title: Lipidomic analysis of human placental syncytiotrophoblast microvesicles in adverse pregnancy outcomes.
abstract: OBJECTIVE
  Syncytiotrophoblast microvesicles (STBM) are shed from placenta into the maternal circulation. STBM circulate in increased amounts in adverse pregnancies, e.g., preeclampsia and recurrent miscarriages (RM). Recently dysregulation of lipid metabolites has been proposed to be associated with their pathogenesis. Lipid composition of STBM in healthy and adverse pregnancies remains unknown.
  
  
  OBJECTIVE
  To determine lipid composition of STBM and whether STBM lipid composition differs in pathologic and normal pregnancies.
  
  
  METHODS
  Patients with Preeclampsia (n = 6) or history of RM (n = 9) (>2 consecutive losses <20 weeks) and gestational age-matched normal pregnant controls (same number as cases) were recruited. STBM were prepared from placental explant culture supernatant. Lipid profiling of STBM was performed by mass spectrometry in combination with liquid chromatography. We quantified ∼200 lipids in STBM including (i) glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA); (ii) sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucosylceramide, GluCer; ganglioside mannoside 3, GM3); (iii) free cholesterol and cholesteryl esters, CE.
  
  
  RESULTS
  The major lipid classes in STBM were SM, Chol, PS, PC and PI, along with PA and GM3 enrichments. SM/PC ratio showed a unique reversal (3:1) compared to that normally found in human cells or plasma. Level of total PS was significantly upregulated (p < 0.005) in preeclampsia patients, while PI (p < 0.0005), PA (p < 0.005), and GM3 (p < 0.05) were significantly downregulated. Similar trends were obtained in RM.
  
  
  CONCLUSIONS
  Differential lipid expression of STBM in preeclampsia or RM includes those that are implicated in immune response, coagulation, oxidative stress, and apoptosis.
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore & National University Health System, 10 Medical Drive, Singapore 119260, Singapore. soniabaig@nus.edu.sg
authors: S
authors: S
authors: Baig
authors: J Y
authors: JY
authors: Lim
authors: A Z
authors: AZ
authors: Fernandis
authors: M R
authors: MR
authors: Wenk
authors: A
authors: A
authors: Kale
authors: L L
authors: LL
authors: Su
authors: A
authors: A
authors: Biswas
authors: S
authors: S
authors: Vasoo
authors: G
authors: G
authors: Shui
authors: M
authors: M
authors: Choolani
mesh_terms: D000026:Abortion, Habitual / Q000378:metabolism*; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001777:Blood Coagulation / Q000502:physiology; D002784:Cholesterol / Q000032:analysis; D002788:Cholesterol Esters / Q000032:analysis; D005260:Female; D020404:Glycerophospholipids / Q000032:analysis; D006801:Humans; D007109:Immunity / Q000502:physiology; D008055:Lipids / Q000032:analysis* / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D013107:Sphingolipids / Q000032:analysis; D014327:Trophoblasts / Q000737:chemistry*
chemical_list: D002788:Cholesterol Esters; D020404:Glycerophospholipids; D008055:Lipids; D013107:Sphingolipids; D002784:Cholesterol