{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T13:44:04Z","timestamp":1786455844981,"version":"build-2736575974"},"reference-count":115,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The reduction in oocyte competence and ovarian reserve coincides with reproductive ageing; nevertheless, the molecular mechanisms underlying this phenomenon remain poorly understood. Our testable mechanistic hypothesis is that the oxidative stress\u2013telomere axis is a crucial regulatory mechanism controlling meiotic stability, mitochondrial resilience, and granulosa cell integrity. This notion posits that granulosa and cumulus cells have accelerated telomere attrition and impaired DNA-damage responses due to elevated amounts of reactive oxygen species, which also induce oxidative guanine lesions, inhibit telomerase function, and generate telomeric replication stress. This telomere-dependent vulnerability is anticipated to compromise developmental competence, disrupt meiotic spindle integrity, and diminish metabolic support to the oocyte, prior to observable declines in AMH or follicle count. Data from human IVF cohorts supports the model: Conditions such as PCOS, endometriosis, and POI have unique oxidative-telomeric profiles, whereas diminished telomere length in granulosa cells, reduced telomerase activity, and worse fertilisation, blastulation, and pregnancy outcomes are associated with increased follicular oxidative DNA damage. The findings suggest that oxidative DNA damage (8-OHdG), telomerase activity, and the structure of granulosa-cell telomeres may serve as preliminary indicators of preclinical ovarian ageing. This theory may be directly evaluated in forthcoming longitudinal studies and specific treatments related to telomerase regulation, mitochondrial medicines, or redox modulation. Consequently, the oxidative stress\u2013telomere axis may represent a vital physiologic factor affecting reproductive lifespan and a prospective target for personalised ART techniques.<\/jats:p>","DOI":"10.3390\/ijms262311359","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T14:59:04Z","timestamp":1763996344000},"page":"11359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Oxidative Stress\u2013Telomere Axis in IVF: Molecular Mechanisms, Biomarkers, and Clinical Translation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-7619","authenticated-orcid":false,"given":"Charalampos","family":"Voros","sequence":"first","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios","family":"Chatzinikolaou","sequence":"additional","affiliation":[{"name":"Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Papadimas","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Polykalas","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7760-0608","authenticated-orcid":false,"given":"Ioakeim","family":"Sapantzoglou","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristotelis-Marios","family":"Koulakmanidis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diamantis","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"IVF Athens Reproduction Center, 15123 Maroussi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Kanaka","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kanaka","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7563-4305","authenticated-orcid":false,"given":"Kyriakos","family":"Bananis","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospitals NHS Foundation Trust, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"IVF Athens Reproduction Center, 15123 Maroussi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"IVF Athens Reproduction Center, 15123 Maroussi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-5054","authenticated-orcid":false,"given":"Ioannis","family":"Papapanagiotou","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalampos","family":"Tsimpoukelis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Anastasia","family":"Daskalaki","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-7796","authenticated-orcid":false,"given":"Marianna","family":"Theodora","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Thomakos","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-5922","authenticated-orcid":false,"given":"Panagiotis","family":"Antsaklis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8686-594X","authenticated-orcid":false,"given":"Dimitrios","family":"Loutradis","sequence":"additional","affiliation":[{"name":"Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Fertility Institute-Assisted Reproduction Unit, Paster 15, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-211X","authenticated-orcid":false,"given":"Georgios","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13048-023-01151-z","article-title":"Mechanisms of ovarian aging in women: A review","volume":"16","author":"Wang","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.fertnstert.2013.12.032","article-title":"Female age-related fertility decline","volume":"101","author":"No","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.fertnstert.2025.05.150","article-title":"Advanced maternal age was associated with an annual decline in reproductive success despite use of donor oocytes: A retrospective study","volume":"124","author":"Sanz","year":"2025","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.2147\/RMHP.S517401","article-title":"The Impact of Social, Cultural, and Identity-Related Factors on Delayed Childbearing: A Multi-Center Study","volume":"18","author":"Lei","year":"2025","journal-title":"Risk Manag. Healthc. Policy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4103\/1735-1995.193172","article-title":"Assessment of ovarian reserve: Anti-Mullerian hormone versus follicle stimulating hormone","volume":"21","author":"Jamil","year":"2016","journal-title":"J. Res. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Voros, C., Athanasiou, D., Papapanagiotou, I., Mavrogianni, D., Varthaliti, A., Bananis, K., Athanasiou, A., Athanasiou, A., Papadimas, G., and Gkirgkinoudis, A. (2025). Cracking the Code of Oocyte Quality: The Oxidative Stress Link to IVF Success. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136377"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrm2848","article-title":"Telomeres: Protecting chromosomes against genome instability","volume":"11","author":"Karlseder","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ebiom.2017.03.027","article-title":"Telomeres and Cell Senescence\u2014Size Matters Not","volume":"21","author":"Victorelli","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"032","DOI":"10.1055\/s-0028-1108008","article-title":"Mouse Oocyte Control of Granulosa Cell Development and Function: Paracrine Regulation of Cumulus Cell Metabolism","volume":"27","author":"Su","year":"2009","journal-title":"Semin. Reprod. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kordowitzki, P. (2021). Oxidative Stress Induces Telomere Dysfunction and Shortening in Human Oocytes of Advanced Age Donors. Cells, 10.","DOI":"10.3390\/cells10081866"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41556-022-00842-x","article-title":"Telomere dysfunction in ageing and age-related diseases","volume":"24","author":"Rossiello","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s13048-023-01211-4","article-title":"Potential effects of assisted reproductive technology on telomere length and telomerase activity in human oocytes and early embryos","volume":"16","author":"Tire","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s10815-011-9600-2","article-title":"Women with high telomerase activity in luteinised granulosa cells have a higher pregnancy rate during in vitro fertilisation treatment","volume":"28","author":"Chen","year":"2011","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ju, W., Zhao, Y., Yu, Y., Zhao, S., Xiang, S., and Lian, F. (2024). Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1361289"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13048-022-01032-x","article-title":"The role of oxidative stress in ovarian aging: A review","volume":"15","author":"Yan","year":"2022","journal-title":"J. Ovarian Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hajam, Y.A., Rani, R., Ganie, S.Y., Sheikh, T.A., Javaid, D., Qadri, S.S., Pramodh, S., Alsulimani, A., Alkhanani, M.F., and Harakeh, S. (2022). Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells, 11.","DOI":"10.3390\/cells11030552"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mad.2018.03.013","article-title":"The impact of oxidative DNA damage and stress on telomere homeostasis","volume":"177","author":"Barnes","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Turathum, B., Gao, E.M., and Chian, R.C. (2021). The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization. Cells, 10.","DOI":"10.3390\/cells10092292"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Moustakli, E., Stavros, S., Katopodis, P., Skentou, C., Potiris, A., Panagopoulos, P., Domali, E., Arkoulis, I., Karampitsakos, T., and Sarafi, E. (2025). Oxidative Stress and the NLRP3 Inflammasome: Focus on Female Fertility and Reproductive Health. Cells, 14.","DOI":"10.3390\/cells14010036"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zeber-Lubecka, N., Ciebiera, M., and Hennig, E.E. (2023). Polycystic Ovary Syndrome and Oxidative Stress\u2014From Bench to Bedside. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814126"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Coluzzi, E., Leone, S., and Sgura, A. (2019). Oxidative Stress Induces Telomere Dysfunction and Senescence by Replication Fork Arrest. Cells, 8.","DOI":"10.3390\/cells8010019"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tamura, H., Jozaki, M., Tanabe, M., Shirafuta, Y., Mihara, Y., Shinagawa, M., Tamura, I., Maekawa, R., Sato, S., and Taketani, T. (2020). Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031135"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1186\/s12967-025-06966-6","article-title":"Mitochondria-driven inflammation: A new frontier in ovarian ageing","volume":"23","author":"Ju","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.33549\/physiolres.934233","article-title":"Metabolic Cooperation in the Ovarian Follicle","volume":"69","author":"Fontana","year":"2020","journal-title":"Physiol Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"B\u00f3dis, J., Sulyok, E., V\u00e1rnagy, \u00c1., Pr\u00e9musz, V., G\u00f6d\u00f6ny, K., Makai, A., Szenczi, \u00c1., and Varjas, T. (2021). Expression of mRNAs for pro-and anti-apoptotic factors in granulosa cells and follicular fluid of women undergoing in vitro fertilization. A pilot study. BMC Pregnancy Childbirth, 21.","DOI":"10.1186\/s12884-021-03834-1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nature09787","article-title":"Telomere dysfunction induces metabolic and mitochondrial compromise","volume":"470","author":"Sahin","year":"2011","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lin, X., Dai, Y., Tong, X., Xu, W., Huang, Q., Jin, X., Li, C., Zhou, F., Zhou, H., and Lin, X. (2020). Excessive oxidative stress in cumulus granulosa cells induced cell senescence contributes to endometriosis-associated infertility. Redox Biol., 30.","DOI":"10.1016\/j.redox.2020.101431"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Vollenhoven, B., and Hunt, S. (2018). Ovarian ageing and the impact on female fertility. F1000Research, 7.","DOI":"10.12688\/f1000research.16509.1"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pa\u0144czyszyn, A., Boniewska-Bernacka, E., Wertel, I., Sadakierska-Chudy, A., and Goc, A. (2024). Telomeres and SIRT1 as Biomarkers of Gamete Oxidative Stress, Fertility, and Potential IVF Outcome. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168652"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13048-020-00702-y","article-title":"Telomere length in granulosa cells and leukocytes: A potential marker of female fertility? A systematic review of the literature","volume":"13","author":"Fattet","year":"2020","journal-title":"J. Ovarian Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41580-021-00328-y","article-title":"Shaping human telomeres: From shelterin and CST complexes to telomeric chromatin organization","volume":"22","author":"Lim","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.diff.2017.12.002","article-title":"Impact of oxidative stress on telomere biology","volume":"99","author":"Ahmed","year":"2018","journal-title":"Differentiation"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, H. (2025). The role of granulosa cells in oocyte development and aging: Mechanisms and therapeutic opportunities. Semin. Cell Dev. Biol., 171.","DOI":"10.1016\/j.semcdb.2025.103614"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.fertnstert.2014.11.015","article-title":"Oocyte environment: Follicular fluid and cumulus cells are critical for oocyte health","volume":"103","author":"Dumesic","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"He, M., Zhang, T., Yang, Y., and Wang, C. (2021). Mechanisms of Oocyte Maturation and Related Epigenetic Regulation. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.654028"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cimadomo, D., Fabozzi, G., Vaiarelli, A., Ubaldi, N., Ubaldi, F.M., and Rienzi, L. (2018). Impact of Maternal Age on Oocyte and Embryo Competence. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00327"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Toupance, S., Fattet, A.J., Thornton, S.N., Benetos, A., Gu\u00e9ant, J.L., and Koscinski, I. (2021). Ovarian Telomerase and Female Fertility. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070842"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1093\/humrep\/deab201","article-title":"Preconception leukocyte telomere length and pregnancy outcomes among women with demonstrated fecundity","volume":"36","author":"Kim","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.3892\/mmr.2020.11274","article-title":"Telomerase and telomeres in aging theory and chronographic aging theory (Review)","volume":"22","author":"Razgonova","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Panasiak, L., Kuci\u0144ski, M., Hliwa, P., Pomianowski, K., and Ocalewicz, K. (2023). Telomerase Activity in Somatic Tissues and Ovaries of Diploid and Triploid Rainbow Trout (Oncorhynchus mykiss) Females. Cells, 12.","DOI":"10.3390\/cells12131772"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"P\u00e9ntek, S., V\u00e1rnagy, \u00c1., Farkas, B., Mauchart, P., G\u00f6d\u00f6ny, K., Varjas, T., K\u0151szegi, T., Kaltenecker, P., Jakabfi-Csepregi, R., and Kov\u00e1cs, K. (2023). Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization. Antioxidants, 12.","DOI":"10.3390\/antiox12020419"},{"key":"ref_42","first-page":"24","article-title":"Telomere length and telomerase activity in men and non-pregnant women with and without metabolic syndrome: A systematic review and bootstrapped meta-analysis","volume":"24","author":"Varikasuvu","year":"2025","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3892\/mmr.2016.5231","article-title":"Telomerase activity in pregnancy complications (Review)","volume":"14","author":"Fragkiadaki","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Moustakli, E., Grigoriadis, T., Stavros, S., Potiris, A., Zikopoulos, A., Gerede, A., Tsimpoukis, I., Papageorgiou, C., Louis, K., and Domali, E. (2025). Artificial Intelligence in Assessing Reproductive Aging: Role of Mitochondria, Oxidative Stress, and Telomere Biology. Diagnostics, 15.","DOI":"10.3390\/diagnostics15162075"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s12967-025-06223-w","article-title":"The impact of mitochondrial dysfunction on ovarian aging","volume":"23","author":"Zhang","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fertnstert.2023.10.027","article-title":"Telomere Length: A Marker Reprod. Aging?","volume":"121","author":"Pirtea","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.fertnstert.2014.10.021","article-title":"Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests","volume":"102","author":"Wang","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s10815-018-1143-3","article-title":"Influence of follicular fluid and cumulus cells on oocyte quality: Clinical implications","volume":"35","author":"Giorgi","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jiang, S., Jiang, X., Li, D., Lyu, Q., and Li, W. (2025). Telomere length of granulosa cells is positively associated with oocyte maturation and fertilization. Reprod. Biomed. Online, 50.","DOI":"10.1016\/j.rbmo.2025.104803"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Michaeli, J., Smoom, R., Serruya, N., El Ayoubi, H., Rotshenker-Olshinka, K., Srebnik, N., Michaeli, O., Eldar-Geva, T., and Tzfati, Y. (2022). Leukocyte Telomere Length Correlates with Extended Female Fertility. Cells, 11.","DOI":"10.3390\/cells11030513"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.fertnstert.2023.11.011","article-title":"Leukocyte telomere length and DNA methylome as biomarkers of ovarian reserve and embryo aneuploidy: The intricate relationship between somatic and reproductive aging","volume":"121","author":"Garg","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/NNR.0000000000000037","article-title":"Telomere Length: A Review of Methods for Measurement","volume":"63","author":"Montpetit","year":"2014","journal-title":"Nurs. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Axelrad, M.D., Budagov, T., and Atzmon, G. (2013). Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence. J. Vis. Exp. JoVE, e50246.","DOI":"10.3791\/50246"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1101\/gad.1807009","article-title":"Calorie restriction and the exercise of chromatin","volume":"23","author":"Vaquero","year":"2009","journal-title":"Genes Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"113656","DOI":"10.1016\/j.celrep.2023.113656","article-title":"Oxidative guanine base damage plays a dual role in regulating productive ALT-associated homology-directed repair","volume":"43","author":"Thosar","year":"2024","journal-title":"Cell Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lamsira, H.K., Pelligrini, L., Bertani, N., Maresca, L., Galliano, D., Pellicer, A., Valensise, H., Klinger, F.G., and Cozzolino, M. (2024). O-253 Altered telomerase activity in ovarian follicular Cells in patients with polycystic ovary syndrome. Hum. Reprod., 39.","DOI":"10.1093\/humrep\/deae108.300"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yan, H., Wang, L., Zhang, G., Li, N., Zhao, Y., Liu, J., Jiang, M., Du, X., Zeng, Q., and Xiong, D. (2024). Oxidative stress and energy metabolism abnormalities in polycystic ovary syndrome: From mechanisms to therapeutic strategies. Reprod. Biol. Endocrinol., 22.","DOI":"10.1186\/s12958-024-01337-0"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e31383","DOI":"10.1002\/jcp.31383","article-title":"Melatonin regulates endoplasmic reticulum stress in diverse pathophysiological contexts: A comprehensive mechanistic review","volume":"239","author":"Chuffa","year":"2024","journal-title":"J. Cell. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Limonad, O., Hantisteanu, S., Sharon, S.M., Haggiag, N., Estrada, D., Michaeli, M., and Shalom-Paz, E. (2021). P\u2013565 Does length really matter? The impact of lifestyle on granulosa cell telomeres length and IVF outcome. Hum. Reprod., 36.","DOI":"10.1093\/humrep\/deab130.564"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Huang, Q.Y., Chen, S.R., Chen, J.M., Shi, Q.Y., and Lin, S. (2022). Therapeutic options for premature ovarian insufficiency: An updated review. Reprod. Biol. Endocrinol., 20, Erratum in Reprod. Biol. Endocrinol. 2023, 21, 81.","DOI":"10.1186\/s12958-022-00892-8"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"109011","DOI":"10.1016\/j.reprotox.2025.109011","article-title":"Oxidative stress: Oocyte quality and infertility","volume":"137","author":"Begum","year":"2025","journal-title":"Reprod. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Colella, M., Cuomo, D., Peluso, T., Falanga, I., Mallardo, M., De Felice, M., and Ambrosino, C. (2021). Ovarian Aging: Role of Pituitary-Ovarian Axis Hormones and ncRNAs in Regulating Ovarian Mitochondrial Activity. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.791071"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative Stress and Antioxidant Defense","volume":"5","author":"Birben","year":"2012","journal-title":"World Allergy Organ. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e70017","DOI":"10.1002\/dvg.70017","article-title":"A Comprehensive Review of Mitochondrial Complex I During Mammalian Oocyte Maturation","volume":"63","author":"Bozdemir","year":"2025","journal-title":"Genesis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1071\/RD9900153","article-title":"Steroidogenic cytochrome P450 enzymes and ovarian steroidogenesis. Reproduction, Fertility and Development","volume":"2","author":"Rodgers","year":"1990","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"104003","DOI":"10.1016\/j.psj.2024.104003","article-title":"Oxidative stress in poultry production","volume":"103","author":"Oke","year":"2024","journal-title":"Poult. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Yang, J., Luo, J., Tian, X., Zhao, Y., Li, Y., and Wu, X. (2024). Progress in Understanding Oxidative Stress, Aging, and Aging-Related Diseases. Antioxidants, 13.","DOI":"10.3390\/antiox13040394"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Revelli, A., Piane, L.D., Casano, S., Molinari, E., Massobrio, M., and Rinaudo, P. (2009). Follicular fluid content and oocyte quality: From single biochemical markers to metabolomics. Reprod. Biol. Endocrinol., 7.","DOI":"10.1186\/1477-7827-7-40"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Chen, Y., Yang, J., and Zhang, L. (2023). The Impact of Follicular Fluid Oxidative Stress Levels on the Outcomes of Assisted Reproductive Therapy. Antioxidants, 12.","DOI":"10.3390\/antiox12122117"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10815-020-02014-y","article-title":"Oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome correlate with a decrease in embryo quality","volume":"38","author":"Liu","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhang, Y., Li, T., Ren, Y., Zhou, P., Fu, L., Xiao, C., Huang, Z., Huang, H., and Xie, W. (2025). Transcriptional insights on the incomplete cytoplasmic maturation and developmental potential of oocytes cultured without granulosa cells in mice. BMC Genom., 26, Erratum in BMC Genom. 2025, 26, 572.","DOI":"10.1186\/s12864-025-11455-7"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Liu, H., Jin, L., Wang, X., Shi, J., He, Y., Sun, N., and Yang, F. (2025). Reactive oxygen species in polycystic ovary syndrome: Mechanistic insights into pathogenesis and therapeutic opportunities. Redox Biol., 85.","DOI":"10.1016\/j.redox.2025.103776"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Artini, P.G., Scarf\u00f2, G., Marzi, I., Fusi, J., Obino, M.E., Franzoni, F., Zappelli, E., Chelucci, E., Martini, C., and Cela, V. (2022). Oxidative Stress-Related Signaling Pathways Predict Oocytes\u2019 Fertilization In Vitro and Embryo Quality. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113442"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S80","DOI":"10.1016\/j.fertnstert.2011.07.309","article-title":"Evaluation of follicular fluid antioxidant-oxidant status in high, normo, and poor responder patients undergoing assisted reproductive techniques","volume":"96","author":"Karakaya","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kirillova, A., Smitz, J.E.J., Sukhikh, G.T., and Mazunin, I. (2021). The Role of Mitochondria in Oocyte Maturation. Cells, 10.","DOI":"10.3390\/cells10092484"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Song, J., Xiao, L., Zhang, Z., Wang, Y., Kouis, P., Rasmussen, L.J., and Dai, F. (2024). Effects of reactive oxygen species and mitochondrial dysfunction on reproductive aging. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1347286"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41594-022-00790-y","article-title":"Telomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening","volume":"29","author":"Barnes","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Vaiserman, A., and Krasnienkov, D. (2021). Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.630186"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"gaae015","DOI":"10.1093\/molehr\/gaae015","article-title":"Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome","volume":"30","author":"Tanaka","year":"2024","journal-title":"Mol. Hum. Reprod."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e13836","DOI":"10.1111\/acel.13836","article-title":"Canonical and extra-telomeric functions of telomerase: Implications for healthy ageing conferred by endurance training","volume":"22","author":"Denham","year":"2023","journal-title":"Aging Cell."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ghazi, A., and Henry, H. (2025). Reproductive Fitness and the Links to Chronic Disease and Systemic Aging. Physiology.","DOI":"10.1152\/physiol.00013.2025"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1186\/s13287-020-01948-5","article-title":"Melatonin suppresses ER stress-dependent proapoptotic effects via AMPK in bone mesenchymal stem cells during mitochondrial oxidative damage","volume":"11","author":"Fan","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Dabravolski, S.A., Nikiforov, N.G., Eid, A.H., Nedosugova, L.V., Starodubova, A.V., Popkova, T.V., Bezsonov, E.E., and Orekhov, A.N. (2021). Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083923"},{"key":"ref_84","first-page":"e66128","article-title":"Endometriosis: A Comprehensive Exploration of Inflammatory Mechanisms and Fertility Implications","volume":"16","author":"Rathod","year":"2024","journal-title":"Cureus"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1089\/ars.2019.7984","article-title":"Redox Biology of Human Cumulus Cells: Basic Concepts, Impact on Oocyte Quality, and Potential Clinical Use","volume":"32","author":"Klamt","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.crphys.2021.03.002","article-title":"Interplay between oxidative stress, SIRT1, reproductive and metabolic functions","volume":"4","author":"Alam","year":"2021","journal-title":"Curr. Res. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"13736","DOI":"10.1073\/pnas.1001399107","article-title":"Sirtuin 1 regulation of developmental genes during differentiation of stem cells","volume":"107","author":"Calvanese","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1517\/14728222.2012.648926","article-title":"SIRT1: New avenues of discovery for disorders of oxidative stress","volume":"16","author":"Chong","year":"2012","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.3390\/cimb45030133","article-title":"Regulation of SIRT1 in Ovarian Function: PCOS Treatment","volume":"45","author":"Li","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Zhang, H., Lin, F., Zhao, J., and Wang, Z. (2020). Expression Regulation and Physiological Role of Transcription Factor FOXO3a During Ovarian Follicular Development. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.595086"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1038\/ncomms2861","article-title":"Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice","volume":"4","author":"Pelosi","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Gao, X., Wang, B., Huang, Y., Wu, M., Li, Y., Li, Y., Zhu, X., and Wu, M. (2023). Role of the Nrf2 Signaling Pathway in Ovarian Aging: Potential Mechanism and Protective Strategies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713327"},{"key":"ref_93","first-page":"450","article-title":"AMP-activated protein kinase signaling in metabolic regulation","volume":"39","author":"Long","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2373742","DOI":"10.1080\/09513590.2024.2373742","article-title":"Telomerase activity, telomere length, and the euploidy rate of human embryos","volume":"40","author":"Longo","year":"2024","journal-title":"Gynecol. Endocrinol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sk\u00e5ra, K.H., Lee, Y., Jugessur, A., Gjessing, H.K., Aviv, A., Brumpton, B., N\u00e6ss, \u00d8., Hern\u00e1ez, \u00c1., Hanevik, H.I., and Magnus, P. (2024). Telomere length in relation to fecundability and use of assisted reproductive technologies: The Norwegian Mother, Father, and Child Cohort Study. BMC Med., 22.","DOI":"10.1186\/s12916-024-03795-0"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/s12291-023-01139-y","article-title":"Role of the AMP-Activated Protein Kinase in the Pathogenesis of Polycystic Ovary Syndrome","volume":"39","author":"Jalil","year":"2024","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"111913","DOI":"10.1016\/j.mad.2024.111913","article-title":"The close relationship between oocyte aging and telomere shortening, and possible interventions for telomere protection","volume":"218","author":"Ozturk","year":"2024","journal-title":"Mech. Ageing Dev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1007\/s10815-024-03117-6","article-title":"Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes","volume":"41","author":"Fragkiadaki","year":"2024","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"430","DOI":"10.5468\/ogs.22170","article-title":"Can follicular fluid 8-oxo-2\u2032-deoxyguanosine predict the clinical outcomes in ICSI cycle among couples with normospermia male?","volume":"66","author":"Nori","year":"2023","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7265238","DOI":"10.1155\/2017\/7265238","article-title":"Oxidative Stress and Endometriosis: A Systematic Review of the Literature","volume":"2017","author":"Scutiero","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Xu, Y., Ning, L., Si, Y., Li, X., Wang, R., and Ren, Q. (2025). Metformin-mediated intestinal AMPK activation ameliorates PCOS through gut microbiota modulation and metabolic pathways. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1526109"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tang, H., Zhang, X., Hu, S., Song, Y., Jin, W., Zou, J., Zhang, Y., Guo, J., An, P., and Luo, J. (2025). Natural Products Acting as Senolytics and Senomorphics Alleviate Cardiovascular Diseases by Targeting Senescent Cells. Targets, 3.","DOI":"10.3390\/targets3030023"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Derevyanko, A., Skowronska, A., Skowronski, M.T., and Kordowitzki, P. (2022). The Interplay between Telomeres, Mitochondria, and Chronic Stress Exposure in the Aging Egg. Cells, 11.","DOI":"10.3390\/cells11162612"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s10815-022-02478-0","article-title":"On behalf of the Italian Society of Embryology, Reproduction and Research (SIERR). The process of ovarian aging: It is not just about oocytes and granulosa cells","volume":"39","author":"Camaioni","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/GME.0000000000000795","article-title":"Telomere length is longer in women with late maternal age","volume":"24","author":"Fagan","year":"2017","journal-title":"Menopause"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Herbert, M., Kalleas, D., Cooney, D., Lamb, M., and Lister, L. (2015). Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births. Cold Spring Harb. Perspect. Biol., 7.","DOI":"10.1101\/cshperspect.a017970"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1530\/REP-13-0223","article-title":"Telomerase activity is more significant for predicting the outcome of IVF treatment than telomere length in granulosa cells","volume":"147","author":"Wang","year":"2014","journal-title":"Reproduction"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1038\/s41467-025-57794-7","article-title":"Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization","volume":"16","author":"Winstanley","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1007\/s10815-023-02860-6","article-title":"Human granulosa cells of poor ovarian responder patients display telomeres shortening","volume":"40","author":"Yung","year":"2023","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4224417","DOI":"10.1155\/2022\/4224417","article-title":"The Predictive Levels of Serum Anti-M\u00fcllerian Hormone and the Combined Index of the Number of Retrieved Oocytes and Good-Quality Embryos in Advanced-Age Infertile Women","volume":"2022","author":"Sun","year":"2022","journal-title":"Int. J. Endocrinol."},{"key":"ref_111","first-page":"375","article-title":"The association of female and male infertility with telomere length (Review)","volume":"44","author":"Vasilopoulos","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_112","first-page":"305","article-title":"Telomere length: Lights and shadows on their role in human reproduction","volume":"100","author":"Rocca","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13048-025-01734-y","article-title":"Deciphering the interplay between oxidative stress and inflammation in polycystic ovary syndrome: Outcome of a case-control study","volume":"18","author":"Padder","year":"2025","journal-title":"J. Ovarian Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"F125","DOI":"10.1530\/REP-22-0189","article-title":"Oxidative stress and reproductive function: Sperm telomeres, oxidative stress, and infertility","volume":"164","author":"Moazamian","year":"2022","journal-title":"Reprod"},{"key":"ref_115","first-page":"419","article-title":"Impartial comparative analysis of measurement of leukocyte telomere length\/DNA content by Southern blots and qPCR","volume":"12","author":"Aviv","year":"2011","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11359\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:48:14Z","timestamp":1764067694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":115,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311359"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311359","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]}}}