Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer. Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.

In China, premature rupture of membranes (PROM) counts as a major pregnancy complication in China and usually results into adverse pregnancy outcomes. We analysed the vagina microbiome composition using 16S rDNA V3–V4 amplicon sequencing technology, in this prospective study of 441 women in their third trimester of pregnancy. We first divided all subjects into PROM and HC (healthy control) groups, in order to investigate the correlation of vagina microbiome composition and the development of PROM. We found that seven pathogens were higher in the PROM group as compared to the HC group with statistical significance. We also split all subjects into three groups based on Lactobacillus abundance-dominant (Lactobacillus > 90%), intermediate (Lactobacillus 30–90%) and depleted (Lactobacillus < 30%) groups, and explored nine pathogenic genera that were higher in the depleted group than the intermediate and dominant groups having statistical significance. Finally, using integrated analysis and logistics regression modelling, we discovered that Lactobacillus (coeff = −0.09, p = 0.04) was linked to the decreased risk of PROM, while Gardnerella (coeff = 0.04, p = 0.02), Prevotella (coeff = 0.11, p = 0.02), Megasphaera (coeff = 0.04, p = 0.01), Ureaplasma (coeff = 0.004, p = 0.01) and Dialister (coeff = 0.001, p = 0.04) were associated with the increased risk of PROM. Further study on how these pathogens interact with vaginal microbiota and the host would result in a better understanding of PROM development.

Premature rupture of membranes (PROM) is usually associated with pregnant and neonatal complications. Most of the PROM cases are caused by ascending asymptomatic genital infection. In China, PROM (15.3%) is more common than spontaneous preterm labor (7.3%) and leads to more adverse pregnancy outcomes. Here, we designed a prospective cohort study to measure the metabolomics changes in vaginal swab samples and explored their potential contribution to PROM. A total of 260 differentially expressed metabolites were identified and further analyzed. In the PROM group, N-acetyl-d-galactosamine and sucrose were downregulated (P = 0.0025, P = 0.0195, respectively), both of which are the upstream metabolites of the glycolysis pathway. Furthermore, estriol 3-sulfate 16-glucuronide (P = 0.0154) and 2-methoxy-17beta-estradiol 3-glucosiduronic acid (P = 0.004), two final metabolites in steroid hormone biosynthesis, were both downregulated in the PROM group. Finally, we found two catechin metabolites (epigallocatechin-7-glucuronide, P = 0.0009; 4′-methyl-epigallocatechin-7-glucuronide, P = 0.01) as well as DL-citrulline (P = 0.0393) were also significantly downregulated in the PROM group compared with the healthy control (HC) group, which are related to important antioxidant and anti-inflammatory activities in the human body. Altogether, metabolite changes in glycolysis, steroid hormone biosynthesis, and antioxidant/anti-inflammatory pathways may contribute to (or be a consequence of) vaginal dysbiosis and PROM. Metabolite pathway analysis is a new and promising approach to further investigate the mechanism of PROM and help prevent its unfavorable pregnant outcomes at a functional level. Trial registration number: ChiCTR2000034721