Abstract
Spermatogenesis, the process by which haploid sperm cells are produced from a diploid precursor cell, is essential for sexual reproduction. Here, we report that RING-finger protein 138 (Rnf138) is highly expressed in testes, especially in spermatogonia and spermatocytes. The role of Rnf138 in spermatogenesis was examined using a Rnf138-knockout mouse model. Rnf138 deficiency resulted in increased apoptosis in spermatogenic cells, loss of proliferative spermatogonia, delayed development of spermatozoa and impaired fertility. The proportion of PLZF+Ki67+ cells within the PLZF+ population decreased in the knockout mice. The phenotype was further assessed by RNA-sequencing (RNA-seq), which determined that the expression levels of many genes involved in spermatogenesis were altered in the testis of Rnf138-knockout mice. Thus, Rnf138 deficiency promotes the apoptosis of spermatogenic cells, which may have been caused by the aberrant proliferation of spermatogonia in mouse testis development.
Highlights
Spermatogenesis is a complex process comprised of sequential mitotic, meiotic and spermiogenic phases.[1]
By comparing the testes staining between Rnf138fl/fl and Rnf138−/− at 7 weeks, the results showed that RING-finger protein 138 (RNF138) was mainly expressed in the spermatogonia and spermatocytes (Figure 2e)
E3 ligases have been reported to have an important role in testis development and spermatogenesis
Summary
Spermatogenesis is a complex process comprised of sequential mitotic, meiotic and spermiogenic phases.[1]. The gene encoding the RING-finger protein 138 (RNF138), known as HSD-4 or NARF, was first isolated in our lab from a human testis-subtracted cDNA library in 1999 (GenBank: AF162680.3) It contains an N-terminal C3HC4 (Cys(3)-HisCys(4)) RING domain, three zinc-finger-like domains and a C-terminal UIM-type (ubiquitin-interacting motif) domain.[13] RNF138 has been shown to function as an E3 ligase in the regulation of Wnt-β-catenin signaling by interacting with the negative regulator NLK to target the Wnt-activating cofactor TCF/LEF for degradation by ubiquitination.[14] two recent studies discovered that RNF138 is a key homologous recombination (HR)-promoting factor that regulates DNA repair by displacing Ku and ubiquitinating CtIP.[15,16] Even though Rnf[138] was first identified in testes, its role in spermatogenesis has not yet been studied. We discussed the role of Rnf[138] in regulating the apoptosis of proliferative spermatogonia
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