{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:24Z","timestamp":1790834484582,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study characterized metabolomic profiles of maternal adipose tissue, placenta, and cord blood in pre-pregnancy obesity and explored links to adverse pregnancy outcomes (APOs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      From a prospective cohort (Oct 2024\u2013Oct 2025,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091,335), 25 obese (pre-pregnancy BMI\u2009\u2265\u200928\u2005kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) and 25 control women undergoing cesarean section were included. Visceral adipose, placenta, and umbilical vein plasma were analyzed using UHPLC-MS\/MS. Metabolite differences were analyzed using Random Forest modeling, OPLS-DA, KEGG pathway enrichment analysis, and correlation analysis with clinical indicators, including gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, macrosomia, postpartum hemorrhage (PPH), and various laboratory parameters. In an independent external cohort, mRNA expression levels of key steroidogenic enzymes in placental tissues were verified by qRT-PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The obesity group showed significantly higher incidences of GDM, HDP, PPH and higher neonatal weight. Vitamin B12 and folic acid were key discriminators across all compartments. Adipose tissue metabolites were enriched in arginine\/proline, pentose phosphate, and cysteine\/methionine metabolism. Placenta was enriched in steroid hormone biosynthesis pathways. Cord blood additionally showed enrichment in TCA cycle, glutamatergic and serotonergic synapses. Key compartment-specific metabolites included etiocholanolone (adipose), 16-glucuronide-estriol (placenta), and 5\n                      <jats:italic>\u03b1<\/jats:italic>\n                      -androstan-3-one (cord blood), all of which correlated with clinical indicators. The mRNA expression changes of key steroidogenic enzymes in placental tissues paralleled the alterations in their corresponding metabolite abundances.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pre-pregnancy obesity-related adverse pregnancy outcomes are driven by a disrupted maternal-fetal metabolic axis characterized by three core features: global dysfunction of one-carbon metabolism exemplified by vitamin B12 and folic acid abnormalities, placental steroid hormone biosynthesis abnormalities as the central hub, and disturbances in fetal energy and neurotransmitter metabolism as the downstream consequence. Monitoring these metabolites may enable early risk identification and guide targeted interventions for placental steroid metabolism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1904730","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:42:28Z","timestamp":1790833348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-site metabolomics reveals one-carbon and placental steroid disruption in maternal pre-pregnancy obesity linked to adverse pregnancy outcomes"],"prefix":"10.3389","volume":"13","author":[{"given":"Ke","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Obstetric, The Affiliated Lihuili Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetric, The Affiliated 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