meig1 is present in germ cells and Sertoli cells. A Meig1 conditional knockout model has been generated. When Meig1 was inactivated globally by crossing with Cmv-Cre transgenic mice, the Meig1-deficient males were sterile due to severe spermiogenic defects, and had no obvious defects in meiosis. To further study its role in individual cell types in the testis, the Meig1(flox) mice were crossed with Hsp2a-Cre, Prm-Cre, and Amh-Cre mice, in which the Cre recombinase is driven by the heat shock protein 2 (Hsp2a) gene promoter (expressed in spermatocytes), the protamine 1 gene promoter (expressed in post-meiotic spermatids) and the anti-Mullerian hormone (Amh) gene promoter (expressed in Sertoli cells) respectively. Both Meig1 mRNA and protein were undetectable in testis of the Hsp2a-Cre; Meig1(flox/flox) mice and all the mutant adult males tested were sterile. This phenotype mirrors that of the Cmv-Cre; Meig1(flox/flox) mice. Even though the total testicular Meig1 mRNA and protein expression levels were dramatically reduced in testis of the Prm-Cre; Meig1(flox/flox) males, all the mice tested were fertile, and there was no significant difference in sperm count and sperm motility compared with age-matched Meig1(flox/flox) male mice. Disruption of Meig1 in the Sertoli cells did not affect the MEIG1 protein expression. Amh-Cre; Meig1(flox/flox) males were fertile, and produced the same amount of spermatozoa as age-matched Meig1(flox/flox) mice. The testicular histology was also normal. Our results indicate that MEIG1 regulates spermiogenesis through effects in germ cells alone, and that the Meig1 gene must be active during a discrete period in spermatogenesis after which it is dispensable.

Dataset Information

CDKN2AIP is critical for spermiogenesis and germ cell development.

Background

Results

Conclusions

Publications

CDKN2AIP is critical for spermiogenesis and germ cell development.

Similar Datasets

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