{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:21:38Z","timestamp":1790799698860,"version":"4.1.0"},"reference-count":199,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Starting Grant in Medicine and Health","award":["2022-01467"],"award-info":[{"award-number":["2022-01467"]}]},{"name":"Swedish Research Council and Birgitta and Carl-Axel Rydbeck Research","award":["2024-00208"],"award-info":[{"award-number":["2024-00208"]}]},{"name":"WORK4ALL","award":["2023-1-PT01-KA131-HED-000121324"],"award-info":[{"award-number":["2023-1-PT01-KA131-HED-000121324"]}]},{"name":"WORK4ALL","award":["2024-1-PT01-KA131-HED-000214636"],"award-info":[{"award-number":["2024-1-PT01-KA131-HED-000214636"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Human-induced pluripotent stem cells (hiPSCs) offer immense potential in reproductive medicine, particularly for males who lack germ cells and cannot achieve biological parenthood through conventional ARTs. Early efforts to derive human germ cells from stem cells were hindered by low efficiency, subpar characterization, and the lack of standardized differentiation approaches. However, recent advancements have led to the development of defined protocols that mimic early embryonic development and allow the specification of transcriptomically and epigenetically validated human primordial germ cell-like cells (hPGCLCs). Current research focuses on maturing hPGCLCs in vitro, particularly within 3D culture systems that resemble their physiological microenvironment, with the aim of producing transplantable hiPSC-derived spermatogonial stem cells (SSCs) or differentiating them to sperm. At the same time, researchers are also testing whether hiPSCs generated from infertile patients can resume germline differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE AND RATIONALE<\/jats:title>\n                    <jats:p>This narrative review aimed to summarize the key efforts and remaining challenges in differentiating male germ cells from human pluripotent stem cells (hPSCs), with a particular focus on defined and validated protocols for hPGCLC specification. In parallel, we addressed key safety and ethical considerations that must be accounted for the development of clinical applications. A deeper understanding of the approaching therapeutic use of hiPSCs in reproductive medicine is essential for developing novel regenerative fertility strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SEARCH METHODS<\/jats:title>\n                    <jats:p>PubMed, Scopus, and Web of Science were searched for studies attempting germ cell differentiation from hPSCs using relevant keywords (\u2018stem cells\u2019, \u2018human pluripotent stem cells\u2019, \u2018human embryonic stem cells\u2019, \u2018human induced pluripotent stem cells\u2019, \u2018somatic cell reprogramming\u2019, \u2018infertility\u2019, \u2018germline\u2019, \u2018spermatogenesis\u2019, \u2018germ cells\u2019, and \u2018primordial germ cells\u2019). No time period restriction was established. Studies with an exclusive focus on female germline differentiation were excluded. To maintain a human-focused perspective, only key animal studies are presented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OUTCOMES<\/jats:title>\n                    <jats:p>The literature reveals a clear segregation among protocols for deriving germ cells from hPSCs, particularly between earlier studies lacking standardized differentiation conditions and characterization, and the most recent, defined protocols having transcriptomic and epigenetic validation against in vivo hPGCs. Moreover, during the last decade, the field has seen remarkable progress, with multiple efforts aimed at maturing hPGCLCs, closely recapitulating late male embryonic germline development. Additionally, hiPSCs derived from male patients at risk of infertility, particularly those without underlying genetic syndromes, generally retain the capacity for early germline commitment. While attempts at maturating patient germ cells beyond the hPGCLC state remain limited, the rapid pace of discovery and refinement in recent years suggests that further breakthroughs, including clinically applicable fertility restoration strategies, are likely to be achieved in the near future.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS<\/jats:title>\n                    <jats:p>The ability to generate hiPSCs from infertile patients and to specify them into hPGCLCs supports the feasibility of obtaining hiPSC-derived SSCs for future therapeutic use. These advances raise important ethical, regulatory, and societal questions that must be actively discussed among researchers, clinicians, policymakers, and the general public to ensure responsible and equitable access to these technologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humupd\/dmaf029","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:05:50Z","timestamp":1763125550000},"page":"129-153","source":"Crossref","is-referenced-by-count":5,"title":["The road to restore male fertility using\n                    <i>in vitro<\/i>\n                    -derived germ cells"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-6053","authenticated-orcid":false,"given":"Tiago","family":"Macedo","sequence":"first","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet and Karolinska University Hospital , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-6988","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"Alves-Lopes","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet and Karolinska University Hospital , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"2026030500515393200_dmaf029-B1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s00418-021-02040-6","article-title":"NANOS3 downregulation in Down syndrome hiPSCs during primordial germ cell-like cell differentiation","volume":"157","author":"Abdyyev","year":"2022","journal-title":"Histochem Cell Biol"},{"key":"2026030500515393200_dmaf029-B2","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1089\/biores.2019.0046","article-title":"Induced pluripotent stem cells: reprogramming platforms and applications in cell replacement therapy","volume":"9","author":"Al Abbar","year":"2020","journal-title":"Biores Open Access"},{"key":"2026030500515393200_dmaf029-B3","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3390\/cells9041006","article-title":"The cellular impact of the ZIKA virus on male reproductive tract immunology and physiology","volume":"9","author":"Almeida","year":"2020","journal-title":"Cells"},{"key":"2026030500515393200_dmaf029-B4","doi-asserted-by":"publisher","first-page":"102008","DOI":"10.1016\/j.scr.2020.102008","article-title":"Establishment of iPSC lines from a high-grade Klinefelter Syndrome patient (49-XXXXY) and two genetically matched healthy relatives (KAUSTi003-A, KAUSTi004-A, KAUSTi004-B, KAUSTi005-A, KAUSTi005-B, KAUSTi005-C)","volume":"49","author":"Alowaysi","year":"2020","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B5","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1093\/humupd\/dmx036","article-title":"Testicular organoids: a new model to study the testicular microenvironment in vitro?","volume":"24","author":"Alves-Lopes","year":"2018","journal-title":"Hum Reprod Update"},{"key":"2026030500515393200_dmaf029-B6","doi-asserted-by":"publisher","first-page":"111907","DOI":"10.1016\/j.celrep.2022.111907","article-title":"Specification of human germ cell fate with enhanced progression capability supported by hindgut organoids","volume":"42","author":"Alves-Lopes","year":"2023","journal-title":"Cell Rep"},{"key":"2026030500515393200_dmaf029-B7","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1530\/jrf.0.1160379","article-title":"Expression of the homophilic adhesion molecule, Ep-CAM, in the mammalian germ line","volume":"116","author":"Anderson","year":"1999","journal-title":"J Reprod Fertil"},{"key":"2026030500515393200_dmaf029-B8","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.3390\/genes12081214","article-title":"DNA methylation dynamics in the female germline and maternal-effect mutations that disrupt genomic imprinting","volume":"12","author":"Anvar","year":"2021","journal-title":"Genes (Basel)"},{"key":"2026030500515393200_dmaf029-B9","doi-asserted-by":"publisher","first-page":"e9437","DOI":"10.15252\/emmm.201809437","article-title":"Should the 14-day rule for embryo research become the 28-day rule?","volume":"10","author":"Appleby","year":"2018","journal-title":"EMBO Mol Med"},{"key":"2026030500515393200_dmaf029-B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.stemcr.2019.12.004","article-title":"Recurrent genetic abnormalities in human pluripotent stem cells: definition and routine detection in culture supernatant by targeted droplet digital PCR","volume":"14","author":"Assou","year":"2020","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B11","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3390\/pharmaceutics14020317","article-title":"RNA-based strategies for cell reprogramming toward pluripotency","volume":"14","author":"Bailly","year":"2022","journal-title":"Pharmaceutics"},{"key":"2026030500515393200_dmaf029-B12","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1016\/j.stem.2021.04.001","article-title":"Principles of signaling pathway modulation for enhancing human naive pluripotency induction","volume":"28","author":"Bayerl","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B13","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/d41586-023-00755-1","article-title":"Eggs made from male mouse stem cells using error-prone culture","volume":"615","author":"Bayerl","year":"2023","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B14","author":"Bolton","year":"2023"},{"key":"2026030500515393200_dmaf029-B15","doi-asserted-by":"publisher","first-page":"567454","DOI":"10.3389\/fcell.2020.567454","article-title":"Modeling Klinefelter syndrome using induced pluripotent stem cells reveals impaired germ cell differentiation [brief research report]","volume":"8","author":"Botman","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2026030500515393200_dmaf029-B16","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/nature05950","article-title":"Derivation of pluripotent epiblast stem cells from mammalian embryos","volume":"448","author":"Brons","year":"2007","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1634\/stemcells.2007-1018","article-title":"A novel approach for the derivation of putative primordial germ cells and sertoli cells from human embryonic stem cells","volume":"27","author":"Bucay","year":"2009","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B18","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1038\/s41586-023-06424-7","article-title":"Transient naive reprogramming corrects hiPS cells functionally and epigenetically","volume":"620","author":"Buckberry","year":"2023","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B19","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1002\/stem.1392","article-title":"Essential role of Sox2 for the establishment and maintenance of the germ cell line","volume":"31","author":"Campolo","year":"2013","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B20","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1136\/medethics-2015-102964","article-title":"Good eggs? Evaluating consent forms for egg donation","volume":"42","author":"Cattapan","year":"2016","journal-title":"J Med Ethics"},{"key":"2026030500515393200_dmaf029-B21","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/s11019-017-9793-y","article-title":"Genome editing and assisted reproduction: curing embryos, society or prospective parents?","volume":"21","author":"Cavaliere","year":"2018","journal-title":"Med Health Care Philos"},{"key":"2026030500515393200_dmaf029-B22","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41392-024-01809-0","article-title":"Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications","volume":"9","author":"Cerneckis","year":"2024","journal-title":"Sig Transduct Target Ther"},{"key":"2026030500515393200_dmaf029-B23","doi-asserted-by":"publisher","first-page":"661","DOI":"10.3390\/ijms22020661","article-title":"Effects of survival motor neuron protein on germ cell development in mouse and human","volume":"22","author":"Chang","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026030500515393200_dmaf029-B24","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1093\/biolre\/iox138","article-title":"Germline competency of human embryonic stem cells depends on eomesodermin\u2020","volume":"97","author":"Chen","year":"2017","journal-title":"Biol Reprod"},{"key":"2026030500515393200_dmaf029-B25","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/s41392-022-01197-3","article-title":"Germline stem cells in human","volume":"7","author":"Cheng","year":"2022","journal-title":"Sig Transduct Target Ther"},{"key":"2026030500515393200_dmaf029-B26","doi-asserted-by":"publisher","first-page":"101596","DOI":"10.1016\/j.isci.2020.101596","article-title":"Unique epigenetic programming distinguishes regenerative spermatogonial stem cells in the developing mouse testis","volume":"23","author":"Cheng","year":"2020","journal-title":"iScience"},{"key":"2026030500515393200_dmaf029-B27","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/978-1-0716-3139-3_5","volume-title":"Spermatogonial Stem Cells: Methods and Protocols","author":"Cheng","year":"2023"},{"key":"2026030500515393200_dmaf029-B28","doi-asserted-by":"publisher","first-page":"114323","DOI":"10.1016\/j.celrep.2024.114323","article-title":"Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline","volume":"43","author":"Cheng","year":"2024","journal-title":"Cell Rep"},{"key":"2026030500515393200_dmaf029-B29","doi-asserted-by":"publisher","first-page":"14389","DOI":"10.1074\/jbc.M111.338434","article-title":"Meiotic competent human germ cell-like cells derived from human embryonic stem cells induced by BMP4\/WNT3A signaling and OCT4\/EpCAM (epithelial cell adhesion molecule) selection","volume":"287","author":"Chuang","year":"2012","journal-title":"J Biol Chem"},{"key":"2026030500515393200_dmaf029-B30","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1093\/hmg\/ddh088","article-title":"Spontaneous differentiation of germ cells from human embryonic stem cells in vitro","volume":"13","author":"Clark","year":"2004","journal-title":"Hum Mol Genet"},{"key":"2026030500515393200_dmaf029-B31","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.chom.2018.08.003","article-title":"Persistent marburg virus infection in the testes of nonhuman primate survivors","volume":"24","author":"Coffin","year":"2018","journal-title":"Cell Host Microbe"},{"key":"2026030500515393200_dmaf029-B32","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/s41556-024-01597-3","article-title":"Spatial transcriptomic characterization of a Carnegie stage 7 human embryo","volume":"27","author":"Cui","year":"2025","journal-title":"Nat Cell Biol"},{"key":"2026030500515393200_dmaf029-B33","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/s41587-022-01592-9","article-title":"Intellectual property and assisted reproductive technology","volume":"41","author":"Cyranoski","year":"2023","journal-title":"Nat Biotechnol"},{"key":"2026030500515393200_dmaf029-B34","doi-asserted-by":"publisher","first-page":"102475","DOI":"10.1016\/j.stemcr.2025.102475","article-title":"Safeguarding genomic imprints in naive human pluripotency","volume":"20","author":"De Los Angeles","year":"2025","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B35","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.3389\/fphys.2018.01413","article-title":"Haploid germ cells generated in organotypic culture of testicular tissue from prepubertal boys","volume":"9","author":"de Michele","year":"2018","journal-title":"Front Physiol"},{"key":"2026030500515393200_dmaf029-B36","doi-asserted-by":"publisher","first-page":"895528","DOI":"10.3389\/fendo.2022.895528","article-title":"Roles of spermatogonial stem cells in spermatogenesis and fertility restoration","volume":"13","author":"Diao","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026030500515393200_dmaf029-B37","doi-asserted-by":"publisher","first-page":"hoae010","DOI":"10.1093\/hropen\/hoae010","article-title":"A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey","volume":"2024","author":"Duffin","year":"2024","journal-title":"Hum Reprod Open"},{"key":"2026030500515393200_dmaf029-B38","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.celrep.2012.07.015","article-title":"Direct differentiation of human pluripotent stem cells into haploid spermatogenic cells","volume":"2","author":"Easley","year":"2012","journal-title":"Cell Rep"},{"key":"2026030500515393200_dmaf029-B39","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1002\/stem.672","article-title":"Complete meiosis from human induced pluripotent stem cells","volume":"29","author":"Eguizabal","year":"2011","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B40","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41572-023-00459-w","article-title":"Male infertility","volume":"9","author":"Eisenberg","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"2026030500515393200_dmaf029-B41","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/s41467-023-43871-2","article-title":"Derivation of human primordial germ cell-like cells in an embryonic-like culture","volume":"15","author":"Esfahani","year":"2024","journal-title":"Nat Commun"},{"key":"2026030500515393200_dmaf029-B42","doi-asserted-by":"publisher","first-page":"718","DOI":"10.3389\/fcell.2020.00432","article-title":"Induced pluripotent stem cells derived from two idiopathic azoospermia patients display compromised differentiation potential for primordial germ cell fate","volume":"8","author":"Fang","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2026030500515393200_dmaf029-B43","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.scr.2018.01.026","article-title":"Derivation of human induced pluripotent stem cell line (HUSTi001-A) from a 40-year-old patient with idiopathic infertility","volume":"27","author":"Fang","year":"2018","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B44","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1093\/humupd\/dmad028","article-title":"Declining global fertility rates and the implications for family planning and family building: an IFFS consensus document based on a narrative review of the literature","volume":"30","author":"Fauser","year":"2024","journal-title":"Hum Reprod Update"},{"key":"2026030500515393200_dmaf029-B45","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1111\/andr.13150","article-title":"An evaluation of changes over time in the semen parameters data used for the World Health Organization semen analysis reference ranges","volume":"10","author":"Feferkorn","year":"2022","journal-title":"Andrology"},{"key":"2026030500515393200_dmaf029-B46","author":"Fertility Europe","year":"2024"},{"key":"2026030500515393200_dmaf029-B47","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.fertnstert.2021.04.019","article-title":"Z-scores for comparative analyses of spermatogonial numbers throughout human development","volume":"116","author":"Funke","year":"2021","journal-title":"Fertil Steril"},{"key":"2026030500515393200_dmaf029-B48","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/nature12745","article-title":"Derivation of novel human ground state naive pluripotent stem cells","volume":"504","author":"Gafni","year":"2013","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B49","doi-asserted-by":"publisher","first-page":"677","DOI":"10.3390\/bioengineering11070677","article-title":"In vitro generation of haploid germ cells from human XY and XXY immature testes in a 3D organoid system","volume":"11","author":"Galdon","year":"2024","journal-title":"Bioengineering"},{"key":"2026030500515393200_dmaf029-B50","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1530\/RAF-21-0066","article-title":"Is there a valid ethical objection to the clinical use of in vitro-derived gametes?","volume":"2","author":"Galea","year":"2021","journal-title":"Reprod Fertil"},{"key":"2026030500515393200_dmaf029-B51","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41586-022-04918-4","article-title":"Single-cell roadmap of human gonadal development","volume":"607","author":"Garcia-Alonso","year":"2022","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B52","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3390\/biology12010070","article-title":"Decline of sperm quality over the last two decades in the South of Europe: a retrospective study in infertile patients","volume":"12","author":"Garcia-Grau","year":"2022","journal-title":"Biology (Basel)"},{"key":"2026030500515393200_dmaf029-B53","doi-asserted-by":"publisher","first-page":"3486","DOI":"10.1093\/humrep\/der351","article-title":"Hidden mosaicism in patients with Klinefelter\u2019s syndrome: implications for genetic reproductive counselling","volume":"26","author":"Garcia-Quevedo","year":"2011","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B54","doi-asserted-by":"publisher","first-page":"103681","DOI":"10.1016\/j.scr.2025.103681","article-title":"Generation of induced pluripotent stem cell line, NCHi028-A, from a male child with Prune Belly Syndrome","volume":"84","author":"Gomez Limia","year":"2025","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B55","doi-asserted-by":"publisher","first-page":"hoaa016","DOI":"10.1093\/hropen\/hoaa016","article-title":"Fertility preservation in boys: recent developments and new insights","volume":"2020","author":"Goossens","year":"2020","journal-title":"Hum Reprod Open"},{"key":"2026030500515393200_dmaf029-B56","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/pbc.24679","article-title":"The cyclophosphamide equivalent dose as an approach for quantifying alkylating agent exposure: a report from the Childhood Cancer Survivor Study","volume":"61","author":"Green","year":"2014","journal-title":"Pediatr Blood Cancer"},{"key":"2026030500515393200_dmaf029-B57","doi-asserted-by":"publisher","first-page":"102740","DOI":"10.1016\/j.scr.2022.102740","article-title":"Generation of iPS cell line (ICGi040-A) from skin fibroblasts of a patient with ring small supernumerary marker chromosome 4","volume":"61","author":"Gridina","year":"2022","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B58","doi-asserted-by":"publisher","first-page":"eade1257","DOI":"10.1126\/sciadv.ade1257","article-title":"Epigenetic resetting in the human germ line entails histone modification remodeling","volume":"9","author":"Gruhn","year":"2023","journal-title":"Sci Adv"},{"key":"2026030500515393200_dmaf029-B59","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12610-023-00193-z","article-title":"Viruses, bacteria and parasites: infection of the male genital tract and fertility","volume":"33","author":"Guiton","year":"2023","journal-title":"Basic Clin Androl"},{"key":"2026030500515393200_dmaf029-B60","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.stemcr.2016.02.005","article-title":"Naive pluripotent stem cells derived directly from isolated cells of the human inner cell mass","volume":"6","author":"Guo","year":"2016","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B61","doi-asserted-by":"publisher","first-page":"102453","DOI":"10.1016\/j.scr.2021.102453","article-title":"Generation of an iPSC line (HRMSDUi001-A) from an azoospermic patient with 45, XY, der(13;14)(q10;q10) karyotype","volume":"55","author":"Guo","year":"2021","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B62","doi-asserted-by":"publisher","first-page":"103257","DOI":"10.1016\/j.scr.2023.103257","article-title":"Generation of two isogenic sickle cell disease induced pluripotent stem cell lines from testicular fibroblasts","volume":"73","author":"Harancher","year":"2023","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B63","doi-asserted-by":"publisher","first-page":"dev202046","DOI":"10.1242\/dev.202046","article-title":"The developmental dynamics of the human male germline","volume":"150","author":"Hargy","year":"2023","journal-title":"Development"},{"key":"2026030500515393200_dmaf029-B64","doi-asserted-by":"publisher","first-page":"pgaf022","DOI":"10.1093\/pnasnexus\/pgaf022","article-title":"Trisomic rescue via allele-specific multiple chromosome cleavage using CRISPR-Cas9 in trisomy 21 cells","volume":"4","author":"Hashizume","year":"2025","journal-title":"PNAS Nexus"},{"key":"2026030500515393200_dmaf029-B65","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1126\/science.1226889","article-title":"Offspring from oocytes derived from in vitro primordial germ cell\u2013like cells in mice","volume":"338","author":"Hayashi","year":"2012","journal-title":"Science"},{"key":"2026030500515393200_dmaf029-B66","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.cell.2011.06.052","article-title":"Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells","volume":"146","author":"Hayashi","year":"2011","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B67","doi-asserted-by":"publisher","first-page":"e2410533","DOI":"10.1002\/advs.202410533","article-title":"X-linked gene dosage and SOX2 act as key roadblocks for human germ cell specification in Klinefelter Syndrome","volume":"12","author":"He","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"2026030500515393200_dmaf029-B68","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1093\/humrep\/dex256","article-title":"The importance of genetic parenthood for infertile men and women","volume":"32","author":"Hendriks","year":"2017","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B69","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.stem.2012.07.017","article-title":"Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm","volume":"11","author":"Hermann","year":"2012","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B70","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1093\/humrep\/deg348","article-title":"Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions","volume":"18","author":"Hopps","year":"2003","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B71","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/toxsci\/kfae060","article-title":"Microplastic presence in dog and human testis and its potential association with sperm count and weights of testis and epididymis","volume":"200","author":"Hu","year":"2024","journal-title":"Toxicol Sci"},{"key":"2026030500515393200_dmaf029-B72","doi-asserted-by":"publisher","first-page":"5656","DOI":"10.1038\/s41467-020-19350-3","article-title":"Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells","volume":"11","author":"Hwang","year":"2020","journal-title":"Nat Commun"},{"key":"2026030500515393200_dmaf029-B73","author":"International Society for Stem Cell Research","year":"2021"},{"key":"2026030500515393200_dmaf029-B74","author":"International Society for Stem Cell Research","year":"2025"},{"key":"2026030500515393200_dmaf029-B75","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1038\/s41556-023-01224-7","article-title":"DMRT1 regulates human germline commitment","volume":"25","author":"Irie","year":"2023","journal-title":"Nat Cell Biol"},{"key":"2026030500515393200_dmaf029-B76","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.cell.2014.12.013","article-title":"SOX17 is a critical specifier of human primordial germ cell fate","volume":"160","author":"Irie","year":"2015","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B77","doi-asserted-by":"publisher","first-page":"e31833","DOI":"10.1002\/pbc.31833","article-title":"Childhood cancer survivors in Latin America: insights into health outcomes and information needs","volume":"72","author":"Izurieta-Pacheco","year":"2025","journal-title":"Pediatr Blood Cancer"},{"key":"2026030500515393200_dmaf029-B78","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1093\/humrep\/dead243","article-title":"Results from the first autologous grafting of adult human testis tissue: a case report","volume":"39","author":"Jensen","year":"2024","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B79","doi-asserted-by":"publisher","first-page":"e72811","DOI":"10.7554\/eLife.72811","article-title":"Efficient differentiation of human primordial germ cells through geometric control reveals a key role for Nodal signaling","volume":"11","author":"Jo","year":"2022","journal-title":"Elife"},{"key":"2026030500515393200_dmaf029-B80","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1095\/biolreprod.103.017012","article-title":"Long-term proliferation in culture and germline transmission of mouse male germline stem cells","volume":"69","author":"Kanatsu-Shinohara","year":"2003","journal-title":"Biol Reprod"},{"key":"2026030500515393200_dmaf029-B81","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1089\/scd.2006.15.831","article-title":"Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells","volume":"15","author":"Kee","year":"2006","journal-title":"Stem Cells Dev"},{"key":"2026030500515393200_dmaf029-B82","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1038\/s41591-024-02990-z","article-title":"Two-year safety outcomes of iPS cell-derived mesenchymal stromal cells in acute steroid-resistant graft-versus-host disease","volume":"30","author":"Kelly","year":"2024","journal-title":"Nat Med"},{"key":"2026030500515393200_dmaf029-B83","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1016\/j.stemcr.2021.09.002","article-title":"Large-scale analysis of imprinting in naive human pluripotent stem cells reveals recurrent aberrations and a potential link to FGF signaling","volume":"16","author":"Keshet","year":"2021","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B84","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature09342","article-title":"Epigenetic memory in induced pluripotent stem cells","volume":"467","author":"Kim","year":"2010","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B85","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.stem.2024.12.005","article-title":"Pluripotent stem-cell-derived therapies in clinical trial: a 2025 update","volume":"32","author":"Kirkeby","year":"2025","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B86","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s12522-011-0077-6","article-title":"Reprogramming of adult human testicular cells by four transcription factors (OCT4, SOX2, KLF4, and C-MYC)","volume":"10","author":"Kobayashi","year":"2011","journal-title":"Reprod Med Biol"},{"key":"2026030500515393200_dmaf029-B87","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.stemcr.2022.01.012","article-title":"Expanding homogeneous culture of human primordial germ cell-like cells maintaining germline features without serum or feeder layers","volume":"17","author":"Kobayashi","year":"2022","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B88","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/nature22812","article-title":"Principles of early human development and germ cell program from conserved model systems","volume":"546","author":"Kobayashi","year":"2017","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B89","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1016\/j.stemcr.2023.03.005","article-title":"History and current status of clinical studies using human pluripotent stem cells","volume":"18","author":"Kobold","year":"2023","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B90","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41585-018-0003-3","article-title":"Genetics of male infertility","volume":"15","author":"Krausz","year":"2018","journal-title":"Nat Rev Urol"},{"key":"2026030500515393200_dmaf029-B91","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1038\/s41467-020-16323-4","article-title":"The mutational impact of culturing human pluripotent and adult stem cells","volume":"11","author":"Kuijk","year":"2020","journal-title":"Nat Commun"},{"key":"2026030500515393200_dmaf029-B92","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/bjh.19572","article-title":"Decreased spermatogonial numbers in boys with severe haematological diseases","volume":"205","author":"Lahtinen","year":"2024","journal-title":"Br J Haematol"},{"key":"2026030500515393200_dmaf029-B93","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1101\/gad.13.4.424","article-title":"Bmp4 is required for the generation of primordial germ cells in the mouse embryo","volume":"13","author":"Lawson","year":"1999","journal-title":"Genes Dev"},{"key":"2026030500515393200_dmaf029-B94","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/j.stemcr.2024.05.002","article-title":"Anticipating in vitro gametogenesis: hopes and concerns for IVG among diverse stakeholders","volume":"19","author":"Le Goff","year":"2024","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B95","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/d41586-023-00717-7","article-title":"The mice with two dads: scientists create eggs from male cells","volume":"615","author":"Ledford","year":"2023","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B96","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1038\/nm.3267","article-title":"Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies","volume":"19","author":"Lee","year":"2013","journal-title":"Nat Med"},{"key":"2026030500515393200_dmaf029-B97","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1038\/s12276-024-01359-z","article-title":"Epigenetic reprogramming in mouse and human primordial germ cells","volume":"56","author":"Lee","year":"2024","journal-title":"Exp Mol Med"},{"key":"2026030500515393200_dmaf029-B98","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1093\/humupd\/dmac035","article-title":"Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries","volume":"29","author":"Levine","year":"2023","journal-title":"Hum Reprod Update"},{"key":"2026030500515393200_dmaf029-B99","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.stem.2017.03.007","article-title":"Single-cell RNA-Seq analysis maps development of human germline cells and gonadal niche interactions","volume":"20","author":"Li","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B100","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41422-020-00401-9","article-title":"Dissecting the epigenomic dynamics of human fetal germ cell development at single-cell resolution","volume":"31","author":"Li","year":"2021","journal-title":"Cell Res"},{"key":"2026030500515393200_dmaf029-B101","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1038\/s41467-023-37820-2","article-title":"Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development","volume":"14","author":"Lismer","year":"2023","journal-title":"Nat Commun"},{"key":"2026030500515393200_dmaf029-B102","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12015-019-09935-x","article-title":"Advances in pluripotent stem cells: history, mechanisms, technologies, and applications","volume":"16","author":"Liu","year":"2020","journal-title":"Stem Cell Rev Rep"},{"key":"2026030500515393200_dmaf029-B103","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/s41586-025-08656-1","article-title":"Genome-coverage single-cell histone modifications for embryo lineage tracing","volume":"640","author":"Liu","year":"2025","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B104","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.stem.2023.02.008","article-title":"Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming","volume":"30","author":"Liuyang","year":"2023","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B105","doi-asserted-by":"publisher","first-page":"102583","DOI":"10.1016\/j.scr.2021.102583","article-title":"Generation of an induced pluripotent stem cell line GZHMCi008-A derived from a patient with SRY-positive 46, XX testicular disorder of sex development","volume":"57","author":"Luo","year":"2021","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B106","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.scr.2018.01.003","article-title":"Generation of an induced pluripotent stem cell line from an adult male with 45, X\/46, XY mosaicism","volume":"27","author":"Luo","year":"2018","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B107","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41587-024-02196-1","article-title":"Mapping the global landscape for induced pluripotent stem cells from patents and clinical trials","volume":"42","author":"Lyu","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2026030500515393200_dmaf029-B108","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/d41586-024-02915-3","article-title":"Human embryo models are getting more realistic\u2014raising ethical questions","volume":"633","author":"Mallapaty","year":"2024","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B109","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1056\/NEJMoa1608368","article-title":"Autologous induced stem-cell-derived retinal cells for macular degeneration","volume":"376","author":"Mandai","year":"2017","journal-title":"N Engl J Med"},{"key":"2026030500515393200_dmaf029-B110","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1080\/15592294.2019.1646572","article-title":"Epigenetic changes and assisted reproductive technologies","volume":"15","author":"Mani","year":"2020","journal-title":"Epigenetics"},{"key":"2026030500515393200_dmaf029-B111","doi-asserted-by":"publisher","first-page":"8340","DOI":"10.1038\/s41467-025-63454-7","article-title":"Induction of experimental cell division to generate cells with reduced chromosome ploidy","volume":"16","author":"Marti Gutierrez","year":"2025","journal-title":"Nat Commun"},{"key":"2026030500515393200_dmaf029-B112","doi-asserted-by":"publisher","first-page":"103657","DOI":"10.1016\/j.scr.2025.103657","article-title":"Generation, establishment and characterization of three pluripotent stem cell lines (CVTTHi002-A, CVTTHi003-A and CVTTHi004-A) from primary testicular somatic cells isolated from two prepuberal and one peripuberal Klinefelter Syndrome (47 XXY) patients","volume":"83","author":"Martin-Inaraja","year":"2025","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B113","doi-asserted-by":"publisher","first-page":"dev179564","DOI":"10.1242\/dev.179564","article-title":"Mapping cell migrations and fates in a gastruloid model to the human primitive streak","volume":"146","author":"Martyn","year":"2019","journal-title":"Development"},{"key":"2026030500515393200_dmaf029-B114","doi-asserted-by":"publisher","first-page":"7","DOI":"10.31083\/jomh.2021.016","article-title":"Chromosomal aneuploidies and associated rare genetic syndromes involved in male infertility","volume":"17","author":"Marzouni","year":"2021","journal-title":"J Mens Health"},{"key":"2026030500515393200_dmaf029-B115","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/stem.1012","article-title":"Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro","volume":"30","author":"Medrano","year":"2012","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B116","doi-asserted-by":"publisher","first-page":"950829","DOI":"10.3389\/fcvm.2022.950829","article-title":"Case report: transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy","volume":"9","author":"Miyagawa","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"2026030500515393200_dmaf029-B117","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13287-024-03690-8","article-title":"Pre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch","volume":"15","author":"Miyagawa","year":"2024","journal-title":"Stem Cell Res Ther"},{"key":"2026030500515393200_dmaf029-B118","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.1242\/dev.00640","article-title":"The chemokine SDF1\/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival","volume":"130","author":"Molyneaux","year":"2003","journal-title":"Development"},{"key":"2026030500515393200_dmaf029-B119","doi-asserted-by":"publisher","first-page":"14302","DOI":"10.1038\/s41598-022-17337-2","article-title":"iPSCs derived from infertile men carrying complex genetic abnormalities can generate primordial germ-like cells","volume":"12","author":"Mouka","year":"2022","journal-title":"Sci Rep"},{"key":"2026030500515393200_dmaf029-B120","doi-asserted-by":"publisher","first-page":"39760","DOI":"10.1038\/srep39760","article-title":"Induced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies","volume":"7","author":"Mouka","year":"2017","journal-title":"Sci Rep"},{"key":"2026030500515393200_dmaf029-B121","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/s41586-023-05834-x","article-title":"Generation of functional oocytes from male mice in vitro","volume":"615","author":"Murakami","year":"2023","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B122","doi-asserted-by":"publisher","first-page":"e104929","DOI":"10.15252\/embj.2020104929","article-title":"Long-term expansion with germline potential of human primordial germ cell-like cells in vitro","volume":"39","author":"Murase","year":"2020","journal-title":"EMBO J"},{"key":"2026030500515393200_dmaf029-B123","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s41586-024-07526-6","article-title":"In vitro reconstitution of epigenetic reprogramming in the human germ line","volume":"631","author":"Murase","year":"2024","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B124","author":"National Academies of Sciences, Engineering, and Medicine","year":"2023"},{"key":"2026030500515393200_dmaf029-B125","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1634\/stemcells.2007-0808","article-title":"CXCR4+\/FLK-1+ biomarkers select a cardiopoietic lineage from embryonic stem cells","volume":"26","author":"Nelson","year":"2008","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B126","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1111\/andr.12710","article-title":"Rebuilding the human testis in vitro","volume":"8","author":"Oliver","year":"2020","journal-title":"Andrology"},{"key":"2026030500515393200_dmaf029-B127","doi-asserted-by":"publisher","first-page":"100488","DOI":"10.1016\/j.crmeth.2023.100488","article-title":"Efficient and scalable generation of primordial germ cells in 2D culture using basement membrane extract overlay","volume":"3","author":"Overeem","year":"2023","journal-title":"Cell Rep Methods"},{"key":"2026030500515393200_dmaf029-B128","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1093\/humrep\/dez134","article-title":"Human induced pluripotent stem cells from two azoospermic patients with Klinefelter syndrome show similar X chromosome inactivation behavior to female pluripotent stem cells","volume":"34","author":"Panula","year":"2019","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B129","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1093\/hmg\/ddq520","article-title":"Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells","volume":"20","author":"Panula","year":"2011","journal-title":"Hum Mol Genet"},{"key":"2026030500515393200_dmaf029-B130","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1007\/s10815-019-01457-2","article-title":"Down syndrome and infertility: what support should we provide?","volume":"36","author":"Parizot","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"2026030500515393200_dmaf029-B131","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1002\/stem.13","article-title":"Derivation of primordial germ cells from human embryonic and induced pluripotent stem cells is significantly improved by coculture with human fetal gonadal cells","volume":"27","author":"Park","year":"2009","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B132","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1093\/humupd\/dmaa027","article-title":"Modelling human embryogenesis: embryo-like structures spark ethical and policy debate","volume":"26","author":"Pereira Daoud","year":"2020","journal-title":"Hum Reprod Update"},{"key":"2026030500515393200_dmaf029-B133","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1038\/s44319-025-00371-2","article-title":"Rapid human oogonia-like cell specification via transcription factor-directed differentiation","volume":"26","author":"Pierson Smela","year":"2025","journal-title":"EMBO Rep"},{"key":"2026030500515393200_dmaf029-B134","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41419-017-0234-x","article-title":"Genome-wide DNA methylation analysis reveals that mouse chemical iPSCs have closer epigenetic features to mESCs than OSKM-integrated iPSCs","volume":"9","author":"Ping","year":"2018","journal-title":"Cell Death Dis"},{"key":"2026030500515393200_dmaf029-B135","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1093\/stmcls\/sxac020","article-title":"Human induced pluripotent stem cells: from cell origin, genomic stability, and epigenetic memory to translational medicine","volume":"40","author":"Poetsch","year":"2022","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B136","doi-asserted-by":"publisher","first-page":"pkz008","DOI":"10.1093\/jncics\/pkz008","article-title":"Cancer treatment-related infertility: a critical review of the evidence","volume":"3","author":"Poorvu","year":"2019","journal-title":"JNCI Cancer Spectr"},{"key":"2026030500515393200_dmaf029-B137","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1093\/humrep\/dez180","article-title":"Assessment of fresh and cryopreserved testicular tissues from (pre)pubertal boys during organ culture as a strategy for in vitro spermatogenesis","volume":"34","author":"Portela","year":"2019","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B138","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1093\/humrep\/dew284","article-title":"Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts","volume":"32","author":"Punab","year":"2017","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B139","doi-asserted-by":"publisher","first-page":"382","DOI":"10.5534\/wjmh.210201","article-title":"Changes in semen analysis over time: a temporal trend analysis of 20 years of subfertile non-azoospermic men","volume":"41","author":"Punjani","year":"2023","journal-title":"World J Mens Health"},{"key":"2026030500515393200_dmaf029-B140","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2147\/tacg.S267421","article-title":"Y-chromosome microdeletions: a review of prevalence, screening, and clinical considerations","volume":"14","author":"Rabinowitz","year":"2021","journal-title":"Appl Clin Genet"},{"key":"2026030500515393200_dmaf029-B141","doi-asserted-by":"publisher","DOI":"10.1242\/dev.204968","article-title":"Emerging principles and models of human primordial germ cell development","volume":"152","author":"Ramakrishna","year":"2025","journal-title":"Development"},{"key":"2026030500515393200_dmaf029-B142","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1159\/000520412","article-title":"Epigenetic regulation during primordial germ cell development and differentiation","volume":"15","author":"Ramakrishna","year":"2021","journal-title":"Sex Dev"},{"key":"2026030500515393200_dmaf029-B143","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1016\/j.celrep.2014.03.067","article-title":"Fate of iPSCs derived from azoospermic and fertile men following xenotransplantation to murine seminiferous tubules","volume":"7","author":"Ramathal","year":"2014","journal-title":"Cell Rep"},{"key":"2026030500515393200_dmaf029-B144","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1111\/brv.12700","article-title":"Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis","volume":"96","author":"Ribas-Maynou","year":"2021","journal-title":"Biol Rev Camb Philos Soc"},{"key":"2026030500515393200_dmaf029-B145","doi-asserted-by":"publisher","first-page":"3548","DOI":"10.1016\/j.cell.2023.07.028","article-title":"An ethical framework for human embryology with embryo models","volume":"186","author":"Rivron","year":"2023","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B146","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/s41585-023-00723-4","article-title":"Human in vitro spermatogenesis as a regenerative therapy\u2014where do we stand?","volume":"20","author":"Robinson","year":"2023","journal-title":"Nat Rev Urol"},{"key":"2026030500515393200_dmaf029-B147","doi-asserted-by":"publisher","DOI":"10.1242\/dev.201797","article-title":"Technical challenges of studying early human development","volume":"150","author":"Rugg-Gunn","year":"2023","journal-title":"Development"},{"key":"2026030500515393200_dmaf029-B148","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1163\/17455243-4681062","article-title":"Preferring a genetically-related child","volume":"13","author":"Rulli","year":"2016","journal-title":"J Moral Philos"},{"key":"2026030500515393200_dmaf029-B149","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/s12967-022-03610-5","article-title":"Xeno-free induced pluripotent stem cell-derived neural progenitor cells for in vivo applications","volume":"20","author":"Rust","year":"2022","journal-title":"J Transl Med"},{"key":"2026030500515393200_dmaf029-B150","doi-asserted-by":"publisher","first-page":"eaaz6830","DOI":"10.1126\/science.aaz6830","article-title":"Mammalian in vitro gametogenesis","volume":"374","author":"Saitou","year":"2021","journal-title":"Science"},{"key":"2026030500515393200_dmaf029-B151","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.stem.2015.06.014","article-title":"Robust in vitro induction of human germ cell fate from pluripotent stem cells","volume":"17","author":"Sasaki","year":"2015","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B152","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1038\/s41586-025-08700-0","article-title":"Phase I\/II trial of iPS-cell-derived dopaminergic cells for Parkinson\u2019s disease","volume":"641","author":"Sawamoto","year":"2025","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B153","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1007\/s40121-022-00647-3","article-title":"Climate change and cascading risks from infectious disease","volume":"11","author":"Semenza","year":"2022","journal-title":"Infect Dis Ther"},{"key":"2026030500515393200_dmaf029-B154","doi-asserted-by":"publisher","first-page":"e531","DOI":"10.1002\/ctm2.531","article-title":"Impact of restoring male fertility with transplantation of in vitro propagated spermatogonial stem cells on the health of their offspring throughout life","volume":"11","author":"Serrano","year":"2021","journal-title":"Clin Transl Med"},{"key":"2026030500515393200_dmaf029-B155","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/nmat4829","article-title":"Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche","volume":"16","author":"Shao","year":"2017","journal-title":"Nat Mater"},{"key":"2026030500515393200_dmaf029-B156","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1111\/andr.13033","article-title":"Postpubertal spermatogonial stem cell transplantation restores functional sperm production in rhesus monkeys irradiated before and after puberty","volume":"9","author":"Shetty","year":"2021","journal-title":"Andrology"},{"key":"2026030500515393200_dmaf029-B157","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s12522-015-0213-9","article-title":"Derivation of integration-free iPSCs from a Klinefelter syndrome patient","volume":"15","author":"Shimizu","year":"2016","journal-title":"Reprod Med Biol"},{"key":"2026030500515393200_dmaf029-B158","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1242\/dev.142679","article-title":"Formative pluripotency: the executive phase in a developmental continuum","volume":"144","author":"Smith","year":"2017","journal-title":"Development"},{"key":"2026030500515393200_dmaf029-B159","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1093\/humrep\/dey240","article-title":"Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy","volume":"33","author":"Stukenborg","year":"2018","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B160","doi-asserted-by":"publisher","first-page":"e07686","DOI":"10.1016\/j.heliyon.2021.e07686","article-title":"Alternative to FBS in animal cell culture\u2014an overview and future perspective","volume":"7","author":"Subbiahanadar Chelladurai","year":"2021","journal-title":"Heliyon"},{"key":"2026030500515393200_dmaf029-B161","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B162","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B163","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1016\/j.cell.2014.08.029","article-title":"Resetting transcription factor control circuitry toward ground-state pluripotency in human","volume":"158","author":"Takashima","year":"2014","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B164","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/j.cell.2015.04.053","article-title":"A unique gene regulatory network resets the human germline epigenome for development","volume":"161","author":"Tang","year":"2015","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B165","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/nrg.2016.88","article-title":"Specification and epigenetic programming of the human germ line","volume":"17","author":"Tang","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2026030500515393200_dmaf029-B166","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1093\/humrep\/dead197","article-title":"ART in Europe, 2019: results generated from European registries by ESHRE","volume":"38","author":"The European IVF Monitoring Consortium for the European Society of Human Reproduction and Embryology","year":"2023","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B167","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.stem.2014.07.002","article-title":"Systematic identification of culture conditions for induction and maintenance of naive human pluripotency","volume":"15","author":"Theunissen","year":"2014","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B168","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic stem cell lines derived from human blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"2026030500515393200_dmaf029-B169","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/s41586-021-04158-y","article-title":"Single-cell transcriptomic characterization of a gastrulating human embryo","volume":"600","author":"Tyser","year":"2021","journal-title":"Nature"},{"key":"2026030500515393200_dmaf029-B170","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1093\/humrep\/dez043","article-title":"Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers","volume":"34","author":"Valli-Pulaski","year":"2019","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B171","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1093\/stmcls\/sxad065","article-title":"Automated generation of hiPSC-derived hepatic progeny by cost-efficient compounds","volume":"41","author":"Vanmarcke","year":"2023","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B172","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.radonc.2015.10.001","article-title":"Fertility in childhood cancer survivors following cranial irradiation for primary central nervous system and skull base tumors","volume":"117","author":"Vern-Gross","year":"2015","journal-title":"Radiother Oncol"},{"key":"2026030500515393200_dmaf029-B173","doi-asserted-by":"publisher","first-page":"5690","DOI":"10.1038\/s41467-023-41302-w","article-title":"Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification","volume":"14","author":"Vijayakumar","year":"2023","journal-title":"Nat Commun"},{"key":"2026030500515393200_dmaf029-B174","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.devcel.2016.09.015","article-title":"Comparative principles of DNA methylation reprogramming during human and mouse in vitro primordial germ cell specification","volume":"39","author":"von Meyenn","year":"2016","journal-title":"Dev Cell"},{"key":"2026030500515393200_dmaf029-B175","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.cell.2015.05.039","article-title":"Forget the parents: epigenetic reprogramming in human germ cells","volume":"161","author":"von Meyenn","year":"2015","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B176","doi-asserted-by":"publisher","first-page":"e6143","DOI":"10.7717\/peerj.6143","article-title":"Efficient generation of human primordial germ cell-like cells from pluripotent stem cells in a methylcellulose-based 3D system at large scale","volume":"6","author":"Wang","year":"2019","journal-title":"PeerJ"},{"key":"2026030500515393200_dmaf029-B177","doi-asserted-by":"publisher","first-page":"101703","DOI":"10.1016\/j.scr.2020.101703","article-title":"Generation of an iPSC line (HUSTi002-A) from fibroblasts of a patient with Sertoli cell-only syndrome carrying c.731_732delAT in PIWIL2 gene","volume":"42","author":"Wang","year":"2020","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B178","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/nmeth.3016","article-title":"A method to recapitulate early embryonic spatial patterning in human embryonic stem cells","volume":"11","author":"Warmflash","year":"2014","journal-title":"Nat Methods"},{"key":"2026030500515393200_dmaf029-B179","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s41589-025-01874-8","article-title":"Chemical-based epigenetic reprogramming to advance pluripotency and totipotency","volume":"21","author":"Wen","year":"2025","journal-title":"Nat Chem Biol"},{"key":"2026030500515393200_dmaf029-B180","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1093\/humrep\/deg143","article-title":"Human embryonic stem cells: research, ethics and policy","volume":"18","author":"Wert","year":"2003","journal-title":"Human Reproduction"},{"key":"2026030500515393200_dmaf029-B181","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1634\/stemcells.2008-0124","article-title":"Enrichment and differentiation of human germ-like cells mediated by feeder cells and basic fibroblast growth factor signaling","volume":"26","author":"West","year":"2008","journal-title":"Stem Cells"},{"key":"2026030500515393200_dmaf029-B182","author":"World Health Organization","year":"2021"},{"key":"2026030500515393200_dmaf029-B183","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1093\/humrep\/den272","article-title":"Long-term spermatogonial survival in cryopreserved and xenografted immature human testicular tissue","volume":"23","author":"Wyns","year":"2008","journal-title":"Hum Reprod"},{"key":"2026030500515393200_dmaf029-B184","doi-asserted-by":"publisher","first-page":"2855","DOI":"10.1016\/j.cell.2024.03.041","article-title":"3D reconstruction of a gastrulating human embryo","volume":"187","author":"Xiao","year":"2024","journal-title":"Cell"},{"key":"2026030500515393200_dmaf029-B185","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.stemcr.2017.01.022","article-title":"Reversal of phenotypic abnormalities by CRISPR\/Cas9-mediated gene correction in huntington disease patient-derived induced pluripotent stem cells","volume":"8","author":"Xu","year":"2017","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B186","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.stemcr.2017.01.022","article-title":"Reversal of phenotypic abnormalities by CRISPR\/Cas9-mediated gene correction in Huntington disease patient-derived induced pluripotent stem cells","volume":"8","author":"Xu","year":"2017","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B187","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1126\/science.aat1674","article-title":"Generation of human oogonia from induced pluripotent stem cells in vitro","volume":"362","author":"Yamashiro","year":"2018","journal-title":"Science"},{"key":"2026030500515393200_dmaf029-B188","doi-asserted-by":"publisher","first-page":"102397","DOI":"10.1016\/j.scr.2021.102397","article-title":"Generation of a human induced pluripotent stem cell line (SMUSHi001-A) from a patient with 46, XX male sex reversal syndrome carrying the SRY gene","volume":"54","author":"Yan","year":"2021","journal-title":"Stem Cell Res"},{"key":"2026030500515393200_dmaf029-B189","doi-asserted-by":"publisher","first-page":"7858","DOI":"10.1073\/pnas.151242798","article-title":"Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways","volume":"98","author":"Ying","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026030500515393200_dmaf029-B190","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1093\/biolre\/iox038","article-title":"Clonal variation of human induced pluripotent stem cells for induction into the germ cell fate","volume":"96","author":"Yokobayashi","year":"2017","journal-title":"Biol Reprod"},{"key":"2026030500515393200_dmaf029-B191","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.stem.2020.11.003","article-title":"Derivation of intermediate pluripotent stem cells amenable to primordial germ cell specification","volume":"28","author":"Yu","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2026030500515393200_dmaf029-B192","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13287-019-1165-5","article-title":"Stem cells: past, present, and future","volume":"10","author":"Zakrzewski","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"2026030500515393200_dmaf029-B193","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.neuroscience.2016.09.001","article-title":"CXCR4 activation promotes differentiation of human embryonic stem cells to neural stem cells","volume":"337","author":"Zhang","year":"2016","journal-title":"Neuroscience"},{"key":"2026030500515393200_dmaf029-B194","doi-asserted-by":"publisher","first-page":"162713","DOI":"10.1016\/j.scitotenv.2023.162713","article-title":"Detection and characterization of microplastics in the human testis and semen","volume":"877","author":"Zhao","year":"2023","journal-title":"Sci Total Environ"},{"key":"2026030500515393200_dmaf029-B195","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.stemcr.2018.01.001","article-title":"In vitro modeling of human germ cell development using pluripotent stem cells","volume":"10","author":"Zhao","year":"2018","journal-title":"Stem Cell Reports"},{"key":"2026030500515393200_dmaf029-B196","doi-asserted-by":"publisher","first-page":"112379","DOI":"10.1016\/j.celrep.2023.112379","article-title":"Induction and application of human naive pluripotency","volume":"42","author":"Zhou","year":"2023","journal-title":"Cell Rep"},{"key":"2026030500515393200_dmaf029-B197","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1089\/scd.2012.0260","article-title":"Generation and characterization of human cryptorchid-specific induced pluripotent stem cells from urine","volume":"22","author":"Zhou","year":"2013","journal-title":"Stem Cells Dev"},{"key":"2026030500515393200_dmaf029-B198","doi-asserted-by":"publisher","first-page":"104728","DOI":"10.1016\/j.isci.2022.104728","article-title":"Patent bibliometric analysis for global trend of organoid technologies in the past decade","volume":"25","author":"Zhu","year":"2022","journal-title":"iScience"},{"key":"2026030500515393200_dmaf029-B199","doi-asserted-by":"publisher","author":"Zielen","year":"2025","DOI":"10.1101\/2025.03.25.25324518"}],"container-title":["Human Reproduction Update"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humupd\/article-pdf\/32\/2\/129\/66032630\/dmaf029.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humupd\/article-pdf\/32\/2\/129\/66032630\/dmaf029.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:52:05Z","timestamp":1772689925000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humupd\/article\/32\/2\/129\/8384139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":199,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,12,19]]},"published-print":{"date-parts":[[2026,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humupd\/dmaf029","relation":{},"ISSN":["1355-4786","1460-2369"],"issn-type":[{"value":"1355-4786","type":"print"},{"value":"1460-2369","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2025,12,19]]}}}