Stra8, short for Stimulated by Retinoic Acid Gene 8, is a crucial gene in vertebrates. It functions as an essential gatekeeper of meiotic initiation, playing a vital role in the transition from mitotic to meiotic cell cycles, which is crucial for haploid gamete formation and fertility. Stra8 is induced by retinoic acid (RA) and is involved in pathways related to spermatogonial development, cell cycle regulation, and apoptosis regulation [4,5,6]. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying Stra8's functions.

In female mice, mutation of the RB-binding site of Stra8 delays meiotic entry, meiotic prophase progression, and leads to precocious depletion of the oocyte pool, indicating that the Stra8-RB interaction is required for S phase entry, meiotic gene activation, and precise timing of meiosis initiation in oocytes [1]. In male mice, Stra8 knockout leads to a muted RA response in spermatogonia, with more transcripts typical of undifferentiated cells and fewer of differentiating cells, and spermatocytes fail to complete meiosis, suggesting that Stra8 is important for transcriptional changes during spermatogonial development [2]. Additionally, Stra8-deficient germ cells in male mice fail to enter meiosis and show aberrant upregulation of autophagy-lysosome genes with autophagy activation, and Stra8 may inhibit apoptosis during spermatogenesis via the AKT signaling pathway [6,7].

In conclusion, Stra8 is essential for meiotic initiation in both male and female germ cells. Studies using KO mouse models have revealed its roles in processes like spermatogonial development, meiosis timing, autophagy regulation, and apoptosis inhibition. These findings contribute to our understanding of infertility-related diseases, especially premature ovarian insufficiency where pathogenic mutations in Stra8 may be involved [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. 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/

6. 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/

7. 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/