Expression Profile of MicroRNAs and mRNAs in Human Placentas From Pregnancies Complicated by Preeclampsia and Preterm Labor

Abstract

MicroRNAs (miRNAs) have emerged as key regulators of gene expression stability implicated in cell proliferation, apoptosis, and development, whereas their altered expression has been associated with various pathological disorders. The objective of this study was to assess the expression profile of miRNAs and their predicted target genes in placentas from patients with preeclampsia (PC) and preterm (PT) labor as compared to normal term (NT) pregnancies. Using microarray profiling of 820 miRNAs and 18,630 mRNA transcripts, the analysis indicated that 283 of these miRNAs and 9119 mRNAs were expressed in all placentas, of which the relative expression of 20 miRNAs (P < .05 and ≥ 1.5-fold) and 120 mRNAs (P < .05, and 2-fold cutoff) was differentially expressed in PT and PC as compared to NT. The expression of miR-15b, miR-181a, miR-200C, miR-210, miR-296-3p, miR-377, miR-483-5p, and miR-493 and a few of their predicted target genes: matrix metalloproteinases (MMP-1, MMP-9), a disintegrin and metalloproteinase domains (ADAM-17, ADAM-30), tissue inhibitor of metalloproteinase 3 (TIMP-3); suppressor of cytokine signaling 1 (SOCS1); Stanniocalcin (STC2); corticotropin-releasing hormone (CRH), CRH-binding protein (CRHBP); and endothelin-2 (EDN2) were validated in these cohorts using real-time polymerase chain reaction (PCR), some displaying an inverse correlation with the expression of their predicted target genes. Functional analysis indicated that the products of these genes regulate cellular activities considered critical in normal placental functions and those affected by PC and PT labor. In conclusion, the results provide further evidence that placentas affected by PC and PT labor display an altered expression of a number of miRNAs with potential regulatory functions on the expression of specific target genes whose altered expression and function have been associated with these pregnancy complications.

Extracellular Nucleic Acids in Maternal Circulation as Potential Biomarkers for Placental Insufficiency

“…Hu et al (2009) performed a highthroughput miRNA microarray study and revealed significantly increased levels of 7 miRNAs (miR-16, miR-29b, miR-195, miR-26b, miR-181a, miR-335, and miR-222) in placentas derived from pregnancies with severe PE, occurring after 34 weeks, compared with those derived from healthy controls. (Zhu et al, 2009;Enquobahrie et al, 2011;Mayor-Lynn et al, 2011;Zhang et al, 2011). Enquobahrie et al (2011) further confirmed the downregulation of previously identified miRNA candidates (miR-1, miR-328, miR-139-5p, miR-500, and miR-1247) and found two novel miRNA candidates to be downregulated in pregnancies complicated by PE (miR-584 and miR-34c-5p).…”

MicroRNA‐181a Regulates Local Immune Balance by Inhibiting Proliferation and Immunosuppressive Properties of Mesenchymal Stem Cells

“…We previously reported that miR-181a expression was significantly increased in placental samples from women with severe PE [18]. This result was confirmed in two subsequent reports [19,20]. miR-181a is strongly expressed in bone marrow (BM) and thymus, can modulate hematopoietic lineage differentiation, and has an important role during T-and B-cell development [21][22][23].…”

How Micrornas Affect the Expression of Human Leukocyte Antigeng in Pregnancy

“…One specific microRNA found in all three studies is miR-210 (Mayor-Lynn et al, 2011;Pineles et al, 2007;Zhu et al, 2009). In two studies, miR-210 was found to be increased by a three-fold in (severe) pre-eclampsia, while Lynn and coworkers found a small downregulation.…”

“…Several studies aimed to identify miRNAs involved in pre-eclampsia by comparing miRNA expression between normal and pre-eclamptic placentas (Mayor-Lynn et al, 2011;Pineles et al, 2007;Zhu et al, 2009). Each study found various miRNAs that were either up-or downregulated in pre-eclamptic placentas.…”