Omics Approaches to Study Formation and Function of Human Placental Syncytiotrophoblast

Abstract

Proper development of the placenta is vital for pregnancy success. The placenta regulates exchange of nutrients and gases between maternal and fetal blood and produces hormones essential to maintain pregnancy. The placental cell lineage primarily responsible for performing these functions is a multinucleated entity called syncytiotrophoblast. Syncytiotrophoblast is continuously replenished throughout pregnancy by fusion of underlying progenitor cells called cytotrophoblasts. Dysregulated syncytiotrophoblast formation disrupts the integrity of the placental exchange surface, which can be detrimental to maternal and fetal health. Moreover, various factors produced by syncytiotrophoblast enter into maternal circulation, where they profoundly impact maternal physiology and are promising diagnostic indicators of pregnancy health. Despite the multifunctional importance of syncytiotrophoblast for pregnancy success, there is still much to learn about how its formation is regulated in normal and diseased states. 'Omics' approaches are gaining traction in many fields to provide a more holistic perspective of cell, tissue, and organ function. Herein, we review human syncytiotrophoblast development and current model systems used for its study, discuss how 'omics' strategies have been used to provide multidimensional insights into its formation and function, and highlight limitations of current platforms as well as consider future avenues for exploration.

Keywords: cell models; omics; placenta; pregnancy; syncytiotrophoblast; trophoblast.

FIGURE 1

Sequential development of STB. (A) Progression of a human embryo at approximately gestational days 7–8 (peri-implantation; left image) and days 9–10 (post-implantation; right image). Please note the invasive properties of the primitive STB at the forefront of the implanting human embryo and the gradual development of blood-filled lacunae. (B) Cross section of a chorionic villus in later gestation. Please note that the STB layer exhibits apical-basal polarity (as shown by the presence of microvilli) and bathes directly in maternal blood. An extruding syncytial knot is also shown. The villus core contains blood vessels that connect to the fetal circulation, as well as different cell types (such as Hofbauer cells and fibroblasts). CTBs are shown in various stages of their life cycle (proliferating, differentiating, and fusing).

FIGURE 2

Schematic showing multiple omics approaches that have been used to make new discoveries about STB biology.

FIGURE 3

Schematic illustrating the multifunctional importance of STB for healthy pregnancy. A cross section of a chorionic villus near term is shown. O₂, micronutrients, immunoglobulins, water, and various other substances pass across the STB layer to gain access to blood vessels in the villus core, through which they can be carried to the fetus. CO₂ and waste products diffuse across the STB layer from fetal to maternal blood. STB also produces and secretes a variety of factors into maternal blood, including peptide and steroid hormones, growth factors, EVs, and larger vesicles (e.g., syncytial knots). Given the diverse functions of STB for pregnancy success and its contiguity with maternal blood, aberrant STB function can contribute to adverse pregnancy outcomes.