{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:17:11Z","timestamp":1791908231938,"version":"4.3.4"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Oxidative stress and metabolic disorders significantly contribute to the development of polycystic ovarian syndrome (PCOS). Heme oxygenase-1 (HMOX1) plays a key role in the degradation of heme and the regulation of oxidative stress, ferroptosis, and glycolipid metabolism. This study explored the relationship between\n                      <jats:italic>HMOX1<\/jats:italic>\n                      promoter T-413A single nucleotide polymorphism (SNP, rs2071746), (GT)n dinucleotide repeat variant (rs3074372), plasma HMOX1 levels, and the risk of PCOS in Chinese women.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This case-control study included 1092 women diagnosed with PCOS and 805 controls. The (GT)n and rs2071746 polymorphisms were identified using polymerase chain reaction amplification, followed by capillary electrophoresis or restriction fragment length polymorphism. HMOX1 levels and clinical, metabolic, hormonal, and oxidative stress indices were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>HOMX1<\/jats:italic>\n                      rs2071746T\/A SNP was associated with an increased risk of PCOS based on genotype, recessive, dominant, and allele genetic models (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). After adjusting for age, body mass index, and recruitment year of participants, the dominant model (odds ratio [OR] = 1.272, 95% confidence interval [CI]: 1.013\u20131.597,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.039) and the TT genotype (OR\u00a0=\u00a01.395, 95% CI: 1.033\u20131.883,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.030, with the AA genotype as the reference) remained a significant predictor of PCOS in the logistic regression models. No significant differences were observed in the (GT)n polymorphism of\n                      <jats:italic>HMOX1<\/jats:italic>\n                      based on different genetic models. However, the TT\/SS combined genotype of\n                      <jats:italic>HMOX1<\/jats:italic>\n                      rs2071746T\/A and (GT)n polymorphisms was associated with an increased risk of PCOS (OR\u00a0=\u00a01.442, 95% CI: 1.021\u20132.035,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.037). Furthermore, elevated HMOX1 levels were related to a slight but significant increase in the risk of PCOS, and the rs2071746T\/A and (GT)n genetic variants significantly affected obesity, oxidative stress, endocrine abnormalities, and metabolic disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>HMOX1<\/jats:italic>\n                      rs2071746T\/A variant and elevated plasma HMOX1 levels are associated with an increased risk of PCOS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1644373","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T05:22:33Z","timestamp":1762233753000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The promoter T-413A variant and elevated enzyme levels of heme oxygenase-1 associated with an increased risk of polycystic ovarian syndrome"],"prefix":"10.3389","volume":"16","author":[{"given":"Qiuyi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiagui","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai","family":"Bai","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"Department of Reproductive Medical Center, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Fan","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.07.025","article-title":"Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"120","author":"Teede","year":"2023","journal-title":"Fertil Steril"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2018.24","article-title":"Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment","volume":"14","author":"Escobar-Morreale","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1358755","article-title":"PCOS stratification for precision diagnostics and treatment","volume":"12","author":"Joshi","year":"2024","journal-title":"Front Cell Dev Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.3390\/biomedicines13081912","article-title":"PCOS and the genome: is the genetic puzzle still worth solving","volume":"13","author":"Palumbo","year":"2025","journal-title":"Biomedicines"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e230463","DOI":"10.1530\/EC-23-0463","article-title":"Heme oxygenase 2 genetic variants alter hormonal and metabolic traits in polycystic ovary syndrome","volume":"13","author":"Zhang","year":"2024","journal-title":"Endocr Connect"},{"key":"B6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.fertnstert.2016.05.011","article-title":"Yang D Environmental determinants of polycystic ovary syndrome","volume":"106","author":"Merkin","year":"2016","journal-title":"Fertil Steril"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249698","article-title":"Tosaki A heme degradation in pathophysiology of and countermeasures to inflammation-associated disease","volume":"21","author":"Haines","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8100475","article-title":"Kozlov AV role of heme oxygenase as a modulator of heme-mediated pathways","volume":"8","author":"Duvigneau","year":"2019","journal-title":"Antioxidants (Basel)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3153","article-title":"Heme oxygenase in the regulation of vascular biology: from molecular mechanisms to therapeutic opportunities","volume":"14","author":"Kim","year":"2011","journal-title":"Antioxid Redox Signal"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00023","article-title":"Mann GE heme oxygenase dependent bilirubin generation in vascular cells: A role in preventing endothelial dysfunction in local tissue microenvironment","volume":"11","author":"Nitti","year":"2020","journal-title":"Front Physiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3892\/mmr.2021.12545","article-title":"Jin YL Association between HO\u22121 gene promoter polymorphisms and diseases (Review)","volume":"25","author":"Ma","year":"2022","journal-title":"Mol Med Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01110113","article-title":"Tarng DC Length polymorphism in heme oxygenase-1 and cardiovascular events and mortality in hemodialysis patients","volume":"8","author":"Chen","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s40200-025-01575-y","article-title":"Association between microsatellite polymorphism in the Heme Oxygenase-1 (HMOX1) gene promoter and type 2 diabetes: an updated meta-analysis","volume":"24","author":"Rivera-Valdes","year":"2025","journal-title":"J Diabetes Metab Disord"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03337","article-title":"Microsatellite polymorphism in the heme oxygenase-1 promoter is associated with nonsevere and late-onset preeclampsia","volume":"64","author":"Kaartokallio","year":"2014","journal-title":"Hypertension"},{"key":"B15","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1111\/jcmm.13028","article-title":"Li Y Genetic polymorphism of heme oxygenase 1 promoter in the occurrence and severity of chronic obstructive pulmonary disease: a meta-analysis","volume":"21","author":"Zhou","year":"2017","journal-title":"J Cell Mol Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1215246","article-title":"Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis","volume":"10","author":"Roy-Vallejo","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12974-018-1102-z","article-title":"Heme oxygenase-1 promoter region (GT)n polymorphism associates with increased neuroimmune activation and risk for encephalitis in HIV infection","volume":"15","author":"Gill","year":"2018","journal-title":"J Neuroinflammation"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-024-03726-2","article-title":"Increased oxidative stress is associated with hyperandrogenemia in polycystic ovary syndrome evidenced by oxidized lipoproteins stimulating rat ovarian androgen synthesis in vitro","volume":"84","author":"Zhang","year":"2024","journal-title":"Endocrine"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084110","article-title":"Controversies in the pathogenesis, diagnosis and treatment of PCOS: focus on insulin resistance, inflammation, and hyperandrogenism","volume":"23","author":"Armanini","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2021.07.1203","article-title":"Oxidative stress promotes hyperandrogenism by reducing sex hormone-binding globulin in polycystic ovary syndrome","volume":"116","author":"Sun","year":"2021","journal-title":"Fertil Steril"},{"key":"B21","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1111\/cen.13171","article-title":"Oxidative stress status in Chinese women with different clinical phenotypes of polycystic ovary syndrome","volume":"86","author":"Zhang","year":"2017","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0293447","DOI":"10.1371\/journal.pone.0293447","article-title":"Screening of potential biomarkers for polycystic ovary syndrome and identification of expression and immune characteristics","volume":"18","author":"Liu","year":"2023","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4161\/adip.28731","article-title":"Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age, body weight, and body mass index","volume":"3","author":"Manneras-Holm","year":"2014","journal-title":"Adipocyte"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu029","article-title":"Association of heme oxygenase-1 with the risk of polycystic ovary syndrome in non-obese women","volume":"29","author":"Gao","year":"2014","journal-title":"Hum Reprod"},{"key":"B25","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","year":"2004","journal-title":"Fertil Steril"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-018-0999-5","article-title":"Association of SOD2 A16V and PON2 S311C polymorphisms with polycystic ovary syndrome in Chinese women","volume":"42","author":"Liu","year":"2019","journal-title":"J Endocrinol Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.02.024","article-title":"Antioxidant properties of high-density lipoproteins are impaired in women with polycystic ovary syndrome","volume":"103","author":"Zhang","year":"2015","journal-title":"Fertil Steril"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des191","article-title":"and B levels, dyslipidemia and metabolic syndrome in south-west Chinese women with PCOS","volume":"27","author":"Zhang","year":"2012","journal-title":"Hum Reprod"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)57728-0","article-title":"Ultrasound assessment of ovarian stroma hypertrophy in hyperandrogenism and ovulation disorders: visual analysis versus computerized quantification","volume":"64","author":"Robert","year":"1995","journal-title":"Fertil Steril"},{"key":"B30","first-page":"36","article-title":"PCR technology","volume-title":"Principles and applications for DNA amplification","author":"Higuchi","year":"1989"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2011.76","article-title":"Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African-Americans","volume":"13","author":"Seu","year":"2012","journal-title":"Genes Immun"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1016\/j.fertnstert.2011.01.038","article-title":"Role of androgen-mediated enhancement of erythropoiesis in the increased body iron stores of patients with polycystic ovary syndrome","volume":"95","author":"Escobar-Morreale","year":"2011","journal-title":"Fertil Steril"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11030555","article-title":"Heme oxygenase-1: an anti-inflammatory effector in cardiovascular, lung, and related metabolic disorders","volume":"11","author":"Ryter","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107975","article-title":"Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications","volume":"231","author":"McClung","year":"2022","journal-title":"Pharmacol Ther"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.702974","article-title":"Heme oxygenase-1 at the nexus of endothelial cell fate decision under oxidative stress","volume":"9","author":"Raghunandan","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012371","article-title":"Plasma heme oxygenase-1 concentration is elevated in individuals with type 2 diabetes mellitus","volume":"5","author":"Bao","year":"2010","journal-title":"PloS One"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7176","article-title":"The roles of NRF2 in modulating cellular iron homeostasis","volume":"29","author":"Kerins","year":"2018","journal-title":"Antioxid Redox Signal"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2211","article-title":"Role of decreased circulating hepcidin concentrations in the iron excess of women with the polycystic ovary syndrome","volume":"96","author":"Luque-Ramirez","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"B39","doi-asserted-by":"publisher","first-page":"7","DOI":"10.15430\/JCP.2022.27.1.7","article-title":"Non-canonical vs. Canonical functions of heme oxygenase-1 in cancer","volume":"27","author":"Jagadeesh","year":"2022","journal-title":"J Cancer Prev"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-1007-9","article-title":"14-3-3zeta inhibits heme oxygenase-1 (HO-1) degradation and promotes hepatocellular carcinoma proliferation: involvement of STAT3 signaling","volume":"38","author":"Song","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.028001","article-title":"Oligomerization is crucial for the stability and function of heme oxygenase-1 in the endoplasmic reticulum","volume":"284","author":"Hwang","year":"2009","journal-title":"J Biol Chem"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M607954200","article-title":"Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress","volume":"282","author":"Lin","year":"2007","journal-title":"J Biol Chem"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.294","article-title":"Acetylation is essential for nuclear heme oxygenase-1-enhanced tumor growth and invasiveness","volume":"36","author":"Hsu","year":"2017","journal-title":"Oncogene"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.244","article-title":"TRC8 suppresses tumorigenesis through targeting heme oxygenase-1 for ubiquitination and degradation","volume":"32","author":"Lin","year":"2013","journal-title":"Oncogene"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.10.077","article-title":"Protein kinase Akt\/PKB phosphorylates heme oxygenase-1 in vitro and in vivo","volume":"578","author":"Salinas","year":"2004","journal-title":"FEBS Lett"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000001161","article-title":"Study of the influence of heme oxygenase 1 gene single nucleotide polymorphism (rs2071746) on esophageal varices among patients with cirrhosis","volume":"30","author":"Ellakany","year":"2018","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200308000-00013","article-title":"Association of a promoter variant of the haeme oxygenase-1 gene with hypertension in women","volume":"21","author":"Ono","year":"2003","journal-title":"J Hypertens"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2003.11.021","article-title":"A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese","volume":"173","author":"Ono","year":"2004","journal-title":"Atherosclerosis"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e1825","DOI":"10.1097\/MD.0000000000001825","article-title":"Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes: A case-control study","volume":"94","author":"Lee","year":"2015","journal-title":"Med (Baltimore)"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/art.23048","article-title":"HO-1 promoter polymorphism associated with rheumatoid arthritis","volume":"56","author":"Rueda","year":"2007","journal-title":"Arthritis Rheumatol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21937","article-title":"A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with risk for melanoma","volume":"119","author":"Okamoto","year":"2006","journal-title":"Int J Cancer"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.08.047","article-title":"Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals","volume":"219","author":"Wu","year":"2011","journal-title":"Atherosclerosis"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e77224","DOI":"10.1371\/journal.pone.0077224","article-title":"Alternative 5' untranslated regions are involved in expression regulation of human heme oxygenase-1","volume":"8","author":"Kramer","year":"2013","journal-title":"PloS One"}],"updated-by":[{"DOI":"10.3389\/fendo.2026.1739810","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000}}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1644373\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:40:26Z","timestamp":1771911626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1644373\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":53,"alternative-id":["10.3389\/fendo.2025.1644373"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1644373","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"article-number":"1644373"}}