Stra8, short for Stimulated by Retinoic Acid Gene 8, is a key gene in the transition of mammalian germ cells from mitosis to meiosis. It is induced by retinoic acid (RA) signaling and is essential for meiotic initiation in both male and female germ cells. Stra8 is involved in regulating spermatogonial proliferation, differentiation, and meiosis, and it also has a role in ovarian development and function [4,5,6,7]. Gene knockout (KO) mouse models have been crucial in understanding its function.

In female KO mice, mutation of the RB-binding site of Stra8 delays meiotic entry, meiotic prophase progression, and leads to precocious depletion of the oocyte pool, suggesting that the Stra8-RB interaction is required for S phase entry and meiotic gene activation [1]. In male Stra8 knockout mice, spermatogonia display a muted response to RA, with more transcripts typical of undifferentiated cells and fewer of differentiating cells, and ultimately, spermatocytes fail to complete meiosis [2]. Stra8-deficient male germ cells also show aberrant upregulation of autophagy-lysosome genes and activation of autophagy, while Stra8 overexpression inhibits apoptosis in male germ cells [8,9].

In conclusion, Stra8 is a vital gatekeeper for meiotic initiation in vertebrates. Through studies using KO mouse models, we've learned that it plays a significant role in regulating the cell cycle, apoptosis, and autophagy during spermatogenesis and oogenesis. Its dysfunction may be associated with conditions like premature ovarian insufficiency, highlighting its importance in understanding infertility-related diseases [3].

References:

1. Shimada, Ryuki, Kato, Yuzuru, Takeda, Naoki, Araki, Kimi, Ishiguro, Kei-Ichiro. 2023. STRA8-RB interaction is required for timely entry of meiosis in mouse female germ cells. In Nature communications, 14, 6443. doi:10.1038/s41467-023-42259-6. https://pubmed.ncbi.nlm.nih.gov/37880249/

2. Gewiss, Rachel L, Shelden, Eric A, Griswold, Michael D. 2021. STRA8 induces transcriptional changes in germ cells during spermatogonial development. In Molecular reproduction and development, 88, 128-140. doi:10.1002/mrd.23448. https://pubmed.ncbi.nlm.nih.gov/33400349/

3. Ke, Hanni, Tang, Shuyan, Guo, Ting, Jin, Li, Chen, Zi-Jiang. 2023. Landscape of pathogenic mutations in premature ovarian insufficiency. In Nature medicine, 29, 483-492. doi:10.1038/s41591-022-02194-3. https://pubmed.ncbi.nlm.nih.gov/36732629/

4. Lu, Xia-Ying, Yang, Bei, Xu, Si-Fan, Zou, Ting. . [STRA8 as a specific expression marker in postnatal male germ cells]. In Zhonghua nan ke xue = National journal of andrology, 16, 161-5. doi:. https://pubmed.ncbi.nlm.nih.gov/20369703/

5. Ishiguro, Kei-Ichiro, Matsuura, Kumi, Tani, Naoki, Araki, Kimi, Niwa, Hitoshi. 2020. MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells. In Developmental cell, 52, 429-445.e10. doi:10.1016/j.devcel.2020.01.010. https://pubmed.ncbi.nlm.nih.gov/32032549/

6. Niu, Changmin, Guo, Jiaqian, Shen, Xueyi, Xia, Jing, Zheng, Ying. 2020. Meiotic gatekeeper STRA8 regulates cell cycle by interacting with SETD8 during spermatogenesis. In Journal of cellular and molecular medicine, 24, 4194-4211. doi:10.1111/jcmm.15080. https://pubmed.ncbi.nlm.nih.gov/32090428/

7. Ishiguro, Kei-Ichiro. 2024. Mechanisms of meiosis initiation and meiotic prophase progression during spermatogenesis. In Molecular aspects of medicine, 97, 101282. doi:10.1016/j.mam.2024.101282. https://pubmed.ncbi.nlm.nih.gov/38797021/

8. Shen, Xueyi, Niu, Changmin, Guo, Jiaqian, Hu, Yanqiu, Zheng, Ying. 2018. Stra8 may inhibit apoptosis during mouse spermatogenesis via the AKT signaling pathway. In International journal of molecular medicine, 42, 2819-2830. doi:10.3892/ijmm.2018.3825. https://pubmed.ncbi.nlm.nih.gov/30106128/

9. Ferder, Ianina C, Fung, Leslie, Ohguchi, Yasuyo, Xavier, Ramnik J, Wang, Ning. 2019. Meiotic gatekeeper STRA8 suppresses autophagy by repressing Nr1d1 expression during spermatogenesis in mice. In PLoS genetics, 15, e1008084. doi:10.1371/journal.pgen.1008084. https://pubmed.ncbi.nlm.nih.gov/31059511/