{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:49:15Z","timestamp":1778856555048,"version":"3.51.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003627","name":"Rural Development Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>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 <jats:italic>Samd4a<\/jats:italic> and human <jats:italic>SAMD4A<\/jats:italic> which were identified in the current study as novel testis-enriched genes through transcriptomic analyses. In particular, as orthologous alternative splicing isoforms, mouse <jats:italic>Samd4a<\/jats:italic> E-form and human <jats:italic>SAMD4A<\/jats:italic>C-form containing the SAM domain were specific to testes. Western blot analyses revealed that the murine <jats:italic>SAMD4A<\/jats:italic>E-form was predominantly found in the testis. Analyses on GEO2R and single-cell RNA-seq datasets revealed that the <jats:italic>Samd4a<\/jats:italic>\/<jats:italic>SAMD4A<\/jats:italic> expression was enriched in spermatids among various types of cells in adult testes. To investigate <jats:italic>in vivo<\/jats:italic> functions of <jats:italic>Samd4a<\/jats:italic>, <jats:italic>Samd4a<\/jats:italic> knockout mice were generated using the CRISPR\/Cas9 system. The <jats:italic>Samd4a<\/jats:italic> 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 <jats:italic>SAMD4A<\/jats:italic> 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 <jats:italic>SAMD4A<\/jats:italic> 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 <jats:italic>Samd4a<\/jats:italic>\/<jats:italic>SAMD4A<\/jats:italic>, and impairment of the late stages of spermatogenesis by disruption of the mouse <jats:italic>Samd4a<\/jats:italic> gene. These data suggest that <jats:italic>Samd4a<\/jats:italic>\/<jats:italic>SAMD4A<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/fcell.2022.978343","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T05:11:11Z","timestamp":1664946671000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["A novel testis-enriched gene, Samd4a, regulates spermatogenesis as a spermatid-specific factor"],"prefix":"10.3389","volume":"10","author":[{"given":"Jinsoo","family":"Ahn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Ryung","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeunsu","family":"Suh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haesun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seongsoo","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lovelia L.","family":"Mamuad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Suk","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kichoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.3390\/ani11051315","article-title":"Genomic imprinting at the porcine DIRAS3 locus","volume":"11","author":"Ahn","year":"2021","journal-title":"Animals."},{"key":"B2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.gene.2018.05.101","article-title":"Adipose-specific expression of mouse Rbp7 gene and its developmental and metabolic changes","volume":"670","author":"Ahn","year":"2018","journal-title":"Gene"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0175787","DOI":"10.1371\/journal.pone.0175787","article-title":"Comparative expression profiling of testis-enriched genes regulated during the development of spermatogonial cells","volume":"12","author":"Ahn","year":"2017","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3087","DOI":"10.1038\/s41598-019-39582-8","article-title":"Integrative analysis revealing human adipose-specific genes and consolidating obesity loci","volume":"9","author":"Ahn","year":"2019","journal-title":"Sci. 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