{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:06:46Z","timestamp":1779451606532,"version":"3.53.1"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":111,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sichuan Science and Technology Program","award":["2026NSFSC1657"],"award-info":[{"award-number":["2026NSFSC1657"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"Abstract<\/jats:title>\n \n STUDY QUESTION<\/jats:title>\n What are the specific metabolic and lipidomic alterations in placental tissue and umbilical cord serum of pregnancies complicated by PCOS, and how do maternal testosterone levels and obesity status interplay with these changes at the maternal\u2013fetal interface?<\/jats:p>\n <\/jats:sec>\n \n SUMMARY ANSWER<\/jats:title>\n Pregnancies affected by PCOS exhibit distinct metabolomic and lipidomic reprogramming in both placental tissue and umbilical cord serum, characterized by alterations in key pathways such as tryptophan metabolism and fatty acid metabolism, with propionic and gluconic acids identified as central metabolic nodes; these changes are significantly associated with maternal testosterone levels and are differentially modulated by maternal obesity.<\/jats:p>\n <\/jats:sec>\n \n WHAT IS KNOWN ALREADY<\/jats:title>\n PCOS is known to adversely affect maternal and fetal metabolic health, carrying risks for intergenerational metabolic programming. However, the precise molecular nature of metabolic and lipidomic dysregulation at the maternal\u2013fetal interface, particularly the specific drivers of hyperandrogenism and its complex interplay with maternal obesity, remains poorly characterized.<\/jats:p>\n <\/jats:sec>\n \n STUDY DESIGN, SIZE, DURATION<\/jats:title>\n This prospective comparative study evaluated 48 pregnant women with PCOS and 50 healthy pregnant controls. All biological samples were collected at the time of term delivery.<\/jats:p>\n <\/jats:sec>\n \n PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n Participants were recruited from a tertiary care center. To minimize labor-induced metabolic confounding, all subjects underwent elective term cesarean sections. Untargeted metabolomics and lipidomics analyses were performed on strictly standardized maternal-side placental tissue and umbilical cord serum using liquid chromatography\u2013mass spectrometry. Statistical analyses included multivariable linear regression to adjust for confounders and LASSO regression for key feature selection. Participants were further stratified by pre-pregnancy BMI (obese: BMI \u226528\u2009kg\/m2 vs non-obese: BMI &lt;28\u2009kg\/m2) to assess the impact of maternal adiposity.<\/jats:p>\n <\/jats:sec>\n \n MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n PCOS pregnancies showed significantly distinct metabolomic and lipidomic profiles compared to controls in both placental tissue (407 differential metabolites, 186 differential lipids; FDR &lt; 0.05) and umbilical cord serum (330 differential metabolites, 314 differential lipids; FDR &lt; 0.05). Key enriched KEGG pathways included tryptophan metabolism, sphingolipid metabolism, and biosynthesis of unsaturated fatty acids. Maternal testosterone levels demonstrated strong and independent correlations with several key differential metabolites and lipids. Propionic acid and gluconic acid were identified as central metabolic nodes. Subgroup analysis revealed that maternal obesity exerts an additive metabolic burden that partially masks the intrinsic PCOS molecular phenotype. The role of chance was minimized by appropriate sample size, statistical adjustment for confounders, and the use of FDR correction for multiple comparisons where applicable.<\/jats:p>\n <\/jats:sec>\n \n LARGE SCALE DATA<\/jats:title>\n N\/A.<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n The cross-sectional design and single-center setting limit causal and longitudinal inferences. Methodological constraints, including the absence of pre-pregnancy hormonal profiles, the lack of concurrent maternal peripheral blood sampling, and the restriction to maternal-side placental tissue and elective cesarean deliveries, necessitate caution when extending these findings to systemic maternal metabolism or vaginal births.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n These findings significantly advance our understanding of the metabolic pathophysiology of PCOS during pregnancy, highlighting specific pathways and molecules at the maternal\u2013fetal interface. This knowledge could pave the way for identifying novel biomarkers for early risk stratification and developing targeted interventions to mitigate adverse metabolic programming in offspring of mothers with PCOS, potentially tailored by maternal obesity status.<\/jats:p>\n <\/jats:sec>\n \n STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n This study was supported by the Sichuan Science and Technology Program (2026NSFSC1657), the \u2018Talent Program\u2019 Cultivation Project of Chengdu Women\u2019s and Children\u2019s Central Hospital (No. YC2023002), the Health Commission of Sichuan Province (No. 20PJ184), and the Medical Scientific Research Project Funded by the Chengdu Municipal Health Commission (No. 2024247). The authors declare no competing interests.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/hropen\/hoag036","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T11:12:27Z","timestamp":1776510747000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic reprogramming in placenta and umbilical cord serum of polycystic ovary syndrome pregnancies: testosterone-associated alterations and interaction with obesity"],"prefix":"10.1093","volume":"2026","author":[{"given":"Huisheng","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Chengdu Women\u2019s and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiafei","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal-Fetal Medicine, Department of Biobank, 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