The roles of maternal one-carbon metabolism and placental imprinted gene expression in placental development and somatic growth in a longitudinal birth cohort

Objectives: One-carbon nutrients and imprinted genes both play critical roles in placental development and somatic growth. We aimed to examine (1) the impact of maternal one-carbon nutrition on placental imprinted gene expression, placental development, and infant growth and (2) interactions between one-carbon nutrients and imprinted genes in placental development and infant growth. Methods: Women were interviewed prenatally about demographics and their alcohol, smoking, and drug use during pregnancy in a prospective longitudinal cohort study examining developmental effects of prenatal alcohol exposure in Cape Town, South Africa (N = 158). Erythrocyte folate, serum vitamin B12, and plasma choline concentrations were assayed at recruitment. Infant weight and height were assessed at age 2 weeks. Placental histopathology exams and placental expression of 109 imprinted genes (Nanostring) were assessed (n = 65). Results: In limma tests, women with plasma choline concentrations below the median had lower placental expression of EPS15, IGF2R, LINC00657, SGCE, ZC3H12C, and ZNF264 than women above the median (p < 0.05, FDR<0.10). In regression models adjusted for potential confounders, plasma choline (μM) was associated with larger placental weight (g) (B = 14.0(1.9, 26.2)) and reduced maternal vascular underperfusion (MVU) prevalence (B = −0.07(-0.12, −0.02). Trends were seen for mediation of the relation between choline and MVU by decreased LINC00657, ZC3H12C, and ZNF264 expression. In regression models examining plasma cholineXimprinted gene expression interaction effects, plasma choline modified relations of EPS15, ZC3H12C, and ZNF264 to placental weight and fetal growth. Conclusions: These findings suggest maternal choline status may impact placental and fetal development, with imprinted genes playing potential mechanistic roles.