Placental expression of ENG, VEGF, and FLT: Gender-specific associations with maternal vitamin B12 status.

Abstract

Adequate vitamin B12 is a requisite during pregnancy and its deficiency is linked with increased risk for adverse outcomes, likely mediated by impaired placental angiogenesis. Thus, we aimed to test associations of maternal vitamin B12 status with the placental expression of angiogenesis-associated genes ENG, VEGF, and FLT. In this retrospective case-control study, placental and maternal trimester 1 blood samples (n = 104) were collected from small for gestational age (SGA) and appropriate for gestational age (AGA) full-term singleton pregnancies. Maternal trimester 1 vitamin B12 status was measured. Placentae and neonates were weighed at birth. Realtime quantitative PCR was performed to assess placental transcript abundance of ENG, VEGF, and FLT normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal trimester 1 vitamin B12 status were evaluated. Placental ENG transcript abundance associated negatively with maternal trimester 1 vitamin B12 status (β = -0.461, P = 0.017, n = 104). This association was specific to the female births (β = -0.590, P = 0.014, n = 60). Placental VEGF transcript levels were negatively associated with maternal trimester 1 vitamin B12 status only in the female births (β = -1.995, P = 0.029). Placental FLT transcript levels were not associated with maternal trimester 1 vitamin B12 status. Maternal trimester 1 vitamin B12 status was associated negatively with placental ENG and VEGF expression predominantly in the female births. Therefore, we hypothesize that the placenta adapts to low maternal vitamin B12 status by up-regulating angiogenic pathways in a gender-specific manner.