Nanos2 is a member of the Nanos gene family, encoding an evolutionarily conserved RNA-binding protein. It is a male-germ-cell-specific gene. During embryonic development, it promotes male primordial germ cell (PGC) development and inhibits their entry into meiosis. In spermatogenesis, it suppresses spermatogonial stem cell (SSC) differentiation, maintaining the SSC pool's stability. Nanos2 is also involved in specific RNA degradation and may be associated with male reproductive system diseases [1,2].

Gene knockout studies in male mice have provided crucial insights into Nanos2's function. Knocking out Nanos2 leads to the disappearance of germ cells and male infertility, highlighting its essential role in male germ cell survival [1]. In addition, overexpression of Nanos2 in the testis causes an accumulation of SSCs in seminiferous tubules, indicating its role in regulating SSC differentiation [1]. Single-cell RNA sequencing of wild-type and Nanos2-KO testes revealed that Nanos2 expression starts in mitotic cells and induces mitotic arrest, suggesting it suppresses the cell cycle by repressing mTORC1 activators like Rheb post-transcriptionally [3].

In conclusion, Nanos2 is vital for male germ cell development and spermatogenesis. Mouse models with Nanos2 knockout or overexpression have clearly demonstrated its role in maintaining germ cell populations, regulating the cell cycle, and differentiating male germ cells. Understanding Nanos2's function may contribute to uncovering the mechanisms underlying male reproductive system diseases and developing potential therapeutic strategies.

References:

1. Huang, Zhen-Yu, Zhang, Xian-Sheng. . [Nanos2 in the male reproductive system: Progress in studies]. In Zhonghua nan ke xue = National journal of andrology, 24, 558-561. doi:. https://pubmed.ncbi.nlm.nih.gov/30173464/

2. Saga, Yumiko. 2010. Function of Nanos2 in the male germ cell lineage in mice. In Cellular and molecular life sciences : CMLS, 67, 3815-22. doi:10.1007/s00018-010-0456-x. https://pubmed.ncbi.nlm.nih.gov/20652721/

3. Shimada, Ryuki, Koike, Hiroko, Hirano, Takamasa, Kato, Yuzuru, Saga, Yumiko. 2021. NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells. In iScience, 24, 102890. doi:10.1016/j.isci.2021.102890. https://pubmed.ncbi.nlm.nih.gov/34401671/