Advanced Maternal Age and Fetal Sex Modulate Placentokines and Metabolic Glucose Biomarkers

Advanced Maternal Age and Fetal Sex Modulate Placentokines and Metabolic Glucose Biomarkers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Advanced Maternal Age and Fetal Sex Modulate Placentokines and Metabolic Glucose Biomarkers Maria Puche-Juarez, Juan M. Toledano, Catalina Paco Matallana, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8145672/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Advanced maternal age (AMA) is linked to an increased risk of obstetrical issues. Research to date has investigated the role of several placentokines related to adipose signalling and glucose metabolism biomarkers in pregnancy outcomes; however, AMA and neonatal sex are crucial factors that have not been considered in the study of metabolic function during pregnancy. The objective of this research was to elucidate the influence of AMA and neonatal sexual dimorphism on these placentokines and glucose homeostasis together with their possible relationships with the anthropometric characteristics of newborns. Methods A cohort of 184 nulliparous pregnant women were divided by age (≥ 35 years) and control (< 35 years). The expression of all biomarkers included in the analysis was measured in placental tissue. Results Insulin and visfatin levels were greater in the AMA group, whereas glucagon, PAI-1, resistin, and leptin levels were lower. In placentas from male AMA, insulin levels were higher and glucagon, leptin and resistin levels were lower than those in placentas from male control fetuses. Leptin levels were also lower in placentas from AMA male fetuses than in those from AMA female fetuses in both groups. Moreover, placental alterations associated with maternal age and fetal sex are correlated with distinct neonatal anthropometric parameters. Conclusions Nulliparous AMA mothers exhibit changes in placental metabolic signalling influenced by neonatal sexual dimorphism, with more pronounced effects in male neonates. These effects could influence fetal development and postnatal life. Pregnancy Advanced maternal age Adipokines Sexual dimorphism Placenta Anthropometry Neonatal outcomes Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 19 Dec, 2025 Editor invited by journal 24 Nov, 2025 Editor assigned by journal 19 Nov, 2025 Submission checks completed at journal 19 Nov, 2025 First submitted to journal 18 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8145672","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":563735219,"identity":"c2a431a0-9909-46a2-bf79-e2a06532f52d","order_by":0,"name":"Maria Puche-Juarez","email":"","orcid":"","institution":"University of Granada","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Puche-Juarez","suffix":""},{"id":563735220,"identity":"aae4fa07-0444-4314-888b-a2b8340ece94","order_by":1,"name":"Juan M. 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Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pregnancy, Advanced maternal age, Adipokines, Sexual dimorphism, Placenta, Anthropometry, Neonatal outcomes","lastPublishedDoi":"10.21203/rs.3.rs-8145672/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8145672/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAdvanced maternal age (AMA) is linked to an increased risk of obstetrical issues. Research to date has investigated the role of several placentokines related to adipose signalling and glucose metabolism biomarkers in pregnancy outcomes; however, AMA and neonatal sex are crucial factors that have not been considered in the study of metabolic function during pregnancy. The objective of this research was to elucidate the influence of AMA and neonatal sexual dimorphism on these placentokines and glucose homeostasis together with their possible relationships with the anthropometric characteristics of newborns.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA cohort of 184 nulliparous pregnant women were divided by age (\u0026ge;\u0026thinsp;35 years) and control (\u0026lt;\u0026thinsp;35 years). The expression of all biomarkers included in the analysis was measured in placental tissue.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eInsulin and visfatin levels were greater in the AMA group, whereas glucagon, PAI-1, resistin, and leptin levels were lower. In placentas from male AMA, insulin levels were higher and glucagon, leptin and resistin levels were lower than those in placentas from male control fetuses. Leptin levels were also lower in placentas from AMA male fetuses than in those from AMA female fetuses in both groups. Moreover, placental alterations associated with maternal age and fetal sex are correlated with distinct neonatal anthropometric parameters.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eNulliparous AMA mothers exhibit changes in placental metabolic signalling influenced by neonatal sexual dimorphism, with more pronounced effects in male neonates. These effects could influence fetal development and postnatal life.\u003c/p\u003e","manuscriptTitle":"Advanced Maternal Age and Fetal Sex Modulate Placentokines and Metabolic Glucose Biomarkers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-22 14:06:33","doi":"10.21203/rs.3.rs-8145672/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-12-19T10:19:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-24T20:31:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-19T08:04:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-19T08:04:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-11-18T12:50:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3eff0fd0-808b-4163-9a76-636d37d742ad","owner":[],"postedDate":"December 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T14:06:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-22 14:06:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8145672","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8145672","identity":"rs-8145672","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}