LncRNA Pathway Involved in Premature Preterm Rupture of Membrane (PPROM): An Epigenomic Approach to Study the Pathogenesis of Reproductive Disorders

Abstract

Preterm birth (PTB) is a live birth delivered before 37 weeks of gestation (GW). About one-third of PTBs result from the preterm premature rupture of membranes (PPROM). Up to the present, the pathogenic mechanisms underlying PPROM are not clearly understood. Here, we investigated the differential expression of long chain non-coding RNAs (lncRNAs) in placentas of PTBs with PPROM, and their possible involvement in the pathogenic pathways leading to PPROM. A total number of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas of PPROM (group A), which were compared to full-term birth (FTB) (group B), PTB (group C), and premature rupture of membrane (PROM) (group D) at full-term, respectively. Instead of investigating the individual pathogenic role of each lncRNA involved in the molecular mechanism underlying PPROM, we have focused on investigating the metabolic pathways and their functions to explore what is the likely association and how they are possibly involved in the development of PPROM. Six groups, including up-regulation and down-regulation in the comparisons of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C, 18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down-regulated in A vs. B. Functional analysis showed pathways of infection and inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton, and smooth muscle contraction are the major pathogenic mechanisms involved in the development of PPROM. Characterization of these pathways through identification of lncRNAs opened new avenues for further investigating the epigenomic mechanisms of lncRNAs in PPROM as well as PTB.

Ubiquitin-Proteasome-Collagen (CUP) Pathway in Preterm Premature Rupture of Fetal Membranes

“…The current study is a continuing investigation of the regulatory role of lncRNAs in the molecular pathogenesis of sPTB, based on our previous studies, in which we identified differential expression of lncRNAs in sPTL and PPROM (Luo et al, 2013; Pan et al, 2015). In the current study, we analyzed the DEPs of the lncRNAs and the mRNAs that are associated with the CUP pathway that may also associate with PPROM (Zhong et al, 2015).…”

Long non‐coding RNA regulation of reproduction and development

“…Similarly, a screen in women for lncRNAs associated with premature rupture of the placental membranes (PPROM) identified thirteen lncRNAs that were differentially expressed in PPROM versus full‐term placentae. These lncRNAs appear to play roles in the inflammatory response, smooth muscle contraction, and ligand‐receptor interactions (Luo et al, , ). In a third study, women suffering from polycystic ovary syndrome—characterized by high serum androgens, absence or irregular menstruation, and infertility—the lncRNAs SRAP / SRA1 and CTBP1‐AS1 (carboxy‐terminal binding protein 1, antisense transcript 1) were overexpressed compared to healthy controls (Liu et al, , ).…”

Placental transcriptome in development and pathology: expression, function, and methods of analysis

“…72 Three of these (LOC391533, LOC284100, and CEACAMP8) were validated as up-regulated in PE samples, and were suggested to play a role in lipid metabolism and angiogenesis. Another lncRNA microarray study, performed by Luo et al, 73 examined samples with preterm PROM compared to term PROM, and preterm and term control placentas, revealing preterm PROM changes in infection, inflammation, apoptosis, and signaling pathways.…”