Maternal diet quality and circulating extracellular vesicle and particle miRNA during pregnancy

Abstract

Purpose: During pregnancy, extracellular vesicle and particle microRNAs (EVP miRNA) in maternal circulation have the capacity to cross the placenta and facilitate maternal-fetal communication. Both dysregulation of circulating EVP miRNA during pregnancy and maternal diet quality have been previously associated with pregnancy complications and adverse birth outcomes. However, little is known about how maternal diet influences circulating EVP miRNA during pregnancy. This study assesses associations between maternal diet quality, as measured by the Alternative Healthy Eating Index (2010; AHEI-2010), and EVP miRNA levels in maternal circulation during pregnancy.

Methods: In a pilot study of 53 pregnant participants in the New Hampshire Birth Cohort Study, maternal diet quality was assessed using AHEI-2010 and plasma (mean gestational age at blood collection: 28.8 weeks) EVP miRNA were profiled using the NanoString nCounter platform which interrogates 798 miRNA transcripts.

Results: In covariate-adjusted models, the AHEI-2010 adherence score was negatively associated (P < 0.05) with the number of unique miRNA transcripts detectable in each sample. In post hoc analyses, greater consumption of red and processed meats was positively associated with levels of 7 miRNA (Q < 0.05), including hsa-miR-512-5p (P_Bonf < 0.01), a member of the placenta-specific chromosome 19 miRNA cluster.

Conclusion: We identified associations between the consumption of red and processed meat and levels of circulating select EVP miRNA during pregnancy, including placenta-specific miRNA and miRNA with target genes overrepresented in pathways involved in placental development. Additional research is needed to assess whether alterations in maternal circulating EVP miRNA may mediate maternal diet quality's impacts on pregnancy and birth outcomes.

Keywords: Alternative Healthy Eating Index 2010; Diet; Extracellular vesicles; Plasma; Pregnancy; miRNA.

Fig. 1

Covariate-adjusted associations between the overall AHEI-2010 score and each of its component scores with sample richness. Sample richness reflects the number of unique miRNA transcripts detected in a sample. Each component score was modeled separately as the dependent variable using linear regression. All models were adjusted for educational attainment (binary), vigorous physical activity (hrs/week) and time of day at blood collection (binary). Additionally, models for component scores were adjusted for total caloric intake. Results in green reflect positively scored dietary components and results in magenta reflect negatively scored dietary components of AHEI-2010

Fig. 2

(A)Volcano plot of covariate-adjusted associations between the AHEI-2010 component score for red and processed meat consumption and richness-associated miRNA detectable in more than 60% of samples. MiRNA counts were log₂-transformed and modeled using robust linear regression adjusting for maternal educational attainment (binary), vigorous physical activity (hrs/wk), time of day at blood collection (binary), and total caloric intake (kcal/day). Statistically significant associations after FDR correction (Q < 0.05) are colored in red and labeled. The red dashed line reflects a Bonferroni-adjusted significance threshold of P_Bonf < 0.01. (B) Volcano plot of covariate-adjusted associations between the AHEI-2010 component score for red and processed meat consumption and richness-associated miRNAs detectable in 20–60% of samples. EVP miRNA treated as binary variables (detectable vs. not detectable) were modeled using robust logistic regression. Models were adjusted for maternal educational attainment (binary), vigorous physical activity (hrs/wk), time of day at blood collection (binary), and total caloric intake (kcal/day). (C) Results from enrichment analyses conducted using EnrichR for the 1,154 high confidence target genes (identified by mirDIP) for the 7 red and processed meat consumption-associated miRNA (Q < 0.05)