Study of the molecular mechanism regulating the trophoblast invasion process in women of Indian origin

Objectives: The purpose of this study was to compare the transcriptional and translational levels of Matrix Metalloproteinases (MMPs) 2, 9, Tissue Inhibitors of Metalloproteinases (TIMPs) 1, 2, Cystathionine β-synthase (CBS), Specificity Protein 1 (Sp1), and MicroRNA (miR) 22 in subjects with early onset preeclampsia and normotensive, non-proteinuric controls. Methods: According to ACOG criteria, normotensive, non-proteinuric pregnant women (n = 50) from the Department of Obstetrics and Gynaecology at AIIMS, New Delhi, were enrolled as controls, while EOPE women (n = 50) following clinical diagnosis were enrolled as cases. To ascertain the expression and levels of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1, and miR-22, 5 millilitres of venous blood were drawn from each woman who was enrolled. Thirty placentae delivered by cesarean section (15 from EOPE patients and 15 from controls) were gathered in order to examine the expression and levels of the previously indicated markers. STATA 14 and Graph Pad Prism 8 were used to analyse the data. Results: In contrast to controls, EOPE patients showed significantly lower mRNA and protein expression/levels of MMPs 2, 9, CBS, and Sp1, while TIMP-1 and TIMP-2 expression/levels were elevated. In contrast, early-onset preeclamptic patients showed significantly higher gene expression of miR-22. Additionally, MMP-2 and MMP-9 gelatinolytic activity was shown to be markedly decreased in EOPE placentae. Conclusion: This is the first study of its kind to suggest that the EOPE patients' insufficient trophoblastic invasion may be caused by downregulation of MMPs 2, 9, CBS, and Sp1 and concurrent upregulation of TIMPs 1, 2, and miR-22 in the placentae obtained at delivery and the circulating blood obtained at diagnosis when compared to controls. Our study population's patients may have had faulty trophoblast invasion, a defining feature of preeclampsia, as a result of these markers' aberrant functioning.