{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:54:21Z","timestamp":1790819661481,"version":"4.1.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China","award":["JYB2025XDXM503"],"award-info":[{"award-number":["JYB2025XDXM503"]}],"id":[{"id":"https:\/\/ror.org\/03m01yf64","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32288102"],"award-info":[{"award-number":["32288102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Cornerstone Science Foundation","award":["NCI202308"],"award-info":[{"award-number":["NCI202308"]}]},{"name":"Peking-Tsinghua Center for Life Sciences","id":[{"id":"https:\/\/ror.org\/05kje8j93","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spermatogenesis is an intricately regulated epigenetic process, yet the exact chromatin dynamics during human meiosis and their systemic failure in non-obstructive azoospermia remain elusive due to the sparsity of single-cell epigenomic data in previous studies. Here, leveraging a high-quality scATAC-seq approach, we mapped over 810,000 cis-regulatory elements across human spermatogenesis. We uncovered a highly synchronized, wave-like activation of master transcription factor networks that precisely orchestrates meiotic progression. Crucially, we traced the dynamic process of opening and closing of chromatin states at meiotic DNA double-strand break hotspot regions at single-cell resolution, defining a transient epigenetic window where thousands of these predefined regions become specifically accessible. In NOA patients, this delicate architecture collapses, leading to severe spermatogenic arrest predominantly at the zygotene stage. We characterize this pathogenesis as the temporal dephasing and decoupling of the activities of master TFs. Furthermore, aberrantly reduced chromatin accessibility at DSB hotspot regions in NOA is potentially associated with defective DSB formation, accompanied by a two- to three-fold increase in sperm aneuploidy. Finally, we establish a functional paradigm for interpreting male infertility by linking non-coding GWAS variants (e.g., the MHC II locus) and rare point mutations to the disruption of cis-regulatory elements. Together, our findings establish a high-resolution epigenetic framework for human spermatogenesis and provide a mechanistic basis for decoding the etiology and heterogeneity of non-obstructive azoospermia.<\/jats:p>","DOI":"10.1093\/procel\/pwag033","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:32:09Z","timestamp":1779190329000},"page":"934-953","source":"Crossref","is-referenced-by-count":1,"title":["Epigenetic dynamics of human spermatogenesis and their dysregulation in non-obstructive azoospermia"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0001-0631","authenticated-orcid":false,"given":"Haoling","family":"Xie","sequence":"first","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]},{"name":"Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University , Beijing 100875,","place":["China"]},{"name":"Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation , Beijing 100871,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-5005","authenticated-orcid":false,"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]},{"name":"Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation , Beijing 100871,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6669-4698","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education , Beijing 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8240-3521","authenticated-orcid":false,"given":"Xueqiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]},{"name":"Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation , Beijing 100871,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-5431","authenticated-orcid":false,"given":"Zhenhuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]},{"name":"Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation , Beijing 100871,","place":["China"]},{"name":"Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youran","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University , Beijing 100875,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-1876","authenticated-orcid":false,"given":"Lu","family":"Wen","sequence":"additional","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation , Beijing 100871,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2126-1376","authenticated-orcid":false,"given":"Jie","family":"Qiao","sequence":"additional","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education , Beijing 100191,","place":["China"]},{"name":"Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]},{"name":"Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation , Beijing 100871,","place":["China"]},{"name":"Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-7717","authenticated-orcid":false,"given":"Fuchou","family":"Tang","sequence":"additional","affiliation":[{"name":"Biomedical Pioneering Innovation Center, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing 100191,","place":["China"]},{"name":"Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]},{"name":"Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation , Beijing 100871,","place":["China"]},{"name":"Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"2026093020541994900_pwag033-B1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/s41586-020-2493-4","article-title":"Expanded encyclopaedias of DNA elements in the human and mouse genomes","volume":"583","author":"Abascal","year":"2020","journal-title":"Nature"},{"key":"2026093020541994900_pwag033-B2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev-genom-110122-090239","article-title":"Meiotic chromosome structure, the synaptonemal complex, and infertility","volume":"24","author":"Adams","year":"2023","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2026093020541994900_pwag033-B3","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: Single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat Methods"},{"key":"2026093020541994900_pwag033-B4","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nrg3573","article-title":"Meiotic recombination in mammals: Localization and regulation","volume":"14","author":"Baudat","year":"2013","journal-title":"Nat Rev Genet"},{"key":"2026093020541994900_pwag033-B5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41586-020-2347-0","article-title":"Insights into variation in meiosis from 31,228 human sperm genomes","volume":"583","author":"Bell","year":"2020","journal-title":"Nature"},{"key":"2026093020541994900_pwag033-B6","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.cub.2019.02.007","article-title":"Prdm9 and meiotic cohesin proteins cooperatively promote DNA double-strand break formation in mammalian spermatocytes","volume":"29","author":"Bhattacharyya","year":"2019","journal-title":"Curr Biol"},{"key":"2026093020541994900_pwag033-B7","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/s41592-023-01938-4","article-title":"SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks","volume":"20","author":"Bravo Gonz\u00e1lez-Blas","year":"2023","journal-title":"Nat Methods"},{"key":"2026093020541994900_pwag033-B8","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/s42003-022-04192-0","article-title":"Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility","volume":"5","author":"Cerv\u00e1n-Mart\u00edn","year":"2022","journal-title":"Commun Biol"},{"key":"2026093020541994900_pwag033-B9","doi-asserted-by":"crossref","first-page":"e2206852","DOI":"10.1002\/advs.202206852","article-title":"Deciphering the molecular characteristics of human idiopathic nonobstructive azoospermia from the perspective of germ cells","volume":"10","author":"Chen","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"2026093020541994900_pwag033-B10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41422-020-0281-1","article-title":"Refined spatial temporal epigenomic profiling reveals intrinsic connection between PRDM9-mediated H3K4me3 and the fate of double-stranded breaks","volume":"30","author":"Chen","year":"2020","journal-title":"Cell Res"},{"key":"2026093020541994900_pwag033-B11","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/s41422-018-0074-y","article-title":"Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis","volume":"28","author":"Chen","year":"2018","journal-title":"Cell Res"},{"key":"2026093020541994900_pwag033-B12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/aja.2012.141","article-title":"Microdissection testicular sperm extraction: an update","volume":"15","author":"Dabaja","year":"2013","journal-title":"Asian J Androl"},{"key":"2026093020541994900_pwag033-B13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12915-022-01318-y","article-title":"Asynchronous embryonic germ cell development leads to a heterogeneity of postnatal ovarian follicle activation and may influence the timing of puberty onset in mice","volume":"20","author":"Dai","year":"2022","journal-title":"BMC Biol"},{"key":"2026093020541994900_pwag033-B14","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.15252\/embr.201744059","article-title":"Transposon-driven transcription is a conserved feature of vertebrate spermatogenesis and transcript evolution","volume":"18","author":"Davis","year":"2017","journal-title":"EMBO Rep"},{"key":"2026093020541994900_pwag033-B15","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1101\/gad.329705","article-title":"Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation","volume":"19","author":"De Vries","year":"2005","journal-title":"Genes Dev"},{"key":"2026093020541994900_pwag033-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humrep\/deac245","article-title":"Human spermatogonial stem cells and their niche in male (in)fertility: Novel concepts from single-cell RNA-sequencing","volume":"38","author":"Di Persio","year":"2023","journal-title":"Hum Reprod"},{"key":"2026093020541994900_pwag033-B17","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1093\/hmg\/ddm246","article-title":"Abnormal meiotic recombination in infertile men and its association with sperm aneuploidy","volume":"16","author":"Ferguson","year":"2007","journal-title":"Hum Mol Genet"},{"key":"2026093020541994900_pwag033-B18","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41586-022-05279-8","article-title":"Inferring and perturbing cell fate regulomes in human brain organoids","volume":"621","author":"Fleck","year":"2023","journal-title":"Nature"},{"key":"2026093020541994900_pwag033-B19","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.cell.2013.10.001","article-title":"A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes","volume":"155","author":"Flemr","year":"2013","journal-title":"Cell"},{"key":"2026093020541994900_pwag033-B20","doi-asserted-by":"crossref","first-page":"13298","DOI":"10.1038\/ncomms13298","article-title":"C14ORF39\/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility","volume":"7","author":"G\u00f3mez-H","year":"2016","journal-title":"Nat Commun"},{"key":"2026093020541994900_pwag033-B21","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41588-021-00790-6","article-title":"Author correction: ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis","volume":"53","author":"Granja","year":"2021","journal-title":"Nat Genet"},{"key":"2026093020541994900_pwag033-B22","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41422-018-0099-2","article-title":"The adult human testis transcriptional cell atlas","volume":"28","author":"Guo","year":"2018","journal-title":"Cell Res"},{"key":"2026093020541994900_pwag033-B23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.6061\/clinics\/2013(Sup01)06","article-title":"A comprehensive review of genetics and genetic testing in azoospermia","volume":"68","author":"Hamada","year":"2013","journal-title":"Clinics (Sao Paulo)"},{"key":"2026093020541994900_pwag033-B24","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/nrg2723","article-title":"Genetics of mammalian meiosis: regulation, dynamics and impact on fertility","volume":"11","author":"Handel","year":"2010","journal-title":"Nat Rev Genet"},{"key":"2026093020541994900_pwag033-B25","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1038\/ncomms4857","article-title":"Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men","volume":"5","author":"Hu","year":"2014","journal-title":"Nat Commun"},{"key":"2026093020541994900_pwag033-B26","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ng.1040","article-title":"A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia","volume":"44","author":"Hu","year":"2011","journal-title":"Nat Genet"},{"key":"2026093020541994900_pwag033-B27","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1038\/s41556-023-01232-7","article-title":"Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination","volume":"25","author":"Huang","year":"2023","journal-title":"Nat Cell Biol"},{"key":"2026093020541994900_pwag033-B28","article-title":"Meiotic recombination: the essence of heredity","volume":"7","author":"Hunter","year":"2015","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2026093020541994900_pwag033-B29","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/gtc.12652","article-title":"The cohesin complex in mammalian meiosis","volume":"24","author":"Ishiguro","year":"2019","journal-title":"Genes Cells"},{"key":"2026093020541994900_pwag033-B30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1755-8166-6-1","article-title":"A specific family of interspersed repeats (SINEs) facilitates meiotic synapsis in mammals","volume":"6","author":"Johnson","year":"2013","journal-title":"Mol Cytogenet"},{"key":"2026093020541994900_pwag033-B31","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/s41588-018-0047-6","article-title":"Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases","volume":"50","author":"Kanai","year":"2018","journal-title":"Nat Genet"},{"key":"2026093020541994900_pwag033-B32","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1038\/s41467-019-11820-7","article-title":"Cell-type-specific genomics reveals histone modification dynamics in mammalian meiosis","volume":"10","author":"Lam","year":"2019","journal-title":"Nat Commun"},{"key":"2026093020541994900_pwag033-B33","doi-asserted-by":"crossref","first-page":"831620","DOI":"10.3389\/fgene.2022.831620","article-title":"Meiotic genes and DNA double strand break repair in cancer","volume":"13","author":"Lingg","year":"2022","journal-title":"Front Genet"},{"key":"2026093020541994900_pwag033-B34","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1158\/2159-8290.CD-23-1445","article-title":"Single-cell chromatin accessibility analysis reveals the epigenetic basis and signature transcription factors for the molecular subtypes of colorectal cancers","volume":"14","author":"Liu","year":"2024","journal-title":"Cancer Discov"},{"key":"2026093020541994900_pwag033-B35","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1126\/science.1229112","article-title":"Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing","volume":"338","author":"Lu","year":"2012","journal-title":"Science"},{"key":"2026093020541994900_pwag033-B36","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-024-08104-6","volume-title":"How the Extra X Chromosome Impairs the Development of Male Fetal Germ Cells","author":"Lu","year":"2024"},{"key":"2026093020541994900_pwag033-B37","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1021\/acs.biochem.5b01126","article-title":"Relaxed chromatin formation and weak suppression of homologous pairing by the testis-specific linker histone H1T","volume":"55","author":"MacHida","year":"2016","journal-title":"Biochemistry"},{"key":"2026093020541994900_pwag033-B38","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.ajhg.2021.09.001","article-title":"Comparative single-cell analysis of biopsies clarifies pathogenic mechanisms in Klinefelter syndrome","volume":"108","author":"Mahyari","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2026093020541994900_pwag033-B39","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4161\/cc.9.1.10348","article-title":"The multiple roles of Bub1 in chromosome segregation during mitosis and meiosis","volume":"9","author":"Marchetti","year":"2010","journal-title":"Cell Cycle"},{"key":"2026093020541994900_pwag033-B40","doi-asserted-by":"crossref","first-page":"7986","DOI":"10.1093\/nar\/gkab621","article-title":"Discovering single nucleotide variants and indels from bulk and single-cell ATAC-seq","volume":"49","author":"Massarat","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2026093020541994900_pwag033-B41","doi-asserted-by":"crossref","first-page":"R107","DOI":"10.1530\/REP-12-0497","article-title":"Human testicular peritubular cells: more than meets the eye","volume":"145","author":"Mayerhofer","year":"2013","journal-title":"Reproduction"},{"key":"2026093020541994900_pwag033-B42","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.dnarep.2018.09.003","article-title":"Regulation of the initiation of DNA replication in human cells","volume":"72","author":"Moiseeva","year":"2018","journal-title":"DNA Repair (Amst)"},{"key":"2026093020541994900_pwag033-B43","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/ng.213","article-title":"A common sequence motif associated with recombination hot spots and genome instability in humans","volume":"40","author":"Myers","year":"2008","journal-title":"Nat Genet"},{"key":"2026093020541994900_pwag033-B44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1159\/000325218","article-title":"Expression of PITX2 homeodomain transcription factor during rat gonadal development in a sexually dimorphic manner","volume":"27","author":"Nandi","year":"2011","journal-title":"Cell Physiol Biochem"},{"key":"2026093020541994900_pwag033-B45","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: Predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2026093020541994900_pwag033-B46","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1080\/15384101.2023.2171544","article-title":"Genetic variants underlying spermatogenic arrests in men with non-obstructive azoospermia","volume":"22","author":"Ozturk","year":"2023","journal-title":"Cell Cycle"},{"key":"2026093020541994900_pwag033-B47","doi-asserted-by":"crossref","first-page":"10519","DOI":"10.1093\/nar\/gkad776","article-title":"Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination","volume":"51","author":"Park","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2026093020541994900_pwag033-B48","doi-asserted-by":"crossref","first-page":"14635","DOI":"10.1073\/pnas.1516928112","article-title":"Superresolution imaging reveals structurally distinct periodic patterns of chromatin along pachytene chromosomes","volume":"112","author":"Prakash","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026093020541994900_pwag033-B49","doi-asserted-by":"crossref","first-page":"1256442","DOI":"10.1126\/science.1256442","article-title":"Recombination initiation maps\u00a0of individual human genomes","volume":"346","author":"Pratto","year":"2014","journal-title":"Science"},{"key":"2026093020541994900_pwag033-B50","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1023\/B:CHRO.0000021945.83198.0e","article-title":"Cohesin component dynamics during meiotic prophase I in mammalian oocytes","volume":"12","author":"Prieto","year":"2004","journal-title":"Chromosome Res"},{"key":"2026093020541994900_pwag033-B51","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nmeth.4401","article-title":"ChromVAR: Inferring transcription-factor-associated accessibility from single-cell epigenomic data","volume":"14","author":"Schep","year":"2017","journal-title":"Nat Methods"},{"key":"2026093020541994900_pwag033-B52","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41586-018-0237-5","article-title":"Nuclear ARP2\/3 drives DNA break clustering for homology-directed repair","volume":"559","author":"Schrank","year":"2018","journal-title":"Nature"},{"key":"2026093020541994900_pwag033-B53","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.celrep.2019.01.045","article-title":"The neonatal and adult human testis defined at the single-cell level","volume":"26","author":"Sohni","year":"2019","journal-title":"Cell Rep"},{"key":"2026093020541994900_pwag033-B54","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1134\/S1990519X1103014X","article-title":"DNA repeated sequences may be involved in synaptonemal complex formation","volume":"5","author":"Spangenberg","year":"2011","journal-title":"Cell Tiss Biol"},{"key":"2026093020541994900_pwag033-B55","doi-asserted-by":"crossref","first-page":"W322","DOI":"10.1093\/nar\/gkac393","article-title":"FABIAN-variant: predicting the effects of DNA variants on transcription factor binding","volume":"50","author":"Steinhaus","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2026093020541994900_pwag033-B56","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2026093020541994900_pwag033-B57","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/1749-4877.12663","article-title":"Pitx2 suppression at meiotic stages associates with seasonal inhibition of testis development in Rattus norvegicus caraco","volume":"18","author":"Tian","year":"2023","journal-title":"Integr Zool"},{"key":"2026093020541994900_pwag033-B58","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/nature24265","article-title":"Landscape of X chromosome inactivation across human tissues","volume":"550","author":"Tukiainen","year":"2017","journal-title":"Nature"},{"key":"2026093020541994900_pwag033-B17668121","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1242\/dev.000018","article-title":"Meiotic sex chromosome inactivation","volume":"134","author":"Turner","year":"2007","journal-title":"Development"},{"key":"2026093020541994900_pwag033-B59","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/humrep\/der077","article-title":"Disturbed spermatogenesis associated with thickened lamina propria of seminiferous tubules is not caused by dedifferentiation of myofibroblasts","volume":"26","author":"Volkmann","year":"2011","journal-title":"Hum Reprod"},{"key":"2026093020541994900_pwag033-B60","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1093\/humrep\/des115","article-title":"Testicular sperm aneuploidy in non-obstructive azoospermic patients","volume":"27","author":"Vozdova","year":"2012","journal-title":"Hum Reprod"},{"key":"2026093020541994900_pwag033-B61","doi-asserted-by":"crossref","first-page":"601","DOI":"10.24272\/j.issn.2095-8137.2023.414","article-title":"Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATACseq and scRNA-seq","volume":"45","author":"Wang","year":"2024","journal-title":"Zool Res"},{"key":"2026093020541994900_pwag033-B62","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.stem.2018.08.007","article-title":"Single-cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2026093020541994900_pwag033-B63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.97958.3","article-title":"scRNA-seq and scATAC-seq reveal that Sertoli cell mediates spermatogenesis disorders through stage-specific communications in non-obstructive azoospermia","volume":"13","author":"Wang","year":"2025","journal-title":"Elife"},{"key":"2026093020541994900_pwag033-B64","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/hmg\/ddab006","article-title":"Single-cell ATAC-Seq reveals cell type-specific transcriptional regulation and unique chromatin accessibility in human spermatogenesis","volume":"31","author":"Wu","year":"2022","journal-title":"Hum Mol Genet"},{"key":"2026093020541994900_pwag033-B65","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/humupd\/dmac024","article-title":"Meiotic recombination: insights into its mechanisms and its role in human reproduction with a special focus on non-obstructive azoospermia","volume":"28","author":"Xie","year":"2022","journal-title":"Hum Reprod Update"},{"key":"2026093020541994900_pwag033-B66","doi-asserted-by":"crossref","first-page":"8020","DOI":"10.1093\/nar\/gkad532","article-title":"Long-read-based single sperm genome sequencing for chromosome-wide haplotype phasing of both SNPs and SVs","volume":"51","author":"Xie","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2026093020541994900_pwag033-B67","doi-asserted-by":"crossref","first-page":"eabi8683","DOI":"10.1126\/sciadv.abi8683","article-title":"Imaging and tracing the pattern of adult ovarian angiogenesis implies a strategy against female reproductive aging","volume":"8","author":"Xu","year":"2022","journal-title":"Sci Adv"},{"key":"2026093020541994900_pwag033-B68","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13059-015-0621-5","article-title":"The ensembl regulatory build","volume":"16","author":"Zerbino","year":"2015","journal-title":"Genome Biol"},{"key":"2026093020541994900_pwag033-B69","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.ajhg.2012.04.001","article-title":"A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia","volume":"90","author":"Zhao","year":"2012","journal-title":"Am J Hum Genet"},{"key":"2026093020541994900_pwag033-B70","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1007\/s00018-019-03101-9","article-title":"The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis","volume":"76","author":"Zhou","year":"2019","journal-title":"Cell Mol Life Sci"}],"container-title":["Protein &amp; Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/proteincell\/advance-article-pdf\/doi\/10.1093\/procel\/pwag033\/68370917\/pwag033.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/proteincell\/article-pdf\/17\/10\/934\/68370917\/pwag033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/proteincell\/article-pdf\/17\/10\/934\/68370917\/pwag033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:54:34Z","timestamp":1790816074000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/proteincell\/article\/17\/10\/934\/8690961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":71,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5,22]]},"published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/procel\/pwag033","relation":{},"ISSN":["1674-800X","1674-8018"],"issn-type":[{"value":"1674-800X","type":"print"},{"value":"1674-8018","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,5,22]]}}}