Abstract
Objectives
Imprinted genes are epigenetically regulated and play critical roles in placental development and fetal growth. We aimed to examine (1) the impact of maternal one-carbon (methyl donor) nutrition on placental imprinted gene expression, placental development, and fetal growth; (2) whether imprinted gene expression alterations mediate effects of one-carbon nutrition on placental development and fetal growth; (3) interaction effects between one-carbon nutrients and imprinted genes in placental development and fetal growth.
Methods
Histopathology and expression of 109 imprinted genes (Nanostring) were assessed in placentas from 101 women recruited at initiation of antenatal care in a prospective cohort study examining developmental effects of prenatal alcohol exposure in South Africa. Women were interviewed prenatally about demographics, alcohol, smoking, and drug use, and erythrocyte folate, serum vitamin B12, and plasma choline concentrations were assayed at recruitment. Infant weight and height were assessed at age 2 wk.
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 < .05, FDR < .10). In regression models adjusted for potential confounders (maternal age, gravidity, education, alcohol and drug use), 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 = −.07(−.12, −.02). In causal inference analyses, there were trends for mediation of the relation between choline and MVU by decreased LINC00657, ZC3H12C, and ZNF264 expression. In regression models examining plasma choline X imprinted gene expression interaction effects, choline modified relations of EPS15, ZC3H12C, and ZNF264 to placental weight and fetal growth.
Conclusions
Maternal plasma choline was associated with decreased placental expression of 6 imprinted genes, 3 of which may mediate effects of choline on placental development. Choline modified effects of 3 genes on placental and fetal growth. These findings suggest maternal choline status may impact placental and fetal development, with imprinted genes playing mechanistic roles.
Funding Sources
NIH/NIAAA; Lycaki-Young Fund.
Effects of Assisted Reproduction Technology on Placental Imprinted Gene Expression