The role of angiogenic factors in first trimester pregnancy losses

Abstract

Objective: A good blood supply towards the peri-implantation endometrium is an essential requirement for pregnancy. Intermedin (IMD), vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS), are angiogenic and vasoactive agents that play contributory roles in endometrial vascularity. The goal of this study was to immunohistochemically investigate the roles of various vasoactive factors in first trimester pregnancy losses. Materials and Methods: This was a prospective case-controlled study carried out on decidual and placental tissue samples obtained from women with unwanted pregnancies who served as the control group (n=10), and those with missed abortions who were the “missed abortion group”(n = 10). Immunohistochemistry techniques were used to compare IMD, receptor activity modifying protein (RAMP)1, RAMP2, RAMP3, VEGF, and eNOS expression of decidual and placental cells. Immunostaining for these factors was evaluated semiquantitatively by H-score analysis. Results: IMD and RAMPs in decidual cells exhibited higher expression in the control group. However, IMD and RAMP2 had a stronger expression in placental cells in the missed abortion group. In the control group, VEGF and eNOS had a higher expression in decidual cells and on the placental side, especially in syncytiotrophoblasts and cytotrophoblasts. Conclusion: Expressions of vasoactive agents, such as IMD, VEGF, and eNOS, decrease in first trimester pregnancy losses. Additionally, a compensatory mechanism against decreased endometrial and subendometrial vascularity results in the death of the embryo/fetus enhances in missed abortion cases. This mechanism characterized by increased expressions of IMD and RAMP2 initially begins in the syncytiotrophoblasts and cytotrophoblasts.