Laminins Regulate Placentation and Pre-eclampsia: Focus on Trophoblasts and Endothelial Cells

Abstract

Pre-eclampsia is a systemic vascular disease characterized by new-onset hypertension and/or proteinuria at ≥20 weeks of gestation and leads to high rates of maternal and perinatal morbidity and mortality. Despite the incomplete understanding of pre-eclampsia pathophysiology, it is accepted that insufficient spiral artery remodeling and endothelial dysfunction are major contributors. Laminins (LNs) are a vital family of extracellular matrix (ECM) molecules present in basement membranes that provide unique spatial and molecular information to regulate implantation and placentation. LNs interact with cell surface receptors to trigger intracellular signals that affect cellular behavior. This mini-review summarizes the role of LNs in placental development during normal pregnancy. Moreover, it describes how LN deficiency can lead to the pre-eclampsia, which is associated with trophoblast and vascular endothelial dysfunction. New research directions and the prospect of clinical diagnosis of LN deficiency are discussed, and the gaps in basic and clinical research in this field are highlighted.

Keywords: endothelial dysfunction; laminin; placenta; pre-eclampsia; trophoblast.

FIGURE 1

Basement membrane constituents in vessels and LN structure. (A) In blood vessels, the basement membrane separates endothelial cells from supporting cells such as pericytes and connective tissue. The basement membrane consists of LN, type IV collagen, perlecan, and nidogen. (B) LN as a trimeric protein containing five α, three β, and three γ chains; all laminin chains share a common domain structure with a number of globular and rod-like domains.

FIGURE 2

Schematic diagram illustrating the potential causes for the low level of laminins induced- pre-eclampsia: focus on trophoblasts and endothelial cells. The decreased levels of serum LN and placental LN expression (pale pink) contribute to abnormal implantation, trophoblast invasion defect, and disorder vascular endothelial factors (pale green). These pathophysiological states lead to placenta bed pathology, insufficient uterine spiral artery remodeling (blue, known as stage 1 of pre-eclampsia) and maternal systemic endothelial dysfunction (yellow, known as stage 2 of pre-eclampsia). The figure leaves open the possibility that some LNs might play the role by binding to their receptors (dotted arrow, pale pink), while the role of these receptors is clearly known (solid arrow).