Exploring the Placental Lipidome in Physically Active vs. Inactive Pregnancies

Physical activity during pregnancy is highly beneficial, but the mechanisms underlying these benefits have not been elucidated. Given its central role in supporting pregnancy, the placenta is a primary target for investigation. We implemented untargeted lipidomic analysis on 36 human placenta samples collected at term from uncomplicated pregnancies. Participant activity levels were objectively measured using accelerometry and participants were categorized as active or inactive. Samples were assessed by LC-MS/MS. The docosahexaenoic acid (DHA) transporter major facilitator superfamily domain-containing 2a (MFSD2a) was analyzed with western blot. A total of 192 lipids were annotated. Among these, 34 lipid species differed significantly between groups (|log2FC|  0.58; FDR-adjusted p value < 0.05). Multivariate analyses demonstrated modest separation between groups. DHA was identified in 17 lipid species, and seven were higher in the active group. Area under the receiver operating characteristic curve (AUROC) revealed five lipids with perfect group separation. Pathway analysis showed enrichment of the phosphatidylserine decarboxylase (PISD) pathway in the active group. No differences in MFSD2a expression were identified. The results demonstrate a relationship between physical activity and the placental lipidome. Several DHA species are higher in the active group, suggesting improved fetal availability for brain and retinal development. Lipids with perfect group separation may represent biomarkers of physical activity. Multiple lipid species and pathways warranting future targeted investigation are highlighted.