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

• Published in: European journal of clinical nutrition Vol. 74; no. 1; pp. 176 - 182
• Main Authors: Mani, C., Kochhar, P., Ravikumar, G., Dwarkanath, P., Sheela, C. N., George, S., Thomas, A., Crasta, J., Thomas, T., Kurpad, A. V., Mukhopadhyay, A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2020; Nature Publishing Group
• Subjects: 38; 38/39; 38/77; 631/337/2019; 692/308/2056; Abundance; Angiogenesis; Births; Clinical Nutrition; Cyanocobalamin; Epidemiology; Females; Gender; Gene expression; Genes; Gestational age; Health risk assessment; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Neonates; Placenta; Pregnancy; Public Health; Small for gestational age; Transcription; Vascular endothelial growth factor; Vitamin B12
• ISSN: 0954-3007; 1476-5640
• DOI: 10.1038/s41430-019-0449-2

Objectives Adequate vitamin B 12 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 B 12 status with the placental expression of angiogenesis-associated genes ENG , VEGF , and FLT . Subjects/Methods 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 B 12 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 B 12 status were evaluated. Results Placental ENG transcript abundance associated negatively with maternal trimester 1 vitamin B 12 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 B 12 status only in the female births ( β  = −1.995, P  = 0.029). Placental FLT transcript levels were not associated with maternal trimester 1 vitamin B 12 status. Conclusion Maternal trimester 1 vitamin B 12 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 B 12 status by up-regulating angiogenic pathways in a gender-specific manner.