Genetic Variants in Preeclampsia: Lessons From Studies in Latin-American Populations

Abstract

Placental vascularization is a tightly regulated physiological process in which the maternal immune system plays a fundamental role. Vascularization of the maternal-placental interface involves a wide range of mechanisms primarily orchestrated by the fetal extravillous trophoblast and maternal immune cells. In a healthy pregnancy, an immune cross-talk between the mother and fetal cells results in the secretion of immunomodulatory mediators, apoptosis of specific cells, cellular differentiation/proliferation, angiogenesis, and vasculogenesis, altogether favoring a suitable microenvironment for the developing embryo. In the context of vasculopathy underlying common pregnancy disorders, it is believed that inefficient invasion of extravillous trophoblast cells in the endometrium leads to a poor placental blood supply, which, in turn, leads to decreased secretion of angiogenic factors, hypoxia, and inflammation commonly associated with preterm delivery, intrauterine growth restriction, and preeclampsia. In this review, we will focus on studies published by Latin American research groups, providing an extensive review of the role of genetic variants from candidate genes involved in a broad spectrum of biological processes underlying the pathophysiology of preeclampsia. In addition, we will discuss how these studies contribute to fill gaps in the current understanding of preeclampsia. Finally, we discuss some trending topics from important fields associated with pregnancy vascular disorders (e.g., epigenetics, transplantation biology, and non-coding RNAs) and underscore their possible implications in the pathophysiology of preeclampsia. As a result, these efforts are expected to give an overview of the extent of scientific research produced in Latin America and encourage multicentric collaborations by highlighted regional research groups involved in preeclampsia investigation.

Data-Driven Modeling of Pregnancy-Related Complications

“…Pregnancy occurs against the genetic background and epigenetic programming of both the mother and the fetus. Maternal genetic variants affect the success of essential developmental processes such as decidualization and placentation, whereas both maternal and fetal genetics play a role in maintaining the delicate immune balance that characterizes embryonic and fetal development [68][69][70]. While genetic contributions to different complications in pregnancy are probably polygenic, genome-wide association studies (GWASs) have found genetic variants associated specifically with sPTB, illustrating how a mother's genetic makeup can set the stage for fetal development and pregnancy outcome even before conception [71][72][73].…”

Influence of NKG2C gene deletion and CCR5Δ32 in Pre‐eclampsia—Approaching the effect of innate immune gene variants in pregnancy

“…Pre‐eclampsia (PE) is a hypertensive disorder that affects 2%–8% of all pregnant women (Duley, ). PE is a polygenic disorder resulting from both foetal/placental and maternal genetic contributions and manifests as a complex phenotype (Michita, Kaminski, & Chies, ; Triche et al, ). In pathophysiological terms, PE is characterized by de novo hypertension after 20 weeks of gestation combined with proteinuria (Duley, ; Mol et al, ).…”

Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia

“…This allowed the determination of RNA levels but not protein levels. Another limitation is that RNA microarrays are unable to reveal the expression of polymorphic gene variants, which may have a role on preterm preeclampsia [115,116]. In future studies, next-generation sequencing may help reveal these variants.…”