Maternal immunometabolism adaptation in pregnancy

Abstract

Pregnant women undergo a series of metabolic and immunologic changes to ensure provision of nutrients to, and prevent rejection of, the fetus. To ensure continuous supply of glucose to the fetus, the mother increases glucose production, glucose intolerance and insulin resistance. To meet her own energy demands, the mother transitions from lipid storage to lipolysis. To prevent rejection of the fetal semi-allograft, the mother’s immune system must be regulated, whilst maintaining protection against pathogens. Hypothesis: Well-recognised metabolic changes in pregnancy could impact maternal immune function. The aims of this project are to landscape the lipidomic profile using novel mass spectrometry techniques, and to determine whether monocytes undergo metabolic adaptation, if this occurs at 28 weeks of gestation, and if maternal obesity sabotages immunological adaptations. In addition, aims included investigation into the mechanisms which may protect the mother and fetus against SARS-CoV-2. Key findings unveiled significant phenotypic adaptations in the monocyte subsets during pregnancy, which are sabotaged by obesity. As the effect of maternal obesity is poorly understood, other immunological adaptations were investigated which revealed a shift to a Th1 and Th17 response which might contribute to the detrimental effects of obesity on pregnancy. At term, the monocytes illustrate a strong metabolic adaptation where their oxidative phosphorylation capabilities are reduced, confirmed by alterations in their mitochondria, with a downstream effect on their functionality with reduced production of lipid mediators and cytokines. While risk of infection with SARS-CoV-2 is low to pregnant women and the fetus, there is increased risk of preterm birth and admission into ICU. The fetus is relatively protected against infection, with cases of vertical transmission being rare. This thesis illustrates an elevated presence of soluble SARS-CoV-2 related molecules in breast milk and amniotic fluid which are postulated to act as decoy traps for the virus, which protects the neonate. In conclusion, this thesis has revealed novel findings into the immunometabolism adaptation to pregnancy.