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Nutrigenomics and molecular nutrition

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

European Journal of Clinical Nutrition volume 74, pages 176–182 (2020)Cite this article

Subjects

Abstract

Objectives

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.

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 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.

Results

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.

Conclusion

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.

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Acknowledgements

We thank the pregnant women who participated in the study and doctors and nurses who made this study possible. The contribution of the research assistants Ms. Nancy, Ms. Roopa, Ms. Aruna, and Ms. Mary who collected the samples and data is acknowledged. Histopath technician Ms. Mahalakshmi assisted the pathologists in placental grossing experiments. We gratefully acknowledge the guiding role of Prof. T.S. Sridhar in initial establishment of human placental tissue-related protocols.

Funding

This work was supported by the Department of Biotechnology, Government of India (Grant Sanction order BT/PR10632/PFN/20/838/2013 to AM, AVK, JC, and PD and grant sanction order 102/IFD/SAN/749/2014-2015 AM, AVK, and PD).

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Author notes

  1. These authors contributed equally: C. Mani, P. Kochhar

Authors and Affiliations

  1. Division of Nutrition, St. John’s Research Institute, St. John’s Academy of Health Sciences, Bangalore, India

    C. Mani, P. Kochhar, P. Dwarkanath, A. V. Kurpad & A. Mukhopadhyay

  2. Department of Pathology, St John’s Medical College Hospital, Bangalore, India

    G. Ravikumar & J. Crasta

  3. Department of Obstetrics and Gynaecology, St John’s Medical College Hospital, Bangalore, India

    C. N. Sheela, S. George & A. Thomas

  4. Department of Biostatistics, St. John’s Medical College, St. John’s Academy of Health Sciences, Bangalore, India

    T. Thomas

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Mani, C., Kochhar, P., Ravikumar, G. et al. Placental expression of ENG, VEGF, and FLT: Gender-specific associations with maternal vitamin B12 status. Eur J Clin Nutr 74, 176–182 (2020). https://doi.org/10.1038/s41430-019-0449-2

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