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Research Project: Impact of Maternal Influence and Early Dietary Factors on Child Growth, Development, and Metabolic Health

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Title: Associations between maternal body mass index and diet composition with placental DNA methylation at term

Author
item THAKALI, KESHARI - Arkansas Children'S Nutrition Research Center (ACNC)
item ZHONG, YING - Arkansas Children'S Nutrition Research Center (ACNC)
item CLEVES, MARIO - University Of South Florida
item ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - University Of Colorado

Submitted to: Placenta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2020
Publication Date: 2/26/2020
Citation: Thakali, K.M., Zhong, Y., Cleves, M., Andres, A., Shankar, K. 2020. Associations between maternal body mass index and diet composition with placental DNA methylation at term. Placenta. 93:74-82. https://doi.org/10.1016/j.placenta.2020.02.018.
DOI: https://doi.org/10.1016/j.placenta.2020.02.018

Interpretive Summary: The placenta is a vital organ in fetal growth and development and mediates nutrient transport to support fetal growth. While it is known that the placenta integrates information from both the mother and baby and responds by altering its structure and function to optimize mother and baby's health at birth, it is still unclear if the maternal environment during pregnancy affects placental DNA methylation. We collected placenta from normal weight and overweight/obese mothers to see if maternal BMI or diet composition altered placental DNA methylation. Our studies demonstrate that maternal obesity and maternal saturated fat intake are associated with altered placental DNA methylation patterns, and may be contribute to maternal obesity-associated changes in placental function.

Technical Abstract: Maternal obesity and poor quality diets are associated with greater risk of obesity in offspring. Maternal diet and obesity influence placental gene expression and nutrient transport, but the impact of diet and obesity on global epigenetic changes in the placenta are poorly understood. We hypothesized that placental DNA methylation patterns are associated with maternal body mass index (BMI) and/or maternal diet composition. Using reduced representation bisulfite sequencing (RRBS), we assessed genome scale DNA methylation of ~300,000 CpGs in 150 term placentas from normal weight mothers (n = 72) and overweight/obese mothers (n = 78). Maternal BMI was assessed before week 10 of gestation and maternal macronutrient diet composition was assessed using 3-day food records at each trimester. In multivariable linear regression models, maternal BMI category (normal weight or overweight/obese), BMI (kg/m2), and maternal saturated fat consumption (g/d) were associated (p < 0.0001) with methylation of 185, 103, and 302 CpGs, respectively. Of the 56 CpGs associated (p < 0.0001) with both maternal BMI category and maternal BMI, GO analysis showed biological processes related to SREBP signaling, phospholipid transport, granulocyte differentiation, and RNA pol II transcription to be affected. Maternal saturated fat intake was associated with methylation of 302 CpGs (p < 0.0001). These genes were related to chromatin remodeling, IGF receptor, PI3K, and nitric oxide synthase signaling. These data suggest that placental DNA methylation status is associated with both maternal obesity and maternal saturated fat intake, possibly contributing to maternal obesity-associated changes in placental function.