{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:54:56Z","timestamp":1781758496570,"version":"3.54.5"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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>Objective<\/jats:title>\n                    <jats:p>In recent years, advancements in metabolomics have highlighted that changes in metabolic states within the body might also be closely related to missed abortion. However, the specific impacts of metabolic abnormalities on missed abortion remain unclear. This study screened differential metabolites in serum and villous tissues from patients with missed abortion, analyzed possible mechanisms linking metabolic disturbances to disease occurrence, and explored their clinical research value in early pregnancy abnormality research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Focusing on the effect of abnormal levels of metabolites on missed abortion, a prospective case\u2013control study was conducted including 78 women with missed abortion and 75 women with normal early pregnancy undergoing elective termination. Targeted metabolomics profiling of serum and villous tissues was performed using mass spectrometry. Clinical characteristics and metabolite levels were compared between groups. Firth\u2019s logistic regression was applied to assess independent associations. ROC curve analysis was used to evaluate the discriminatory potential of key metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Results revealed metabolic differences in both serum and villous tissues between the missed abortion and control groups. Serum was characterized by upregulated amino acid metabolism, with elevated levels of multiple amino acids including ORN and TYR, which were associated with the risk of missed abortion. Villous tissues exhibited core disturbances in acylcarnitine metabolism, with C10:1 and C18 significantly upregulated in the missed abortion group. Notably, no highly consistent differential metabolites were identified between serum and villous tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates distinct metabolic signatures in missed abortion, with amino acid upregulation in serum and acylcarnitine disorder in villous tissues. Only CIT was consistently upregulated in both matrices, possibly due to limited assay coverage. Combined panels of the top eight FDR-ranked metabolites achieved high AUCs in serum and villous tissue, offering good auxiliary discrimination for missed abortion. These findings provide new insights into its metabolic pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1782638","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:37:10Z","timestamp":1781757430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of metabolites in serum and villous tissue of missed abortion patients based on targeted metabolomics"],"prefix":"10.3389","volume":"17","author":[{"given":"Huan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Gynecology, Northwest Women\u2019s and Children\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Northwest Women\u2019s and Children\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doudou","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Northwest Women\u2019s and Children\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Northwest Women\u2019s and Children\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muxi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Northwest Women\u2019s and Children\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Northwest Women\u2019s and Children\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2147\/IJWH.S507470","article-title":"Vitamin D, homocysteine, and thyroid dysfunction as risk factors for missed abortion: A retrospective risk factor analysis","volume":"17","author":"Fang","year":"2025","journal-title":"Ijwh"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.14849","article-title":"Traditional karyotyping vs copy number variation sequencing for detection of chromosomal abnormalities associated with spontaneous miscarriage","volume":"46","author":"Liu","year":"2015","journal-title":"Ultrasound Obstet Gynecol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2020.1821616","article-title":"A survey of influencing factors of missed abortion during the two-child peak period","volume":"41","author":"Gong","year":"2021","journal-title":"J Obstet Gynaecol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26175231","article-title":"Enantioselectivity effects in clinical metabolomics and lipidomics","volume":"26","author":"Oliveira","year":"2021","journal-title":"Molecules"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1021\/pr200352m","article-title":"Metabolic biomarkers of prenatal disorders: An exploratory NMR metabonomics study of second trimester maternal urine and blood plasma","volume":"10","author":"Diaz","year":"2011","journal-title":"J Proteome Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2012.680254","article-title":"Metabolomics and first-trimester prediction of early-onset preeclampsia","volume":"25","author":"Bahado-Singh","year":"2012","journal-title":"J Maternal-Fetal Neonatal Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.fertnstert.2012.01.122","article-title":"An investigation into the relationship between the metabolic profile of follicular fluid, oocyte developmental potential, and implantation outcome","volume":"97","author":"Wallace","year":"2012","journal-title":"Fertility Sterility"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1038\/s41598-019-39259-2","article-title":"Urinary metabolic variation analysis during pregnancy and application in gestational diabetes mellitus and spontaneous abortion biomarker discovery","volume":"9","author":"Liu","year":"2019","journal-title":"Sci Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/life12010086","article-title":"The interplay between pathophysiological pathways in early-onset severe preeclampsia unveiled by metabolomics","volume":"12","author":"Youssef","year":"2022","journal-title":"Life"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.818888","article-title":"Age-dependent metabolomic profile of the follicular fluids from women undergoing assisted reproductive technology treatment","volume":"13","author":"Huang","year":"2022","journal-title":"Front Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cca.2021.03.012","article-title":"Serum metabolite signatures of epithelial ovarian cancer based on targeted metabolomics","volume":"518","author":"Wang","year":"2021","journal-title":"Clin Chim Acta"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.3770","article-title":"Plasma metabolomic profile and potential biomarkers for missed abortion","volume":"30","author":"Fei","year":"2016","journal-title":"BioMed Chromatogr"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.01.096","article-title":"NMR-based serum metabolomics study reveals a innovative diagnostic model for missed abortion","volume":"496","author":"Wu","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.15417","article-title":"Using liquid chromatography and mass spectrometry to predict potential biomarkers for missed miscarriage and its metabolic pathways in a tertiary center: A cross\u2010sectional analytic study","volume":"166","author":"Xia","year":"2024","journal-title":"Intl J Gynecology Obste"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/nu13093080","article-title":"Longitudinal plasma metabolomics profile in pregnancy-a study in an ethnically diverse U.S. pregnancy cohort","volume":"13","author":"Mitro","year":"2021","journal-title":"Nutrients"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2016.13.236","article-title":"First-trimester maternal serum amino acids and acylcarnitines are significant predictors of gestational diabetes","volume":"13","author":"Nevalainen","year":"2016","journal-title":"Rev Diabetes Stud"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7499\/j.issn.1008-8830.2109149","article-title":"Characteristics of amino acid metabolism in preterm infants in Guangxi, China","volume":"24","author":"Lin","year":"2022","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"B18","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1186\/s12967-025-06341-5","article-title":"Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: Beyond fatty acid oxidation","volume":"23","author":"Xiang","year":"2025","journal-title":"J Transl Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/86.4.1024","article-title":"Arginine flux and intravascular nitric oxide synthesis in severe childhood undernutrition","volume":"86","author":"Jahoor","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s13023-023-02800-8","article-title":"Citrulline in the management of patients with urea cycle disorders","volume":"18","author":"Imbard","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s00726-005-0235-4","article-title":"Almost all about citrulline in mammals","volume":"29","author":"Curis","year":"2005","journal-title":"Amino Acids"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3360001","article-title":"Arginine metabolism: Nitric oxide and beyond","volume":"336","author":"Wu","year":"1998","journal-title":"Biochem J"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1782638\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:37:15Z","timestamp":1781757435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1782638\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":22,"alternative-id":["10.3389\/fendo.2026.1782638"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1782638","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]},"article-number":"1782638"}}