Mouse Tspyl5 promotes spermatogonia proliferation through enhancing Pcna-mediated DNA replication
Xiangyou Leng
A , Shengyu Xie A , Dachang Tao A , Zhaokun Wang A , Jiaying Shi A , Ming Yi A , Xiaolan Tan A , Xinyue Zhang A , Yunqiang Liu A * and Yuan Yang A *
A
Abstract
The human TSPY1 (testis-specific protein, Y-linked 1) gene is critical for spermatogenesis and male fertility. However, there have been difficulties with studying the mechanism underlying its function, partly due to the presence of the Tspy1 pseudogene in mice.
TSPYL5 (TSPY-like 5), an autosomal homologous gene of TSPY1 showing a similar expression pattern in both human and mouse testes, is also speculated to play a role in male spermatogenesis. It is beneficial to understand the role of TSPY1 in spermatogenesis by investigating Tspyl5 functions.
Tspyl5-knockout mice were generated to investigate the effect of TSPYL5 knockout on spermatogenesis.
Tspyl5 deficiency caused a decline in fertility and decreased the numbers of spermatogonia and spermatozoa in aged male mice. Trancriptomic detection of spermatogonia derived from aged Tspyl5-knockout mice revealed that the Pcna-mediated DNA replication pathway was downregulated. Furthermore, Tspyl5 was proven to facilitate spermatogonia proliferation and upregulate Pcna expression by promoting the ubiquitination-degradation of the TRP53 protein.
Our findings suggest that Tspyl5 is a positive regulator for the maintenance of the spermatogonia pool by enhancing Pcna-mediated DNA replication.
This observation provides an important clue for further investigation of the spermatogenesis-related function of TSPY1.
Keywords: age-related male infertility, CRISPR/Cas9 technology, DNA replication, Pcna, Spermatogonia, transcriptomic analysis, TRP53, Tspyl5.
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