A Novel Testis-enriched Gene, , Regulates Spermatogenesis As a Spermatid-specific Factor

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Oct 24

PMID 36274854

Authors

Jinsoo Ahn

Dong-Hwan Kim

Mi-Ryung Park

Yeunsu Suh

Haesun Lee

Seongsoo Hwang

Lovelia L Mamuad

Sang Suk Lee

Kichoon Lee

Affiliations

Soon will be listed here.

Abstract

Spermatogenesis is the highly orchestrated process involving expression of a series of testicular genes. Testis-enriched genes are critical for cellular processes during spermatogenesis whose disruption leads to impaired spermatogenesis and male infertility. Nevertheless, among poorly investigated testicular genes are the mouse and human which were identified in the current study as novel testis-enriched genes through transcriptomic analyses. In particular, as orthologous alternative splicing isoforms, mouse E-form and human C-form containing the SAM domain were specific to testes. Western blot analyses revealed that the murine E-form was predominantly found in the testis. Analyses on GEO2R and single-cell RNA-seq datasets revealed that the / expression was enriched in spermatids among various types of cells in adult testes. To investigate functions of , knockout mice were generated using the CRISPR/Cas9 system. The deficiency resulted in lower testis weight, absence of elongated spermatids, and an increased number of apoptotic cells. Profiling of gene expression in human testis samples revealed that the expression was comparable between obstructive azoospermia patients and normal controls, but significantly lowered in nonobstructive azoospermia (NOA) patients. Among three subgroups of NOA, pre-meiotic arrest (NOA-pre), meiotic arrest (NOA-mei), and post-meiotic arrest (NOA-post), expression level of was higher in the NOA-post than the NOA-mei, but there was no difference between the NOA-pre and NOA-mei. The current studies demonstrated spermatid stage-specific expression of /, and impairment of the late stages of spermatogenesis by disruption of the mouse gene. These data suggest that / plays an essential role in normal spermatogenesis, and SAMD4A, as a spermatid specific marker, can be used for subcategorizing NOA patients. Further understanding the molecular role of SAMD4A will advance our knowledge on genetic regulations in male infertility.

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