Placental One-Carbon Metabolism Is Disrupted in Gestational Diabetes Mellitus Pregnancies

Background: The placenta plays a central role in the metabolic adaptations required for a healthy pregnancy and its dysfunction contributes to Gestational Diabetes Mellitus (GDM) development. We explored the placental metabolic profile, particularly metabolites of one-carbon metabolism, in GDM pregnancies and its association with maternal dietary methyl donor intake and neonatal outcomes. Methods: Dietary records were obtained from a prospective cohort with pregnant women. Groups were divided into control (n=13) and GDM (n=11). A subset of placental samples collected at delivery (control n=6; GDM n=5) was used for MS and NMR-based metabolomics. Results: Dietary intake was similar between the groups as well as the sum of dietary methyl donors (choline, betaine and methionine). Importantly, 100% of women presented with inadequate dietary choline. Placentas from pregnancies affected by GDM presented lower levels of choline, serine, glycine and SAM, despite good glycemic control and the absence of adverse neonatal outcomes. Conclusion: While the placenta demonstrated adaptive mechanisms that possibly mitigated placental stress, the long-term implications of these adaptations on offspring health remain uncertain. Given the critical role of methyl donors in epigenetic regulation and fetal programming, further research is needed to refine dietary guidelines, potentially guiding more tailored nutritional interventions focusing on choline supplementation during pregnancy.