Psma8, also known as α4s, is a testis-specific proteasomal subunit. The proteasome is a key component in the ubiquitin-proteasome system, which is involved in protein degradation and thus regulates various biological processes. Psma8-associated proteasomes play a crucial role in spermatogenesis, especially in the degradation of meiotic proteins and the progression of meiosis I [1,2,3].

In Psma8-deficient mouse models, several significant phenotypes are observed. Meiotic proteins such as RAD51 and RPA1, which are normally degraded at late prophase I, remain stable in Psma8-deleted spermatocytes. Psma8-null spermatocytes show delayed M-phase entry and are eventually arrested at this stage. This leads to an accumulation of spermatocytes in metaphase I and II, which either enter apoptosis or give rise to a low number of aberrant round spermatids that apoptose before histone replacement, resulting in male infertility [1,2]. Additionally, in these models, the proteostasis of several key meiotic players that interact with PSMA8, like SYCP3, SYCP1, CDK1 and TRIP13, is altered [1].

In conclusion, Psma8 is essential for proper meiotic exit during spermatogenesis and male fertility. The study of Psma8-deficient mouse models has significantly enhanced our understanding of male infertility, potentially providing targets for male contraception or treatment of male infertility [1,2,3].

References:

1. Gómez-H, Laura, Felipe-Medina, Natalia, Condezo, Yazmine B, Llano, Elena, Pendas, Alberto M. 2019. The PSMA8 subunit of the spermatoproteasome is essential for proper meiotic exit and mouse fertility. In PLoS genetics, 15, e1008316. doi:10.1371/journal.pgen.1008316. https://pubmed.ncbi.nlm.nih.gov/31437213/

2. Zhang, Qianting, Ji, Shu-Yan, Busayavalasa, Kiran, Shao, Jingchen, Yu, Chao. 2019. Meiosis I progression in spermatogenesis requires a type of testis-specific 20S core proteasome. In Nature communications, 10, 3387. doi:10.1038/s41467-019-11346-y. https://pubmed.ncbi.nlm.nih.gov/31358751/

3. Zhang, Zi-Hui, Jiang, Tian-Xia, Chen, Lian-Bin, Gao, Fei, Qiu, Xiao-Bo. 2020. Proteasome subunit α4s is essential for formation of spermatoproteasomes and histone degradation during meiotic DNA repair in spermatocytes. In The Journal of biological chemistry, 296, 100130. doi:10.1074/jbc.RA120.016485. https://pubmed.ncbi.nlm.nih.gov/33262216/