{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:23:39Z","timestamp":1784823819486,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31501200, 31871179 and 32071161"],"award-info":[{"award-number":["31501200, 31871179 and 32071161"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Maturing male germ cells undergo a unique developmental process in spermiogenesis that replaces nucleosomal histones with protamines, the process of which is critical for testicular development and male fertility. The progress of this exchange is regulated by complex mechanisms that are not well understood. Now, with mouse genetic models, we show that barrier-to-autointegration factor-like protein (BAF-L) plays an important role in spermiogenesis and spermatozoal function. BAF-L is a male germ cell marker, whose expression is highly associated with the maturation of male germ cells. The genetic deletion of BAF-L in mice impairs the progress of spermiogenesis and thus male fertility. This effect on male fertility is a consequence of the disturbed homeostasis of histones and protamines in maturing male germ cells, in which the interactions between BAF-L and histones\/protamines are implicated. Finally, we show that reduced testicular expression of BAF-L represents a risk factor of human male infertility.<\/jats:p>","DOI":"10.3390\/ijms23041985","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T05:14:43Z","timestamp":1644556483000},"page":"1985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["BAF-L Modulates Histone-to-Protamine Transition during Spermiogenesis"],"prefix":"10.3390","volume":"23","author":[{"given":"Chao","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Gong","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Mu","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinting","family":"Lan","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, 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J. Anat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fertnstert.2009.10.045","article-title":"The genetic causes of male factor infertility: A review","volume":"93","author":"Varghese","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R988","DOI":"10.1016\/j.cub.2017.07.067","article-title":"Spermatogenesis","volume":"27","author":"Nishimura","year":"2017","journal-title":"Curr. Biol. CB"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e979623","DOI":"10.4161\/21565562.2014.979623","article-title":"Mechanisms of spermiogenesis and spermiation and how they are disturbed","volume":"4","year":"2014","journal-title":"Spermatogenesis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bbagrm.2013.08.004","article-title":"Chromatin dynamics during spermiogenesis","volume":"1839","author":"Rathke","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1111\/j.1432-1033.2004.04266.x","article-title":"The role of histones in chromatin remodelling during mammalian spermiogenesis","volume":"271","author":"Govin","year":"2004","journal-title":"Eur. J. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1530\/REP-15-0562","article-title":"Epigenetic regulation of the histone-to-protamine transition during spermiogenesis","volume":"151","author":"Bao","year":"2016","journal-title":"Reproduction"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.tcb.2007.02.004","article-title":"Barrier-to-autointegration factor\u2014A BAFfling little protein","volume":"17","author":"Margalit","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1083\/jcb.201901116","article-title":"Repair of nuclear ruptures requires barrier-to-autointegration factor","volume":"218","author":"Halfmann","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ceb.2015.05.006","article-title":"Barrier to Autointegration Factor (BANF1): Interwoven roles in nuclear structure, genome integrity, innate immunity, stress responses and progeria","volume":"34","author":"Jamin","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5501","DOI":"10.1038\/s41467-019-13167-5","article-title":"Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage","volume":"10","author":"Bolderson","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1083\/jcb.200202019","article-title":"Barrier-to-autointegration factor: Major roles in chromatin decondensation and nuclear assembly","volume":"158","author":"Kowalski","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.yexcr.2005.11.013","article-title":"Barrier-to-autointegration factor-like (BAF-L): A proposed regulator of BAF","volume":"312","author":"Tifft","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1530\/REP-17-0358","article-title":"LEM-domain proteins are lost during human spermiogenesis but BAF and BAF-L persist","volume":"154","author":"Elkhatib","year":"2017","journal-title":"Reproduction"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/mrd.20010","article-title":"Expression profiling of the developing testis in wild-type and Dazl knockout mice","volume":"67","author":"Maratou","year":"2004","journal-title":"Mol. Reprod. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.rbmo.2017.07.013","article-title":"Abnormal retention of nuclear lamina and disorganization of chromatin-related proteins in spermatozoa from DPY19L2-deleted globozoospermic patients","volume":"35","author":"Paci","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00013.2015","article-title":"Spermatogenesis: The commitment to meiosis","volume":"96","author":"Griswold","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/s41467-019-09182-1","article-title":"Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis","volume":"10","author":"Ernst","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1242\/jcs.00682","article-title":"Barrier-to-autointegration factor plays crucial roles in cell cycle progression and nuclear organization in Drosophila","volume":"116","author":"Furukawa","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_20","first-page":"1363","article-title":"Regulation of spermatogenesis","volume":"1","author":"Sharpe","year":"1994","journal-title":"Physiol. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev.cellbio.24.110707.175355","article-title":"Regulation of spermatogonial stem cell self-renewal in mammals","volume":"24","author":"Oatley","year":"2008","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nsmb.3206","article-title":"Mammalian elongation factor 4 regulates mitochondrial translation essential for spermatogenesis","volume":"23","author":"Gao","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1038\/ncomms4812","article-title":"Chd5 orchestrates chromatin remodelling during sperm development","volume":"5","author":"Li","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/j.1365-2605.1990.tb01052.x","article-title":"Aniline blue staining as a marker of sperm chromatin defects associated with different semen characteristics discriminates between proven fertile and suspected infertile men","volume":"13","author":"Auger","year":"1990","journal-title":"Int. J. Androl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.devcel.2010.01.010","article-title":"RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis","volume":"18","author":"Lu","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21776","DOI":"10.1038\/srep21776","article-title":"Knockout of BRD7 results in impaired spermatogenesis and male infertility","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107950","DOI":"10.1016\/j.celrep.2020.107950","article-title":"PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis","volume":"32","author":"Kim","year":"2020","journal-title":"Cell Rep."},{"key":"ref_28","unstructured":"World-Health-Organization (2010). WHO Laboratory Manual for the Examination and Processing of Human Semen, WHO."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ydbio.2008.05.553","article-title":"Nuclear regulator Pygo2 controls spermiogenesis and histone H3 acetylation","volume":"320","author":"Nair","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature06236","article-title":"Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis","volume":"450","author":"Okada","year":"2007","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000513850","article-title":"Mus musculus Barrier-To-Autointegration Factor 2 (Banf2) is Not Essential for Spermatogenesis or Fertility","volume":"161","author":"Niu","year":"2021","journal-title":"Cytogenet. Genome Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43288","DOI":"10.1074\/jbc.M207952200","article-title":"Barrier to autointegration factor interacts with the cone-rod homeobox and represses its transactivation function","volume":"277","author":"Wang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature13992","article-title":"A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"962","DOI":"10.3389\/fgene.2019.00962","article-title":"Essential Role of Histone Replacement and Modifications in Male Fertility","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/38664","article-title":"Histone acetylation in chromatin structure and transcription","volume":"389","author":"Grunstein","year":"1997","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e00082-17","DOI":"10.1128\/MCB.00082-17","article-title":"EPC1\/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice","volume":"37","author":"Dong","year":"2017","journal-title":"Mol. Cell. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/01485010390219656","article-title":"Asthenozoospermia: Analysis of a large population","volume":"49","author":"Curi","year":"2003","journal-title":"Arch. Androl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e13463","DOI":"10.1111\/and.13463","article-title":"Asthenozoospermia: Cellular and molecular contributing factors and treatment strategies","volume":"52","author":"Shahrokhi","year":"2020","journal-title":"Andrologia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1093\/humrep\/dem069","article-title":"A role for tachykinins in the regulation of human sperm motility","volume":"22","author":"Ravina","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41684-020-00692-w","article-title":"Replacement of surgical vasectomy through the use of wild-type sterile hybrids","volume":"50","author":"Preece","year":"2021","journal-title":"Lab Anim."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"pdb.prot5439","DOI":"10.1101\/pdb.prot5439","article-title":"Purification of RNA using TRIzol (TRI reagent)","volume":"2010","author":"Rio","year":"2010","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4103\/1947-2714.128482","article-title":"Western blot: Technique, theory and trouble shooting","volume":"6","author":"Liu","year":"2014","journal-title":"N. Am. J. Med. Sci."},{"key":"ref_43","unstructured":"Biggers, J., Whitten, W., and Whittingham, D. (1971). The culture of mouse embryos in vitro. Fac. Res. 1970\u20131979, 193. Available online: https:\/\/mouseion.jax.org\/stfb1970_1979\/193."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"pdb.prot098640","DOI":"10.1101\/pdb.prot098640","article-title":"Immunoprecipitation","volume":"2017","author":"DeCaprio","year":"2017","journal-title":"Cold Spring Harb. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/1985\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:18:09Z","timestamp":1760134689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/1985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23041985"],"URL":"https:\/\/doi.org\/10.3390\/ijms23041985","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]}}}