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The placenta serves as a center for lipid synthesis and transport and plays a critical role in establishing GDM. Thus, the changes in the type and content of lipids in the placenta may contribute to the development of GDM. Here, we performed an untargeted lipidomic analysis to profile the alterations of lipids in the placenta induced by GDM. Principal component analysis (PCA) was used to reduce the dimensionality of lipid data, and orthogonal projections to latent structures-discriminate analysis (OPLS-DA) was launched to show the differences in the lipid profile between the GDM group and normal controls. Additional multivariate data processing was carried out, including classification, pathway analysis and correlation analysis between dysregulated lipids and maternal blood glucose levels. We finally identified 1202 lipids in positive mode and 924 lipids in negative mode, of which 63 lipids were strongly associated with GDM. Notably, most dysregulated lipids were clustered in two major subtypes: glycerophospholipids and glycerolipids. Consistently, a significant down-regulation of glycerophospholipid metabolism was observed from pathway analysis. In addition, we found that SHexCer(d50:1), TAG(15:0\/20:6\/20:6) and PE(18:1e\/21:2) were positively correlated with blood glucose levels, while PC(12:0\/22:3), PC(22:4e\/18:5) and PE(18:1e\/26:4) showed negative correlations. Combining these lipids with fasting blood glucose showed high accuracy in the discrimination of women with GDM. In general, we explored the placental lipidomic abnormalities induced by GDM, and these findings may help us understand the pathological mechanisms of GDM.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/d2mo00083k","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T07:22:01Z","timestamp":1650698521000},"page":"545-554","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A comparative lipidomic study of the human placenta from women with or without gestational diabetes mellitus"],"prefix":"10.1093","volume":"18","author":[{"given":"Dongmei","family":"Jiang","sequence":"first","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"},{"name":"School of Nursing, Nanjing Medical University a , Nanjing, Jiangsu, China \u00a0 chenboji@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"He","sequence":"additional","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"},{"name":"School of Nursing, Nanjing Medical University a , Nanjing, Jiangsu, China \u00a0 chenboji@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Hua","sequence":"additional","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"},{"name":"School of Nursing, Nanjing Medical University a , Nanjing, Jiangsu, China \u00a0 chenboji@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjian","family":"Shan","sequence":"additional","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"},{"name":"School of Nursing, Nanjing Medical University a , Nanjing, Jiangsu, China \u00a0 chenboji@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-0827","authenticated-orcid":false,"given":"Xianwei","family":"Cui","sequence":"additional","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9869-4228","authenticated-orcid":false,"given":"Chenbo","family":"Ji","sequence":"additional","affiliation":[{"name":"Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital b , Nanjing, Jiangsu, China \u00a0 xwcui@njmu.edu.cn"},{"name":"School of Nursing, Nanjing Medical University a , Nanjing, Jiangsu, China \u00a0 chenboji@njmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,23]]},"reference":[{"key":"2026010813074200100_cit1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11892-015-0699-x","article-title":"Prevalence of gestational diabetes and risk of progression to type 2 diabetes: A global perspective","volume":"16","author":"Zhu","year":"2016","journal-title":"Curr. Diabetes Rep."},{"key":"2026010813074200100_cit2","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1056\/NEJMoa0707943","article-title":"Hyperglycemia and adverse pregnancy outcomes","volume":"358","author":"Metzger","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2026010813074200100_cit3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ajog.2019.01.206","article-title":"Evidence in support of the International Association of Diabetes in Pregnancy study groups\u2019 criteria for diagnosing gestational diabetes mellitus worldwide in 2019","volume":"221","author":"Hod","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2026010813074200100_cit4","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nrendo.2016.98","article-title":"Lipidomics for studying metabolism","volume":"12","author":"Han","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"2026010813074200100_cit5","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1007\/s11427-019-1563-3","article-title":"Regulation of glucose and lipid metabolism in health and disease","volume":"62","author":"Chen","year":"2019","journal-title":"Sci. China: Life Sci."},{"key":"2026010813074200100_cit6","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.freeradbiomed.2019.05.029","article-title":"Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease","volume":"144","author":"Svegliati-Baroni","year":"2019","journal-title":"Free Radical Biol. Med."},{"key":"2026010813074200100_cit7","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1038\/s41467-019-11954-8","article-title":"Genetic architecture of human plasma lipidome and its link to cardiovascular disease","volume":"10","author":"Tabassum","year":"2019","journal-title":"Nat. Commun."},{"key":"2026010813074200100_cit8","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1093\/ajcn\/nqab242","article-title":"Plasma lipidomics in early pregnancy and risk of gestational diabetes mellitus: A prospective nested case-control study in Chinese women","volume":"114","author":"Wang","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"2026010813074200100_cit9","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.3390\/ijms22147452","article-title":"Lipid metabolism is dysregulated before, during and after pregnancy in a mouse model of gestational diabetes","volume":"22","author":"Furse","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026010813074200100_cit10","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1126\/scitranslmed.aay4145","article-title":"PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans","volume":"12","author":"Rojas-Rodriguez","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"2026010813074200100_cit11","first-page":"165535","article-title":"Placental structure in gestational diabetes mellitus","volume":"2020","author":"Carrasco-Wong","year":"1866","journal-title":"Biochim. Biophys. Acta, Mol. Basis Dis."},{"key":"2026010813074200100_cit12","first-page":"109","article-title":"Maternal and fetal lipid metabolism under normal and gestational diabetic conditions","volume":"26","author":"Herrera","year":"2016","journal-title":"Horm. Mol. Biol. Clin. Invest."},{"key":"2026010813074200100_cit13","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000504404","article-title":"Increased alkaline phosphatase in cord blood of obese diabetic mothers is associated to polyunstaurated fatty acid levels","volume":"75","author":"Prieto-S\u00e1nchez","year":"2019","journal-title":"Ann. Nutr. Metab."},{"key":"2026010813074200100_cit14","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.2337\/db10-1434","article-title":"Dysregulation of placental endothelial lipase in obese women with gestational diabetes mellitus","volume":"60","author":"Gauster","year":"2011","journal-title":"Diabetes"},{"key":"2026010813074200100_cit15","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.placenta.2017.07.001","article-title":"Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition","volume":"57","author":"Segura","year":"2017","journal-title":"Placenta"},{"key":"2026010813074200100_cit16","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/nprot.2011.335","article-title":"Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry","volume":"6","author":"Dunn","year":"2011","journal-title":"Nat. Protoc."},{"key":"2026010813074200100_cit17","author":"Ying-chun"},{"key":"2026010813074200100_cit18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s11090-020-10147-2","article-title":"Metabolome analysis of selective inactivation of human melanoma and normal cells by cold atmospheric plasma","volume":"41","author":"Tian","year":"2021","journal-title":"Plasma Chem. Plasma Process."},{"key":"2026010813074200100_cit19","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1002\/mrm.27658","article-title":"Evaluation of principal component analysis image denoising on multi-exponential MRI relaxometry","volume":"81","author":"Does","year":"2019","journal-title":"Magn. Reson. Med."},{"key":"2026010813074200100_cit20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1021\/ac0713510","article-title":"Visualization of GC\/TOF-MS-based metabolomics data for identification of biochemically interesting compounds using OPLS class models","volume":"80","author":"Wiklund","year":"2008","journal-title":"Anal. Chem."},{"issue":"Suppl","key":"2026010813074200100_cit21","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1194\/jlr.R800095-JLR200","article-title":"Update of the LIPID MAPS comprehensive classification system for lipids","volume":"50","author":"Fahy","year":"2009","journal-title":"J. Lipid Res."},{"key":"2026010813074200100_cit22","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s40618-016-0607-5","article-title":"Gestational diabetes mellitus: An updated overview","volume":"40","author":"Chiefari","year":"2017","journal-title":"J. Endocrinol. Invest."},{"key":"2026010813074200100_cit23","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cca.2017.02.008","article-title":"The pathogenesis and pathophysiology of gestational diabetes mellitus: Deductions from a three-part longitudinal metabolomics study in China","volume":"468","author":"Law","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"2026010813074200100_cit24","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.12659\/MSM.903565","article-title":"Interleukin 6 (IL-6) and tumor necrosis factor \u03b1 (TNF-\u03b1) single nucleotide polymorphisms (SNPs), inflammation and metabolism in gestational diabetes mellitus in inner mongolia","volume":"23","author":"Zhang","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"2026010813074200100_cit25","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.3390\/ijms19113342","article-title":"The Pathophysiology of Gestational Diabetes Mellitus","volume":"19","author":"Plows","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2026010813074200100_cit26","doi-asserted-by":"crossref","first-page":"e24096","DOI":"10.1002\/jcla.24096","article-title":"Placental metabolic profiling in gestational diabetes mellitus: An important role of fatty acids","volume":"35","author":"Yang","year":"2021","journal-title":"J. Clin. Lab. Anal."},{"key":"2026010813074200100_cit27","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.diabres.2015.05.032","article-title":"Effects of obesity and gestational diabetes mellitus on placental phospholipids","volume":"109","author":"Uhl","year":"2015","journal-title":"Diabetes Res. Clin. Pract."},{"key":"2026010813074200100_cit28","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1093\/ajcn\/nqab242","article-title":"Plasma lipidomics in early pregnancy and risk of gestational diabetes mellitus: A prospective nested case-control study in Chinese women","volume":"114","author":"Wang","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"2026010813074200100_cit29","doi-asserted-by":"crossref","first-page":"e59153","DOI":"10.7554\/eLife.59153","article-title":"Underlying dyslipidemia postpartum in women with a recent GDM pregnancy who develop type 2 diabetes","volume":"9","author":"Lai","year":"2020","journal-title":"eLife"},{"key":"2026010813074200100_cit30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.placenta.2017.08.004","article-title":"Lipidomic analysis reveals the significant increase in diacylglycerophosphocholines in umbilical cord blood from pregnant women with gestational hypercholesterolemia","volume":"59","author":"Zhang","year":"2017","journal-title":"Placenta"},{"key":"2026010813074200100_cit31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jgg.2019.11.009","article-title":"Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression","volume":"47","author":"Wang","year":"2020","journal-title":"J. Genet. Genomics"},{"key":"2026010813074200100_cit32","doi-asserted-by":"crossref","first-page":"864","DOI":"10.12998\/wjcc.v8.i5.864","article-title":"Study on the correlation and predictive value of serum pregnancy-associated plasma protein A, triglyceride and serum 25-hydroxyvitamin D levels with gestational diabetes mellitus","volume":"8","author":"Ren","year":"2020","journal-title":"World J. Clin. Cases"},{"key":"2026010813074200100_cit33","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s12916-021-02095-1","article-title":"Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: The SWIFT study","volume":"19","author":"Zhang","year":"2021","journal-title":"BMC Med."},{"key":"2026010813074200100_cit34","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1194\/jlr.R046094","article-title":"Diversity and function of membrane glycerophospholipids generated by the remodeling pathway in mammalian cells","volume":"55","author":"Hishikawa","year":"2014","journal-title":"J. Lipid Res."},{"key":"2026010813074200100_cit35","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/MOL.0b013e328082e4d5","article-title":"Membrane lipids as signaling molecules","volume":"18","author":"Fernandis","year":"2007","journal-title":"Curr. Opin. Lipidol."},{"key":"2026010813074200100_cit36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cca.2021.02.023","article-title":"Plasma metabolites, especially lipid metabolites, are altered in pregnant women with gestational diabetes mellitus","volume":"517","author":"Zhan","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"2026010813074200100_cit37","first-page":"1558","article-title":"The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease","volume":"2017","author":"van der Veen","year":"1859","journal-title":"Biochim. Biophys. Acta, Biomembr."}],"container-title":["Molecular Omics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/molecular-omics\/article-pdf\/18\/6\/545\/65033131\/d2mo00083k.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molecular-omics\/article-pdf\/18\/6\/545\/65033131\/d2mo00083k.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:10:24Z","timestamp":1767895824000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/molecular-omics\/article\/18\/6\/545\/8286531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,23]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,4,23]]}},"URL":"https:\/\/doi.org\/10.1039\/d2mo00083k","relation":{},"ISSN":["2515-4184"],"issn-type":[{"value":"2515-4184","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,1]]},"published":{"date-parts":[[2022,4,23]]}}}