Lee-Chuan Kao

Differentiation of Human Trophoblasts: Structure-Function Relationships

The human placenta and the chorion laeve are derived from the trophectoderm of the implanting blastocyst (1). During the process of implantation, the trophoblast cells replicate and invade into the uterine endometrium, initiating the formation of a hemochorial placenta. The trophoblast cells differentiate along several different pathways, becoming extravillous trophoblasts (sometimes called intermediate trophoblasts), extravillous multinucleated giant cells, columns of cytotrophoblasts that anchor the conceptus to the uterus, and floating chorionic villi. The chorionic villi form from avascular buds of cytotrophoblasts that develop into multilayered ramifications. The villi comprise an outer layer of syncytiotrophoblast overlying mononucleate cytotrophoblasts that are connected to each other and the syncytiotrophoblast by desmosomes. The cytotrophoblasts sit upon a basement membrane that encapsulates the villus core that contains blood vessels, macrophages, and mesenchymal elements. Each of the trophoblast phenotypes noted above displays characteristic functional properties that have been elucidated by immuno-cytochemical studies, in situ hybridization histochemistry, and analysis of isolated tissues and cells in vitro.

Human Trophoblast Differentiation

The human placenta is a dynamic organ which performs vital structural and metabolic functions during pregnancy. The trophoblastic component of this organ, which is derived from the trophectoderm of the blastocyst (1,2), is responsible for many of these specialized roles. Trophoblasts assume different morphological forms and functions during pregnancy and their phenotype appears to be linked, at least in part, to their physical location. Trophoblastic cells invading the uterus can be either mononucleate (X cells or intermediate trophoblasts; 3,4,5) or multinucleated (giant wandering cells). These cells display a distinctive pattern of gene expression which has been mapped to some extent by immunocytochemical analysis of placental bed biopsies (6,7). Trophectoderm of the implanting blastocyst which faces the uterine lumen evolves into the chorion laeve, which contains mononucleate trophoblast cells. These cells also have an unique pattern of gene expression. The chorionic villi of the placenta consist of an outer layer of syncytial trophoblast overlying a layer of mononuclear cytotrophoblasts which sit ontop of a basement membrane encapsulating the core of the villus which contains capillaries, supporting cells and macrophages (Hoffbauer cells). The functional characteristics of the cytotrophoblasts and syncytial trophoblasts differ markedly as revealed by immunocytochemical and in situ hybridization histochemistry analysis of placental tissue (8). For example, cytotrophoblasts appear to be the site of synthesis of a variety of neural peptides including somatostatin, gonadotropin releasing hormone and corticotropin releasing hormone, whereas the syncytial trophoblast is enriched in enzymes participating in steroid hormone synthesis and is the primary site of chorionic gonadotropin (CG), chorionic somatomammotropin (CS) (9,10) and variant growth hormone production.

Regulation of Trophoblast Endocrine Function: The Placenta Does Its Own Thing Transcriptionally

The placenta is the most structurally diverse mammalian organ. The remarkable variation in the morphology of the placenta across species can be rationalized by the fact that the forces that drive placental evolution are different from those that impact upon the organism in postnatal life. The placenta must serve the competing needs of the mother and fetus; evolution presumably strives to increase the efficiency of this unique symbiotic relationship. Given these considerations, it is not surprising that recent advances in molecular biology have revealed that trophoblast cells employ novel mechanisms to control the expression of specific genes (1).

Oxysterols: Regulation of Biosynthesis and Role in Controlling Cellular Cholesterol Homeostasis in Ovarian Cells

Steroid-producing cells obtain cholesterol for use in hormone synthesis by de novo synthesis from acetyl co-enzyme A or through accumulation of cholesterol from circulating lipoproteins. Tropic hormones, which augment steroidogenesis (e.g., pituitary gonadotropins acting on ovarian cells), increase both de novo sterol synthesis and lipoprotein cholesterol uptake. Recent review articles summarize the various observations documenting this regulation (1-4).