{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:48:22Z","timestamp":1777495702596,"version":"3.51.4"},"reference-count":45,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201834"],"award-info":[{"award-number":["82201834"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2208085QH233"],"award-info":[{"award-number":["2208085QH233"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","award":["2019PT310002"],"award-info":[{"award-number":["2019PT310002"]}],"id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2700901"],"award-info":[{"award-number":["2021YFC2700901"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["2021xkjT030"],"award-info":[{"award-number":["2021xkjT030"]}],"id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","rbmojournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Reproductive BioMedicine Online"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.rbmo.2025.104974","type":"journal-article","created":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T17:02:09Z","timestamp":1742662929000},"page":"104974","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel homozygous variants in piRNA pathway factors lead to male infertility in humans"],"prefix":"10.1016","volume":"51","author":[{"given":"Kaiqin","family":"Hu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Sha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenwan","family":"Zu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanxiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiru","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuokuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjuan","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxia","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9799-814X","authenticated-orcid":false,"given":"Rui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.rbmo.2025.104974_bib0001","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0002","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod Biol Endocrinol"},{"key":"10.1016\/j.rbmo.2025.104974_bib0003","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1136\/jmedgenet-2017-104514","article-title":"Mutation in TDRD9 causes non-obstructive azoospermia in infertile men","volume":"54","author":"Arafat","year":"2017","journal-title":"J Med Genet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0004","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.fertnstert.2021.12.012","article-title":"The sixth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen: ensuring quality and standardization in basic examination of human ejaculates","volume":"117","author":"Bjorndahl","year":"2022","journal-title":"Fertil Steril"},{"key":"10.1016\/j.rbmo.2025.104974_bib0005","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1745-7262.2006.00123.x","article-title":"Male idiopathic oligoasthenoteratozoospermia","volume":"8","author":"Cavallini","year":"2006","journal-title":"Asian J Androl"},{"key":"10.1016\/j.rbmo.2025.104974_bib0006","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev-genet-120417-031441","article-title":"piRNA-Guided Genome Defense: From Biogenesis to Silencing","volume":"52","author":"Czech","year":"2018","journal-title":"Annu Rev Genet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0007","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.molcel.2013.04.007","article-title":"A transcriptome-wide RNAi screen in the Drosophila ovary reveals factors of the germline piRNA pathway","volume":"50","author":"Czech","year":"2013","journal-title":"Mol Cell"},{"key":"10.1016\/j.rbmo.2025.104974_bib0008","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s11427-020-1632-5","article-title":"A dual role of the PIWI\/piRNA machinery in regulating mRNAs during mouse spermiogenesis","volume":"63","author":"Dai","year":"2020","journal-title":"Sci China Life Sci"},{"key":"10.1016\/j.rbmo.2025.104974_bib0009","doi-asserted-by":"crossref","DOI":"10.1016\/j.fertnstert.2013.12.054","article-title":"Array-based DNA methylation profiling in male infertility reveals allele-specific DNA methylation in PIWIL1 and PIWIL2","volume":"101","author":"Friemel","year":"2014","journal-title":"Fertil Steril"},{"key":"10.1016\/j.rbmo.2025.104974_bib0010","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature04917","article-title":"A germline-specific class of small RNAs binds mammalian Piwi proteins","volume":"442","author":"Girard","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.rbmo.2025.104974_bib0011","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2017.04.034","article-title":"Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis","volume":"169","author":"Gou","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.rbmo.2025.104974_bib0012","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1093\/humrep\/deq274","article-title":"Genetic variants in Piwi-interacting RNA pathway genes confer susceptibility to spermatogenic failure in a Chinese population","volume":"25","author":"Gu","year":"2010","journal-title":"Hum Reprod"},{"key":"10.1016\/j.rbmo.2025.104974_bib0013","first-page":"1270","article-title":"Homozygous deleterious variants in the C-terminal of TDRD5 impair spermiogenesis, causing severe oligoasthenoteratozoospermia in humans","volume":"5","author":"Guo","year":"2024","journal-title":"Andrology"},{"key":"10.1016\/j.rbmo.2025.104974_bib0014","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1136\/jmg-2023-109766","article-title":"Bi-allelic variants in chromatoid body protein TDRD6 cause spermiogenesis defects and severe oligoasthenoteratozoospermia in humans","volume":"61","author":"Guo","year":"2024","journal-title":"J Med Genet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0015","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.molcel.2013.04.031","article-title":"The genetic makeup of the Drosophila piRNA pathway","volume":"50","author":"Handler","year":"2013","journal-title":"Mol Cell"},{"key":"10.1016\/j.rbmo.2025.104974_bib0016","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1530\/REP-16-0586","article-title":"Expression patterns of HENMT1 and PIWIL1 in human testis: implications for transposon expression","volume":"154","author":"Hempfling","year":"2017","journal-title":"Reproduction"},{"key":"10.1016\/j.rbmo.2025.104974_bib0017","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.cub.2007.06.030","article-title":"The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC","volume":"17","author":"Horwich","year":"2007","journal-title":"Curr Biol"},{"key":"10.1016\/j.rbmo.2025.104974_bib0018","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1093\/humupd\/dmaa034","article-title":"Molecular genetics of infertility: loss-of-function mutations in humans and corresponding knockout\/mutated mice","volume":"27","author":"Jiao","year":"2021","journal-title":"Hum Reprod Update"},{"key":"10.1016\/j.rbmo.2025.104974_bib0019","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1038\/emboj.2010.233","article-title":"Hen1 is required for oocyte development and piRNA stability in zebrafish","volume":"29","author":"Kamminga","year":"2010","journal-title":"EMBO J"},{"key":"10.1016\/j.rbmo.2025.104974_bib0020","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ajhg.2022.01.011","article-title":"Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia","volume":"109","author":"Kherraf","year":"2022","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0021","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"Kumar","year":"2009","journal-title":"Nat Protoc"},{"key":"10.1016\/j.rbmo.2025.104974_bib0022","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1095\/biolreprod.109.076000","article-title":"Identification of potentially damaging amino acid substitutions leading to human male infertility","volume":"81","author":"Kuzmin","year":"2009","journal-title":"Biol Reprod"},{"key":"10.1016\/j.rbmo.2025.104974_bib0023","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.rbmo.2025.104974_bib0024","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.rbmo.2025.104974_bib0025","doi-asserted-by":"crossref","first-page":"D1039","DOI":"10.1093\/nar\/gkx1039","article-title":"VarCards: an integrated genetic and clinical database for coding variants in the human genome","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.rbmo.2025.104974_bib0026","first-page":"1675","article-title":"Defective piRNA Processing and Azoospermia","volume":"386","author":"Li","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.rbmo.2025.104974_bib0027","article-title":"HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse","volume":"11","author":"Lim","year":"2015","journal-title":"PLoS Genet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0028","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007590","article-title":"The methyltransferase HEN1 is required in Nematostella vectensis for microRNA and piRNA stability as well as larval metamorphosis","volume":"14","author":"Modepalli","year":"2018","journal-title":"PLoS Genet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0029","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1056\/NEJMoa2028973","article-title":"Variant PNLDC1, Defective piRNA Processing, and Azoospermia","volume":"385","author":"Nagirnaja","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1016\/j.rbmo.2025.104974_bib0030","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1038\/emboj.2009.365","article-title":"Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines","volume":"28","author":"Nishida","year":"2009","journal-title":"EMBO J"},{"key":"10.1016\/j.rbmo.2025.104974_bib0031","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/andr.13361","article-title":"Intermitochondrial cement (IMC) harbors piRNA biogenesis machinery and exonuclease domain-containing proteins EXD1 and EXD2 in mouse spermatocytes","volume":"11","author":"Olotu","year":"2023","journal-title":"Andrology"},{"key":"10.1016\/j.rbmo.2025.104974_bib0032","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41576-018-0073-3","article-title":"PIWI-interacting RNAs: small RNAs with big functions","volume":"20","author":"Ozata","year":"2019","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.rbmo.2025.104974_bib0033","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2018.08.087","article-title":"Exonuclease Domain-Containing 1 Enhances MIWI2 piRNA Biogenesis via Its Interaction with TDRD12","volume":"24","author":"Pandey","year":"2018","journal-title":"Cell Rep"},{"key":"10.1016\/j.rbmo.2025.104974_bib0034","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.fertnstert.2018.09.012","article-title":"Management of nonobstructive azoospermia: a committee opinion","volume":"110","year":"2018","journal-title":"Fertil Steril"},{"key":"10.1016\/j.rbmo.2025.104974_bib0035","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1101\/gad.1563607","article-title":"Pimet, the Drosophila homolog of HEN1, mediates 2\u2032-O-methylation of Piwi- interacting RNAs at their 3\u2032 ends","volume":"21","author":"Saito","year":"2007","journal-title":"Genes Dev"},{"key":"10.1016\/j.rbmo.2025.104974_bib0036","first-page":"121","article-title":"PIWI, piRNAs, and germline stem cells: what's the link?","volume":"82","author":"Samji","year":"2009","journal-title":"Yale J Biol Med"},{"key":"10.1016\/j.rbmo.2025.104974_bib0037","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat Methods"},{"key":"10.1016\/j.rbmo.2025.104974_bib0038","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.devcel.2009.10.012","article-title":"The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline","volume":"17","author":"Shoji","year":"2009","journal-title":"Dev Cell"},{"key":"10.1016\/j.rbmo.2025.104974_bib0039","doi-asserted-by":"crossref","first-page":"6637","DOI":"10.1038\/s41467-024-50930-9","article-title":"Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility","volume":"15","author":"Stallmeyer","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.rbmo.2025.104974_bib0040","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.cellbio.24.110707.175327","article-title":"The biogenesis and function of PIWI proteins and piRNAs: progress and prospect","volume":"25","author":"Thomson","year":"2009","journal-title":"Annu Rev Cell Dev Biol"},{"key":"10.1016\/j.rbmo.2025.104974_bib0041","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel concepts in the aetiology of male reproductive impairment","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.rbmo.2025.104974_bib0042","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.rbmo.2025.104974_bib0043","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.molcel.2015.11.009","article-title":"PIWI Slicing and EXD1 Drive Biogenesis of Nuclear piRNAs from Cytosolic Targets of the Mouse piRNA Pathway","volume":"61","author":"Yang","year":"2016","journal-title":"Mol Cell"},{"key":"10.1016\/j.rbmo.2025.104974_bib0044","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1093\/humrep\/dex234","article-title":"The International Glossary on Infertility and Fertility Care, 2017","volume":"32","author":"Zegers-Hochschild","year":"2017","journal-title":"Hum Reprod"},{"key":"10.1016\/j.rbmo.2025.104974_bib0045","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4103\/aja20233","article-title":"A novel loss-of-function variant in PNLDC1 inducing oligo-astheno-teratozoospermia and male infertility","volume":"25","author":"Zhao","year":"2023","journal-title":"Asian J Androl"}],"container-title":["Reproductive BioMedicine Online"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1472648325001816?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1472648325001816?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T20:23:35Z","timestamp":1762547015000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1472648325001816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S1472648325001816"],"URL":"https:\/\/doi.org\/10.1016\/j.rbmo.2025.104974","relation":{},"ISSN":["1472-6483"],"issn-type":[{"value":"1472-6483","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel homozygous variants in piRNA pathway factors lead to male infertility in humans","name":"articletitle","label":"Article Title"},{"value":"Reproductive BioMedicine Online","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.rbmo.2025.104974","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"104974"}}