Maternal Diet Quality Is Associated with Placental Proteins in the Placental Insulin/Growth Factor, Environmental Stress, Inflammation, and mTOR Signaling Pathways: The Healthy Start ECHO Cohort

Abstract

Background: Maternal nutritional status affects placental function, which may underlie the intrauterine origins of obesity and diabetes. The extent to which diet quality is associated with placental signaling and which specific pathways are impacted is unknown.

Objectives: To examine sex-specific associations of maternal diet quality according to the Healthy Eating Index (HEI)-developed to align with recommendations from the Dietary Guidelines for Americans-with placental proteins involved in metabolism and mediators of environmental stress, inflammation, and growth factors.

Methods: Among 108 women from the Healthy Start cohort with a mean ± SD age of 29.0 ± 6.1 y and a prepregnancy BMI (in kg/m2) of 24.8 ± 5.3, we conducted multivariable linear regression analysis stratified by offspring sex. We adjusted for maternal race or ethnicity, age, education, prenatal smoking habits, and physical activity and tested for an association of maternal HEI >57 compared with ≤57 and the abundance and phosphorylation of key proteins involved in insulin/growth factor signaling; mediators of environmental stress, inflammation, and growth factors; mechanistic target of rapamycin signaling proteins; and energy sensing in placental villus samples. HEI >57 was chosen given its prior relevance among Healthy Start mother-child dyads.

Results: In adjusted models, HEI >57 was associated with greater abundance of insulin receptor β (0.80; 95% CI: 0.11, 1.49) in placentas of females. In males, maternal HEI >57 was associated with greater activation and abundance of select placental nutrient-sensing proteins and environmental stress, inflammation, and growth factor proteins (S6K1Thr389/S6K1: 0.81; 95% CI: 0.21, 1.41; JNK1Thr183/Tyr185/JNK1: 0.82; 95% CI: 0.27, 1.37; JNK2Thr183/Tyr185/JNK2: 0.57; 95% CI: 0.02, 1.11).

Conclusions: Higher-quality diet had sex-specific associations with placental protein abundance/phosphorylation. Given that these proteins have been correlated with neonatal anthropometry, our findings provide insight into modifiable factors and placental pathways that should be examined in future studies as potential links between maternal diet and offspring metabolic health. This trial was registered at clinicaltrials.gov as NCT02273297.

Keywords: fetal programming; human; maternal diet; placenta; pregnancy.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

Participant flowchart.

FIGURE 2

Unadjusted association of maternal Healthy Eating Index (HEI) score >57 compared with ≤57 during pregnancy and placental protein abundance by placental sex. The 95% CI and β of HEI >57 compared with HEI ≤57 for (A) proteins in insulin/growth factor signaling pathways; (B) proteins in environmental stress, inflammation, and growth factor signaling pathways; (C) proteins in mechanistic target of rapamycin complex (mTORC1) signaling pathways; (D) proteins in mTORC2 signaling pathways, and (E) proteins in energy-sensing pathways. Males, n = 57; females, n = 51. Estimates represent the log-transformed z-scored protein difference among women who reported an HEI score >57, such that a positive value indicates greater protein abundance, and a negative value indicates lower protein abundance. Akt, protein kinase B; AMPK, AMP-activated protein kinase; ERK(1/2), extracellular signal-regulated kinase 1/2; GSK3β, glycogen synthase kinase 3β; IGF-1r, insulin-like growth factor 1 receptor; IRβ, insulin receptor β; JNK1 and 2, c-Jun N-terminal kinase 1 and 2; p38MAPK, p38 mitogen-activated protein kinase; PKCα, protein kinase C α; RPS6, ribosomal protein S6; S6K1, p70 ribosomal protein S6 kinase 1; STAT3, signal transducer and activator of transcription 3; 4E-BP1, eukaryotic translation initiation factor 4E–binding protein 1.