Sexual dimorphism in lipidomic changes in maternal blood and placenta associated with obesity and gestational diabetes: A discovery study

Introduction: The placenta uses lipids and other nutrients to support its own metabolism hence impacting the type and amount of these substrates available to the growing fetus. Maternal obesity and gestational diabetes (GDM) can disrupt placental lipid metabolism and thus lead to altered fetal growth contributing to adverse pregnancy outcomes and developmentally programing the offspring for disease in later life. Understanding obesity and GDM driven changes in placental lipid metabolism is thus important.

Methods: We collected maternal plasma and placental villous tissue following elective cesarean section at term from women who were lean (pre-pregnancy BMI 18.5-24.9), obese (BMI>30) or obese with type A2 GDM n = 8 each group (4 male and 4 female placentas). Fatty acid composition of different lipid classes was analyzed by LC-MS/MS analysis. Significant changes in GDM vs obese, GDM vs lean, and obese vs lean were determined in both a fetal sex-dependent and independent manner.

Results: In placenta 436 lipids were identified, among which 85 showed significant changes. We report significant changes in placental triglyceride, phosphatidylcholine, and phosphatidylinositol lipids containing essential fatty acids- DHA and AA in GDM, with male placentas driving these changes. In maternal plasma, 284 lipids were identified with 14 showing significant changes, but we observed no changes based on fetal sex.

Discussion: Maternal obesity and GDM impact placental lipid composition in a sexually dimorphic manner. The alteration in specific lipid classes can impact cellular energetics and placental function.