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

Abstract

Abstract. 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 (miR-6, -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 transcription-quantitative polymerase chain reaction. The expression of miR-21 was observed to be elevated in macrosomic placenta compared with control samples, while miR-143 expression was significantly lower than in control placenta (P<0.05). No significant differences were identified in the miR-16 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 miR-21 expression quartile: Q2, odds ratio (OR)=6.67 [95% confidence interval (CI), 1.39-32.05]; Q3, OR=4.10 (95% CI, 0.88-19.11); Q4, OR=16.19 (95% CI, 2.46-106.68). Conversely, higher levels of miR-143 expression were protective against macrosomia: Q2, OR= 0.22 (95% CI, 0.049-0.98); Q3, OR= 0.11 (95% CI, 0.024-0.55), and Q4, OR= 0.16 (95% CI, 0.032-0.79). Thus, statistical analysis demonstrated that high levels of miR-21 expression and low levels of miR-143 expression predict the risk for macrosomia, indicating an interaction between the two miRNAs. Bioinformatic analysis suggested that they are likely to function in the mitogen-activated 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.

Exosomes of pasteurized milk: potential pathogens of Western diseases

“…Two independent studies confirmed increased expression of miR-21 in placenta tissue of infants born with macrosomia (birth weight > 4000 g) [99,100]. Milk miR-21, a signature miR of commercial dairy milk and cargo of bovine milk exosomes [71,72,80], most likely reaches the placenta and increases placental and trophoblast growth.…”

Whole transcriptome expression profiles in placenta samples from women with gestational diabetes mellitus

“…Downregulation of miR‐143 mediated the metabolic transition from oxidative phosphorylation to aerobic glycolysis in GDM placentas, whereas overexpression of miR‐143 increased mitochondrial respiration and mitochondrial complex expression, and decreased the expression of glycolytic enzymes 52 . Furthermore, miR‐143 might play a role in the mitogen‐activated protein kinase signaling pathway associated with macrosomia 53 . The expression level of miR‐518d in GDM placentas was significantly higher, and high expression of miR‐518d was negatively correlated with peroxisome proliferator‐activated receptor‐α, which might participate in the occurrence of GDM by regulating expression 54 .…”

The Role of miRNAs as Biomarkers for Pregnancy Outcomes: A Comprehensive Review

“…To investigate the relationship between placental-specific miRNAs and pregnancy outcomes, researchers compared the expression of miRNAs isolated from the placentas between patients affected by the disorders and healthy controls [ 8 , 51 , 54 , 56 – 58 ]. Since placental tissues are obtained at the time of delivery, it is unclear whether the aberrant miRNA expression is the cause or the consequence of the disorder.…”

“…The suitable approach, mostly used, was to identify disease-related differences in miRNA expression by miRNA microarray or second-generation sequencing in small subgroups, followed by the validation by qRT-PCR on a larger sample size [ 8 , 9 , 13 , 14 , 16 , 23 – 25 , 31 , 34 , 53 , 58 ]. However, other studies just used qRT-PCR techniques to validate candidate biomarkers identified through literature search or based on previous findings [ 10 , 11 , 18 , 26 , 51 , 52 , 54 , 55 , 57 ]. In addition, variability between studies was also observed in data reporting.…”

“…In fact, further analysis on serum of 16 pregnant women suffering from PE showed that miR141-3p and miR200c-3p were downregulated in women with fetal macrosomia, also when compared to those in preeclamptic woman, whereas miR-523-3p did not show a significant difference between the two groups [ 53 ]. In 2016, a study on placental expressed miRNAs on 67 samples of macrosomic placental tissues and 64 normal placental tissues showed that high levels of miR-21 and low levels of miR-143 are associated with macrosomia [ 54 ]. MiR-21 was also found associated to macrosomia by Jiang and colleagues; however, findings of this study on maternal serum showed that levels of miR-21 were significantly lower in serum of women delivering macrosomic infants when compared to healthy controls [ 17 ].…”