Abnormal Trophoblast Invasion in Early-Onset Preeclampsia: The Involvement of Cystathionine β-Synthase, Specificity Protein 1 and microRNA-22

Objectives: To determine and compare the expression of matrix metalloproteinases (MMPs) 2, 9, tissue inhibitors of metalloproteinase (TIMPs) 1, 2, cystathionine β-synthase (CBS), specificity protein 1 (Sp1), and microRNA-22 (miR-22) in the early-onset preeclampsia (EOPE) patients and normotensive controls at both transcriptional and translational levels. Methods: The study was carried out on EOPE women (n=50) as cases, and normotensive, non-proteinuric pregnant women (n=50) as controls, enrolled at the Department of Obstetrics and Gynaecology. Expression/levels of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1, and miR-22 were determined in venous blood. Thirty cesarean-delivered placentae (15 each of EOPE patients and controls) were collected to analyze the expression/levels of the markers in the tissue. Results: Significantly reduced mRNA and protein expression/levels of MMPs 2, 9, CBS, and Sp1, whereas elevated levels of TIMP-1 and TIMP-2 were observed in EOPE participants as compared to controls. The gene expression of miR-22 was found to be significantly upregulated in EOPE participants compared with controls. Conclusions: This is the first study of its kind, which implies that insufficient trophoblastic invasion may be because of downregulation of MMPs 2, 9, CBS, Sp1, and concomitant upregulation of TIMPs 1, 2, both in the placentae collected at delivery and the circulating blood collected at diagnosis. The regulation of Sp1 by miR-22 in the EOPE participants as compared to controls was also evident by the expression of miR-22 assayed in the same set of samples.