{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that mutations in M1AP, a gene critical for male germ cell development, lead to severe spermatogenic failure and non‐obstructive azoospermia. In affected men, homozygous frameshift and missense variants in M1AP compromise protein function, causing an arrest during meiosis that culminates in meiotic failure and, in certain cases, the occasional presence of spermatids or rare spermatozoa in the ejaculate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn murine models, M1ap is expressed in germ cells from spermatogonia through secondary spermatocytes, and its ablation results in reduced testicular size and multiple tubular defects. Specifically, M1ap‐deficient males exhibit spermatogenic arrest at both the zygotene/pachytene and metaphase I stages—reflecting an impaired ability to achieve proper chromosome alignment, synapsis, and crossover formation—which underscores its indispensable role in orchestrating meiotic progression during spermatogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, expression studies on D6Mm5e have identified an evolutionarily conserved gene with a highly restricted gonadal expression profile. D6Mm5e is active in female germ cells at the onset of meiosis and in male germ cells during the terminal stages of spermatogenesis, suggesting that it may participate in the regulation of gametogenesis alongside genes such as M1AP."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Margot J Wyrwoll, Şehime G Temel, Liina Nagirnaja, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severely Impaired Spermatogenesis Leading to Male Infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2020.06.010"}], "href": "https://doi.org/10.1016/j.ajhg.2020.06.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32673564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32673564"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nelson Alexander Arango, Li Li, Deepa Dabir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meiosis I arrest abnormalities lead to severe oligozoospermia in meiosis 1 arresting protein (M1ap)-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.111.098673"}], "href": "https://doi.org/10.1095/biolreprod.111.098673"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23269666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23269666"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nelson A Arango, Tiffany T Huang, Akihiro Fujino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression analysis and evolutionary conservation of the mouse germ cell-specific D6Mm5e gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.20907"}], "href": "https://doi.org/10.1002/dvdy.20907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16881047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16881047"}]}]}]}