{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:51:47Z","timestamp":1785408707292,"version":"3.56.0"},"reference-count":103,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705803"],"award-info":[{"award-number":["2023YFC2705803"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471767"],"award-info":[{"award-number":["82471767"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82471767"],"award-info":[{"award-number":["82471767"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Biallelic mutations of NLRP7, a maternal-effect gene encoding a key component of the subcortical maternal complex, are the major monogenic cause of recurrent hydatidiform mole (RHM) and confer a substantial lifetime risk of gestational trophoblastic neoplasia (GTN), including choriocarcinoma. Although oocyte donation is currently the standard reproductive option, anecdotal live births from autologous oocytes in carriers of specific missense variants raise mechanistic and clinical questions that have not been integrated. We aimed to synthesize the current understanding of NLRP7 biology, oncogenic mechanisms in GTN, and genotype-stratified reproductive outcomes, and to propose a genetic permissiveness framework that links cancer surveillance with reproductive decision-making. We also place this monogenic disease in an epidemiological context, given the marked geographical variation in molar pregnancy incidence. Methods: PubMed, Embase and Web of Science were searched from January 2006 to December 2025 using terms related to NLRP7, hydatidiform mole, GTN, choriocarcinoma, maternal-effect genes, genomic imprinting, and assisted reproduction. Original studies, case series, expert consensus statements, and reviews were included. Results: NLRP7 loss disrupts subcortical maternal complex assembly, maternal-DMR methylation, trophoblast differentiation, and HLA-C-dependent immune privilege; in choriocarcinoma, NLRP7 is conversely reported to be up-regulated, where it has been implicated in tumor proliferation and immune evasion through inflammasome-independent pathways. Genetic permissiveness for autologous-oocyte pregnancy is mutation-type dependent: complete loss-of-function variants confer near-zero permissiveness, whereas missense variants with retained partial function may permit rare normal pregnancies. Conclusions: A genetic-permissiveness framework integrating variant-level functional data, GTN risk, and reproductive priorities can support shared decision-making in this rare but high-stakes clinical scenario, and it identifies clear directions for future translational research. We emphasize, however, that this framework has not been prospectively validated and should be regarded as hypothesis-generating rather than as a clinically established decision-making model. Recognizing the biallelic NLRP7 mutation as a heritable cancer-predisposition state further supports genotype-informed, risk-stratified oncological surveillance.<\/jats:p>","DOI":"10.3390\/cancers18152386","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"2386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NLRP7 in Hydatidiform Mole and Gestational Trophoblastic Neoplasia: From Maternal-Effect Biology to a Genetic Permissiveness Framework for Integrated Cancer Surveillance and Reproductive Decision-Making"],"prefix":"10.3390","volume":"18","author":[{"given":"Wei","family":"Xue","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Women\u2019s Health and Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Chen","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Women\u2019s Health and Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9112-1021","authenticated-orcid":false,"given":"Yang","family":"Xiang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Women\u2019s Health and Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-0119","authenticated-orcid":false,"given":"Junjun","family":"Yang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Women\u2019s Health and Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhu, T., Zhu, G., Ma, J., Yu, X., Chen, T., Tao, X., Sun, L., Lu, X., and Du, Y. (2025). Demographics, risk factors associated with malignant progression, and pregnancy outcomes of hydatidiform mole: A retrospective cohort study in Shanghai, China. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1643590"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0140-6736(10)60280-2","article-title":"Gestational trophoblastic disease","volume":"376","author":"Seckl","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.ajog.2010.06.073","article-title":"Gestational trophoblastic disease I: Epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole","volume":"203","author":"Lurain","year":"2010","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/S1470-2045(03)01245-2","article-title":"Epidemiology and aetiology of gestational trophoblastic diseases","volume":"4","author":"Altieri","year":"2003","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/oxfordjournals.epirev.a036275","article-title":"Epidemiology of hydatidiform mole and choriocarcinoma","volume":"6","author":"Bracken","year":"1984","journal-title":"Epidemiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/AOG.0b013e3181802186","article-title":"Maternal age-related rates of gestational trophoblastic disease","volume":"112","author":"Altman","year":"2008","journal-title":"Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.hoc.2024.07.003","article-title":"Epidemiology of gestational trophoblastic disease","volume":"38","author":"Joneborg","year":"2024","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e000321","DOI":"10.1136\/bmjmed-2022-000321","article-title":"Advances in the diagnosis and early management of gestational trophoblastic disease","volume":"1","author":"Joyce","year":"2022","journal-title":"BMJ Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"424","DOI":"10.31083\/j.ceog.2020.03.5215","article-title":"Recurrent hydatidiform mole: When to stop?","volume":"47","author":"Ozbasli","year":"2020","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1080\/01443615.2021.1997958","article-title":"A case report on recurrent partial moles in three consecutive pregnancies","volume":"42","author":"Dalmia","year":"2022","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1093\/humrep\/dev169","article-title":"Risk of recurrent molar pregnancies following complete and partial hydatidiform moles","volume":"30","author":"Eagles","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1002\/humu.24439","article-title":"Biallelic NLRP7 variants in patients with recurrent hydatidiform mole: A review and expert consensus","volume":"43","author":"Slim","year":"2022","journal-title":"Hum. Mutat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/ng1740","article-title":"Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans","volume":"38","author":"Murdoch","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_14","first-page":"1103","article-title":"Chinese expert consensus on the diagnosis and treatment of hydatidiform mole (2024 edition)","volume":"40","author":"Lu","year":"2024","journal-title":"Chin. J. Pract. Gynecol. Obstet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Slim, R., and Wallace, E.P. (2013). NLRP7 and the genetics of hydatidiform moles: Recent advances and new challenges. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00242"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s13669-013-0076-1","article-title":"Genetics and epigenetics of recurrent hydatidiform moles: Basic science and genetic counselling","volume":"3","author":"Nguyen","year":"2014","journal-title":"Curr. Obstet. Gynecol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R161","DOI":"10.1530\/REP-17-0465","article-title":"NLRPs, the subcortical maternal complex and genomic imprinting","volume":"154","author":"Monk","year":"2017","journal-title":"Reproduction"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bpobgyn.2021.01.004","article-title":"Genetics of gestational trophoblastic disease","volume":"74","author":"Fisher","year":"2021","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/imm.13372","article-title":"NLRP7: From inflammasome regulation to human disease","volume":"163","author":"Carriere","year":"2021","journal-title":"Immunology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s00428-020-02802-y","article-title":"Germline NLRP7 mutations: Genomic imprinting and hydatidiform mole","volume":"477","author":"Hui","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.rbmo.2015.03.011","article-title":"Live births in women with recurrent hydatidiform mole and two NLRP7 mutations","volume":"31","author":"Akoury","year":"2015","journal-title":"Reprod. Biomed. Online"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sanchez-Delgado, M., Martin-Trujillo, A., Tayama, C., Vidal, E., Esteller, M., Iglesias-Platas, I., Deo, N., Barney, O., Maclean, K., and Hata, K. (2015). Absence of maternal methylation in biparental hydatidiform moles from women with NLRP7 maternal-effect mutations reveals widespread placenta-specific imprinting. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005644"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"114022","DOI":"10.1016\/j.ejogrb.2025.114022","article-title":"Is gestational trophoblastic neoplasia more common among women with recurrent hydatidiform moles and biallelic NLRP7 mutations? A 17-year prospective study from India","volume":"311","author":"Bagga","year":"2025","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100803","DOI":"10.1016\/j.gore.2021.100803","article-title":"High-risk gestational trophoblastic neoplasia from a homozygous NLRP7 mutation","volume":"37","author":"Kopelman","year":"2021","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/15513815.2020.1852463","article-title":"Detection of parental contribution to molar genome leads to diagnosis of recurrent hydatidiform mole in a family with NLRP7 variants","volume":"41","author":"Wang","year":"2022","journal-title":"Fetal Pediatr. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Reynaud, D., Abi Nahed, R., Lemaitre, N., Bolze, P.A., Traboulsi, W., Sergent, F., Battail, C., Filhol, O., Sapin, V., and Boufettal, H. (2021). NLRP7 promotes choriocarcinoma growth and progression through the establishment of an immunosuppressive microenvironment. Cancers, 13.","DOI":"10.3390\/cancers13122999"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Reynaud, D., Alfaidy, N., Collet, C., Lemaitre, N., Sergent, F., Miege, C., Soleilhac, E., Al Assi, A., Murthi, P., and Courtois, G. (2023). NLRP7 enhances choriocarcinoma cell survival and camouflage in an inflammasome-independent pathway. Cells, 12.","DOI":"10.3390\/cells12060857"},{"key":"ref_28","first-page":"77","article-title":"Research progress on familial recurrent hydatidiform mole","volume":"30","author":"Lei","year":"2021","journal-title":"Chin. J. Hum. Sex."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1007\/s10815-021-02132-1","article-title":"The genetics of recurrent hydatidiform moles in Mexico: Further evidence of a strong founder effect for one mutation in NLRP7","volume":"38","author":"Aguinaga","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102361","DOI":"10.1016\/j.scr.2021.102361","article-title":"Reprogramming of human peripheral blood mononuclear cells from a patient suffering from recurrent hydatidiform mole to an iPSC line","volume":"53","author":"Gong","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1530\/REP-19-0081","article-title":"NLRP7 is expressed in the ovine ovary and associated with in vitro pre-implantation embryo development","volume":"158","author":"Li","year":"2019","journal-title":"Reproduction"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/cei.13472","article-title":"Abnormal processing of IL-1\u03b2 in NLRP7-mutated monocytes in hydatidiform mole patients","volume":"202","author":"Zhang","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tian, X., Pascal, G., and Monget, P. (2009). Evolution and functional divergence of NLRP genes in mammalian reproductive systems. BMC Evol. Biol., 9.","DOI":"10.1186\/1471-2148-9-202"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.devcel.2008.07.010","article-title":"A subcortical maternal complex essential for preimplantation mouse embryogenesis","volume":"15","author":"Li","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ajhg.2011.08.002","article-title":"Mutations causing familial biparental hydatidiform mole implicate C6orf221 as a possible regulator of genomic imprinting in the human oocyte","volume":"89","author":"Parry","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Meyer, E., Lim, D., Pasha, S., Tee, L.J., Rahman, F., Yates, J.R.W., Woods, C.G., Reik, W., and Maher, E.R. (2009). Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith-Wiedemann syndrome). PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000423"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.ajhg.2016.06.024","article-title":"Mutations in PADI6 cause female infertility characterized by early embryonic arrest","volume":"99","author":"Xu","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s13059-015-0792-0","article-title":"TLE6 mutation causes the earliest known human embryonic lethality","volume":"16","author":"Alazami","year":"2015","journal-title":"Genome Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1136\/jmedgenet-2018-105936","article-title":"Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest","volume":"56","author":"Mu","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"gaab043","DOI":"10.1093\/molehr\/gaab043","article-title":"The subcortical maternal complex: Emerging roles and novel perspectives","volume":"27","author":"Bebbere","year":"2021","journal-title":"Mol. Hum. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1242\/dev.016329","article-title":"Role for PADI6 and the cytoplasmic lattices in ribosomal storage in oocytes and translational control in the early mouse embryo","volume":"135","author":"Yurttas","year":"2008","journal-title":"Development"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/ejhg.2012.274","article-title":"Report of four new patients with protein-truncating mutations in C6orf221\/KHDC3L and colocalization with NLRP7","volume":"21","author":"Reddy","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s00109-023-02322-7","article-title":"NLRP7 participates in the human subcortical maternal complex and its variants cause female infertility characterized by early embryo arrest","volume":"101","author":"Han","year":"2023","journal-title":"J. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41594-023-01153-x","article-title":"Structural basis of the subcortical maternal complex and its implications in reproductive disorders","volume":"31","author":"Chi","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1038\/s41594-024-01396-2","article-title":"Cryo-EM structure of the human subcortical maternal complex and the associated discovery of infertility-associated variants","volume":"31","author":"Chi","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s42003-025-07571-5","article-title":"NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing","volume":"8","author":"Chen","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/35047554","article-title":"Genomic imprinting: Parental influence on the genome","volume":"2","author":"Reik","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"a002592","DOI":"10.1101\/cshperspect.a002592","article-title":"Mammalian genomic imprinting","volume":"3","author":"Bartolomei","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1007\/s10815-021-02312-z","article-title":"NLRP7 variants in spontaneous abortions with multilocus imprinting disturbances from women with recurrent pregnancy loss","volume":"38","author":"Sazhenova","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Anvar, Z., Chakchouk, I., Demond, H., Sharif, M., Kelsey, G., and Van den Veyver, I.B. (2021). DNA methylation dynamics in the female germline and maternal-effect mutations that disrupt genomic imprinting. Genes, 12.","DOI":"10.3390\/genes12081214"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/humrep\/deu291","article-title":"NLRP7 and KHDC3L, the two maternal-effect proteins responsible for recurrent hydatidiform moles, co-localize to the oocyte cytoskeleton","volume":"30","author":"Akoury","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"44667","DOI":"10.1038\/srep44667","article-title":"Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming","volume":"7","author":"Mahadevan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/hmg\/ddt457","article-title":"NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation","volume":"23","author":"Mahadevan","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nature02633","article-title":"Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting","volume":"429","author":"Kaneda","year":"2004","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1126\/science.1065848","article-title":"Dnmt3L and the establishment of maternal genomic imprints","volume":"294","author":"Xu","year":"2001","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1101\/gad.1667008","article-title":"Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development","volume":"22","author":"Hirasawa","year":"2008","journal-title":"Genes Dev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0092-8674(01)00280-X","article-title":"Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene","volume":"104","author":"Howell","year":"2001","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/ncb1519","article-title":"PGC7\/Stella protects against DNA demethylation in early embryogenesis","volume":"9","author":"Nakamura","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.devcel.2008.08.014","article-title":"A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints","volume":"15","author":"Li","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1101\/gad.320069.118","article-title":"ZNF445 is a primary regulator of genomic imprinting","volume":"33","author":"Takahashi","year":"2019","journal-title":"Genes Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.molcel.2011.08.032","article-title":"In embryonic stem cells, ZFP57\/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions","volume":"44","author":"Quenneville","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1038\/s41467-026-69744-y","article-title":"TCL1A mediates DNA methylation defects in recurrent hydatidiform mole with NLRP7 pathogenic variants","volume":"17","author":"Gao","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"dev163428","DOI":"10.1242\/dev.163428","article-title":"Development of the human placenta","volume":"146","author":"Turco","year":"2019","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1007\/s11427-025-3191-5","article-title":"Single-nucleus multi-omics dissection of dysregulated trophoblast development and disrupted immune microenvironment in complete hydatidiform moles","volume":"69","author":"Chen","year":"2026","journal-title":"Sci. China Life Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Abi Nahed, R., Elkhoury Mikhael, M., Reynaud, D., Collet, C., Lemaitre, N., Michy, T., Hoffmann, P., Sergent, F., Marquette, C., and Murthi, P. (2022). Role of NLRP7 in normal and malignant trophoblast cells. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020252"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"E1212","DOI":"10.1073\/pnas.1303094110","article-title":"Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4","volume":"110","author":"Amita","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.stem.2017.11.004","article-title":"Derivation of human trophoblast stem cells","volume":"22","author":"Okae","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e2404229121","DOI":"10.1073\/pnas.2404229121","article-title":"HLA-C expression in extravillous trophoblasts is determined by an ELF3-NLRP2\/NLRP7 regulatory axis","volume":"121","author":"Gu","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nri1897","article-title":"Immunology of placentation in eutherian mammals","volume":"6","author":"Moffett","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1053\/plac.1999.0496","article-title":"Surface expression of HLA-C antigen by human extravillous trophoblast","volume":"21","author":"King","year":"2000","journal-title":"Placenta"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e2509798122","DOI":"10.1073\/pnas.2509798122","article-title":"Modulation of the PGRMC1\/NLRP7\/HLA-C axis by autophagy is linked to both spontaneous preterm birth and gestational choriocarcinoma","volume":"122","author":"Li","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.it.2008.02.012","article-title":"A critical look at HLA-G","volume":"29","author":"Apps","year":"2008","journal-title":"Trends Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1126\/science.2326636","article-title":"A class I antigen, HLA-G, expressed in human trophoblasts","volume":"248","author":"Kovats","year":"1990","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1093\/hmg\/ddn418","article-title":"NLRP7 mutations in women with diploid androgenetic and triploid moles: A proposed mechanism for mole formation","volume":"18","author":"Deveault","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00428-020-02769-w","article-title":"A novel NLRP7 protein-truncating mutation associated with discordant and divergent p57 immunostaining in diploid biparental and triploid digynic moles","volume":"477","author":"Allias","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/jjco\/hyz036","article-title":"NLRP7 and KHDC3L variants in Chinese patients with recurrent hydatidiform moles","volume":"49","author":"Ji","year":"2019","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1097\/00000478-200110000-00001","article-title":"Discrimination of complete hydatidiform mole from its mimics by immunohistochemistry of the paternally imprinted gene product p57KIP2","volume":"25","author":"Castrillon","year":"2001","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/modpathol.2013.143","article-title":"Characteristics of hydatidiform moles: Analysis of a prospective series with p57 immunohistochemistry and molecular genotyping","volume":"27","author":"Banet","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/cge.14288","article-title":"De novo pathogenic variations of NLRP7 increasing the risk of gestational trophoblastic neoplasia","volume":"103","author":"Tao","year":"2023","journal-title":"Clin. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/ejhg.2017.94","article-title":"Maternal heterozygous NLRP7 variant results in recurrent reproductive failure and imprinting disturbances in the offspring","volume":"25","author":"Soellner","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/humu.9498","article-title":"Women heterozygous for NALP7\/NLRP7 mutations are at risk for reproductive wastage: Report of two novel mutations","volume":"28","author":"Qian","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1136\/jmg.2011.089144","article-title":"NLRP7 in the spectrum of reproductive wastage: Rare non-synonymous variants confer genetic susceptibility to recurrent reproductive wastage","volume":"48","author":"Messaed","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8086","DOI":"10.1038\/ncomms9086","article-title":"Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans","volume":"6","author":"Docherty","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejogrb.2013.06.028","article-title":"Novel NLRP7 mutations in familial recurrent hydatidiform mole: Are NLRP7 mutations a risk for recurrent reproductive wastage?","volume":"170","author":"Ulker","year":"2013","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/cge.13941","article-title":"Novel pathogenic variants in NLRP7, NLRP5 and PADI6 in patients with recurrent hydatidiform moles and reproductive failure","volume":"99","author":"Rezaei","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_87","first-page":"1070","article-title":"Analysis of three Chinese pedigrees affected with recurrent hydatidiform mole due to variants of the NLRP7 gene","volume":"39","author":"Shen","year":"2022","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/332459a0","article-title":"Human gene expression first occurs between the four- and eight-cell stages of preimplantation development","volume":"332","author":"Braude","year":"1988","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1242\/dev.064741","article-title":"Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development","volume":"138","author":"Vassena","year":"2011","journal-title":"Development"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1146\/annurev-cellbio-100913-013027","article-title":"Zygotic genome activation during the maternal-to-zygotic transition","volume":"30","author":"Lee","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s13577-025-01346-0","article-title":"Generation and characterization of human iPSC lines from two familial recurrent hydatidiform mole patients carrying homozygous mutations in the NLRP7 gene","volume":"39","author":"Cai","year":"2026","journal-title":"Hum. Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1399-0004.2009.01189.x","article-title":"A strong founder effect for two NLRP7 mutations in the Indian population: An intriguing observation","volume":"76","author":"Slim","year":"2009","journal-title":"Clin. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1136\/jmedgenet-2014-102546","article-title":"Comprehensive genotype-phenotype correlations between NLRP7 mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation","volume":"51","author":"Nguyen","year":"2014","journal-title":"J. Med. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1007\/s10815-020-01861-z","article-title":"Pregnancy after oocyte donation in a patient with NLRP7 gene mutations and recurrent molar hydatidiform pregnancies","volume":"37","author":"Cozette","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1007\/s10815-021-02325-8","article-title":"Application of next-generation sequencing to preimplantation genetic testing for recurrent hydatidiform mole patients","volume":"38","author":"Yang","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/ijgo.12615","article-title":"Update on the diagnosis and management of gestational trophoblastic disease","volume":"143","author":"Ngan","year":"2018","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/ijgo.70275","article-title":"Diagnosis and management of gestational trophoblastic disease: 2025 update","volume":"171","author":"Ngan","year":"2025","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"102890","DOI":"10.1016\/j.eclinm.2024.102890","article-title":"Prognosticating gestational trophoblastic neoplasia: From FIGO 2000 to future models","volume":"77","author":"Lin","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1200\/JCO.2002.07.166","article-title":"Low-risk persistent gestational trophoblastic disease: Outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000","volume":"20","author":"McNeish","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1200\/JCO.2012.43.1817","article-title":"EMA\/CO for high-risk gestational trophoblastic neoplasia: Good outcomes with induction low-dose etoposide-cisplatin and genetic analysis","volume":"31","author":"Alifrangis","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nrc.2017.7","article-title":"Liquid biopsies come of age: Towards implementation of circulating tumour DNA","volume":"17","author":"Wan","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.stemcr.2018.07.004","article-title":"Self-renewing trophoblast organoids recapitulate the developmental program of the early human placenta","volume":"11","author":"Haider","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41586-018-0753-3","article-title":"Trophoblast organoids as a model for maternal-fetal interactions during human placentation","volume":"564","author":"Turco","year":"2018","journal-title":"Nature"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2386\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:46:19Z","timestamp":1784879179000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":103,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18152386"],"URL":"https:\/\/doi.org\/10.3390\/cancers18152386","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}