Circular RNAs mediate the regulation of maternal placental nutrient transport and fetal development by sugar-sweetened beverages

Abstract

Epidemiological and experimental studies have demonstrated a strong association between maternal diet and fetal birth weight, obesity, and metabolic syndrome. We investigated the pathways and modes of action of circular RNAs (circRNAs) that mediate the regulation of maternal reproductive performance and fetal development by sugar-sweetened beverages (20 % sucrose water, SSBs) using C57BL/6J mice as a model. Results showed that SSBs significantly increased the reproductive performance (P<0.05), body weight (P<0.01), fetal birth weight (P<0.05), placental weight (P<0.01), and the expression of nutrient transporter genes in the placenta and fetal liver (P<0.05), mainly by accelerating the maternal energy metabolism during pregnancy. However, maternal serum biochemical indices, antioxidant indices, and pathological damage to the liver and placenta predicted that the mother would be at greater health risks during this period. Moreover, transcriptomics results indicated that the differentially expressed (DE) circRNAs in the placenta regulate the maternal multiple metabolic pathways and the placental nutrient transport efficiency by sponging miRNAs and forming growth factors and proteins, ultimately improving the maternal reproductive performance. In addition, we verified the reliability of the sequencing results using reverse transcription polymerase chain reaction and identified the possibility of DE circRNAs binding to nutrient transporter genes using targeting relationship prediction. Finally, we constructed a correlation network that regulates maternal placental nutrient transport based on DE circRNAs, targeted miRNAs and nutrient transport-related genes. This study will provide scientific dietary guidance for pregnant women and new research ideas for preventing and treating pregnancy complications.