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

J Nutr. 2022 Mar 3;152(3):816-825. doi: 10.1093/jn/nxab403.


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 as NCT02273297.

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

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Diet
  • Female
  • Humans
  • Infant, Newborn
  • Inflammation / metabolism
  • Insulin* / metabolism
  • Insulin, Regular, Human
  • Male
  • Placenta / metabolism
  • Pregnancy
  • Pregnancy Proteins* / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism


  • Insulin
  • Insulin, Regular, Human
  • Pregnancy Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases

Associated data