Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia.

Macrosomia, a birth weight ≥ 4,000 g, is associated with maternal and infant health problems. The dysregulation of microRNAs (miRNAs) in the placenta is associated with adverse birth outcomes, yet whether aberrantly expressed placental miRNAs are associated with macrosomia remains unknown. The aim of the current study was to characterize the expression of three placental miRNAs (miR­6, ­21 and ­143) and evaluate their association with macrosomia. The miRNA expression in placental tissues from 67 macrosomic pregnancies and 64 normal pregnancies were analyzed using reverse transcription­quantitative polymerase chain reaction. The expression of miR­21 was observed to be elevated in macrosomic placenta compared with control samples, while miR­143 expression was significantly lower than in control placenta (P<0.05). No significant differences were identified in the miR­16 expression levels between the groups (P=0.955). Following division of miRNA expression levels by quartile, logistic regression models demonstrated that the odds of macrosomia increased with miR­21 expression quartile: Q2, odds ratio (OR)=6.67 [95% confidence interval (CI), 1.39­32.05]; Q3, OR=4.10 (95% CI, 0.88­19.11); Q4, OR=16.19 (95% CI, 2.46­106.68). Conversely, higher levels of miR­143 expression were protective against macrosomia: Q2, OR=0.22 (95% CI, 0.049­0.98); Q3, OR=0.11 (95% CI, 0.024­0.55), and Q4, OR=0.16 (95% CI, 0.032­0.79). Thus, statistical analysis demonstrated that high levels of miR­21 expression and low levels of miR­143 expression predict the risk for macrosomia, indicating an interaction between the two miRNAs. Bioinformatic analysis suggested that they are likely to function in the mitogen­activated protein kinases signaling pathway to influence the risk of macrosomia. The results of the present study provide evidence that placental miR-21 and -143 are important in the formation of macrosomia.

Birth weight is associated with placental fat mass- and obesity-associated gene expression and promoter methylation in a Chinese population.

OBJECTIVE: To explore the relationship between birth weight and fat mass- and obesity-associated (FTO) gene expression and promoter methylation status in the Chinese population. METHODS: Seventy-five neonates and their mothers were recruited from Yuying Children's Hospital of Wenzhou Medical University. Subjects were divided into three groups by birth weight: low (< 3,500 g, n = 20), medium (3,500-3,999 g, n = 30) and high (≥ 4,000 g, n = 25). Placental FTO transcript levels and promoter methylation were determined by quantitative PCR and Sequenom MassARRAY®. RESULTS: Placental FTO mRNA expression was significantly increased in the high- and medium-weight groups compared to the low-weight group (p = 0.023). Methylation rates of CpG11 sites were significantly decreased in high-birth weight newborns (p = 0.018). Multiple linear regressions showed placental FTO mRNA, maternal pre-pregnancy body mass index (BMI) and CpG11 methylation rate were independently associated with increased fetal birth weight. Additionally, FTO mRNA expression was negatively associated with CpG6.7.8.9 methylation in mothers that underwent C-section. CONCLUSIONS: High placental FTO expression is associated with increased birth weight in Chinese neonates, and FTO promoter methylation level at a specific CpG site is negatively associated with birth weight. Further work is needed to determine the functionality of this CpG site in placentas.