Maternal stress in relation to sex-specific expression of placental genes involved in nutrient transport, oxygen tension, immune response, and the glucocorticoid barrier.

Introduction: Murine models provide evidence that maternal stress during pregnancy can influence placenta morphology and function, including altered expression of genes involved in the maintenance and progression of pregnancy and fetal development. Corresponding research evaluating the impact of maternal stress on placental gene expression in humans is limited. We examined maternal stress in relation to placental expression of 17 candidate genes in a community-based sample.

Methods: Participants included 60 mother-newborn pairs enrolled in the PRogramming of Intergenerational Stress Mechanisms pregnancy cohort based at the Mount Sinai Hospital in New York City. Placentas were collected immediately following delivery and gene expression was measured using a qPCR-based platform. Maternal experiences of traumatic and non-traumatic stress were measured using the Life Stressor Checklist-Revised (LSC-R) administered during a mid-pregnancy interview. We used multivariable linear regression to examine associations between LSC-R scores and expression of each gene in separate models in the sample overall and stratified by fetal sex.

Results: Higher maternal stress was associated with significantly increased placental expression of the nutrient sensor gene OGT, the glucose transporter gene GLUT1, and the hypoxia sensor gene HIF3A. In models stratified by fetal sex, significant associations remained only among males.

Discussion: This study represents one of the most comprehensive examinations of maternal lifetime traumatic and non-traumatic stress in relation to placental gene expression in human tissue. Our findings support that maternal stress may alter sex-specific placental expression of genes involved in critical developmental processes.