Placental miRNAs Targeting Cellular Stress Response Pathways Are Highly Expressed in Non-Hispanic Black People.

Non-Hispanic Black (NHB) people have a 2.5-fold higher risk of maternal mortality when compared to non-Hispanic White (NHW) people. Neonates of NHB people are more likely to be born preterm and small for gestational age, which may be driven by structural racism. The placenta is very sensitive to the maternal environment and may play a critical role in the translation of environmental stressors to pregnancy outcomes. Our aim was to assess the placental miRNA expression profile in both NHB and NHW people and the association between differentially expressed miRNAs and pregnancy outcomes. Placentas were collected from 50 NHB and 74 NHW people with a normal singleton pregnancy undergoing elective cesarean section at term prior to the onset of labor. Placental miRNA expression was measured via whole-genome small RNA-sequencing in a subset of 77 placentas. Fifteen miRNAs were more highly expressed in the placentas of NHB people. Several of these miRNAs were associated with cellular stress response pathways, suggesting that they may be responding to environmental stressors. Placental miR-192-5p expression was lower among NHB people and was positively associated with neonatal adiposity, suggesting it may be sensitive to structural racism with potential impacts on fetal growth.

Placental miR-3940-3p Is Associated With Maternal Insulin Resistance in Late Pregnancy.

CONTEXT: An increase in maternal insulin resistance (IR) during pregnancy is essential for normal fetal growth. The mechanisms underlying this adaptation are poorly understood. Placental factors are believed to instigate and maintain these changes, as IR decreases shortly after delivery. Methylation of placental gene loci that are common targets for miRNAs are associated with maternal IR. OBJECTIVE: We hypothesized that placental miRNAs targeting methylated loci are associated with maternal IR during late pregnancy. METHODS: We collected placentas from 132 elective cesarean sections and fasting blood samples at delivery to estimate maternal homeostasis model assessment of insulin resistance (HOMA-IR). Placental miRNA expression was measured via whole genome small-RNA sequencing in a subset of 40 placentas selected by maternal pre-gravid body mass index (BMI) and neonatal adiposity. Five miRNAs correlated with maternal HOMA-IR and previously identified as targeting methylated genes were selected for validation in all 132 placenta samples via RT-qPCR. Multiple regression adjusted for relevant clinical variables. RESULTS: Median maternal age was 27.5 years, with median pre-pregnancy BMI of 24.7 kg/m2, and median HOMA-IR of 2.9. Among the 5 selected miRNA, maternal HOMA-IR correlated with the placental expression of miRNA-371b-3p (r = 0.25; P = 0.008) and miRNA-3940-3p (r = 0.32; P = 0.0004) across the 132 individuals. After adjustment for confounding variables, placental miRNA-3940-3p expression remained significantly associated with HOMA-IR (ß = 0.16; P = 0.03). CONCLUSION: Placental miRNA-3940-3p was associated with maternal IR at delivery. This placental miRNA may have an autocrine or paracrine effect-regulating placental genes involved in modulating maternal IR.

Placental Impact of Dietary Supplements: More Than Micronutrients.

PURPOSE: Maternal nutrition is a key modifier of fetal growth and development. However, many maternal diets in the United States do not meet nutritional recommendations. Dietary supplementation is therefore necessary to meet nutritional goals. The effects of many supplements on placental development and function are poorly understood. In this review, we address the therapeutic potential of maternal dietary supplementation on placental development and function in both healthy and complicated pregnancies. METHODS: This is a narrative review of original research articles published between February 1970 and July 2020 on dietary supplements consumed during pregnancy and placental outcomes (including nutrient uptake, metabolism and delivery, as well as growth and efficiency). Impacts of placental changes on fetal outcomes were also reviewed. Both human and animal studies were included. FINDINGS: We found evidence of a potential therapeutic benefit of several supplements on maternal and fetal outcomes via their placental impacts. Our review supports a role for probiotics as a placental therapeutic, with effects that include improved inflammation and lipid metabolism, which may prevent preterm birth and poor placental efficiency. Supplementation with omega-3 fatty acids (as found in fish oil) during pregnancy tempers the negative effects of maternal obesity but may have little placental impact in healthy lean women. The beneficial effects of choline supplementation on maternal health and fetal growth are largely attributable to its placental impacts. l-arginine supplementation has a potent provascularization effect on the placenta, which may underlie its fetal growth-promoting properties. IMPLICATIONS: The placenta is exquisitely sensitive to dietary supplements. Pregnant women should consult their health care practitioner before continuing or initiating use of a dietary supplement. Because little is known about impacts of many supplements on placental and long-term offspring health, more research is required before robust clinical recommendations can be made.