Trophoblast Stem Cells: Function in Placenta Formation

Trophoblast stem cells are the foundational cells responsible for building the placenta, an organ that supports the embryo throughout pregnancy. They are the first cell type to differentiate from the fertilized egg, appearing in humans about four days after fertilization. These cells are dedicated to creating extraembryonic structures, meaning they do not become part of the fetus itself. Their purpose is to establish a connection with the mother’s system to provide nutrients, setting the stage for a successful implantation.

Origin of Trophoblast Stem Cells

Trophoblast stem cells originate within a structure called the blastocyst, which forms approximately four to five days after fertilization. The blastocyst is a hollow sphere of cells containing the first clear division of labor in the developing embryo. It is composed of two distinct parts: an inner cluster of cells called the inner cell mass, and an outer layer known as the trophectoderm.

The inner cell mass is destined to develop into the fetus. In contrast, the trophectoderm is the exclusive source of all trophoblast lineages, and its cells are the direct precursors to trophoblast stem cells. This specialization marks the segregation of cells that will form the fetus from those that will form its support system.

Once this lineage decision is made, the trophectoderm cells are committed to their placental fate. As the blastocyst prepares for implantation, these cells proliferate to perform their function of attaching to the uterine wall. This outer layer constructs the entire fetal portion of the placenta through ongoing division and specialization.

The Process of Placenta Formation

The process of building the placenta starts with implantation into the uterine wall. Around six to seven days after fertilization, the blastocyst makes contact with the uterine lining. The trophoblast cells on the surface of the blastocyst are responsible for this initial adhesion to the endometrium. This attachment signals the beginning of a controlled invasion into the maternal tissue.

Once attached, the trophoblast cells multiply rapidly and secrete enzymes that allow them to burrow into the uterine wall. This invasion establishes a physical and biological connection between the developing embryo and the mother. As the trophoblast cells move deeper, they envelop the conceptus until it is fully embedded within the endometrium.

This burrowing action lays the groundwork for the placenta’s complex structure. The invading trophoblast cells form finger-like projections called chorionic villi—the functional units of the placenta. These villi maximize the surface area for exchange, while spaces called lacunae form within the trophoblast tissue and fill with maternal blood, allowing for nutrient transfer without direct blood mixing.

Differentiation into Specialized Trophoblasts

To construct the placenta, trophoblast stem cells differentiate into several specialized cell types. This process begins almost immediately upon implantation. The initial trophoblast layer divides into two main populations: an inner layer of individual, proliferating cells called cytotrophoblasts, and an outer, multinucleated layer known as the syncytiotrophoblast.

Cytotrophoblasts are the progenitor cells of the placenta. These actively dividing cells act as a reserve, replenishing the other trophoblast populations as the placenta grows. They form the cellular layer that surrounds the core of the placental villi. As development proceeds, many cytotrophoblasts fuse to form the overlying syncytiotrophoblast.

The syncytiotrophoblast is a continuous cell layer that covers the placenta’s surface and is in direct contact with maternal blood. This layer facilitates the exchange of gases, nutrients, and waste products. It also functions as an endocrine organ, producing hormones like human chorionic gonadotropin (hCG) to maintain the pregnancy. A third type, the extravillous trophoblast, invades the uterine wall to anchor the placenta and remodel maternal arteries.

Applications in Scientific Research

The ability to culture trophoblast stem cells in the laboratory has advanced the understanding of human development and pregnancy-related disorders. Because obtaining tissue samples from the placenta during an ongoing pregnancy is difficult and risky, these lab-grown cells provide a model to study the earliest stages of placental formation. Researchers use these models to investigate the cellular and molecular mechanisms behind successful implantation and placental function.

This research has implications for understanding and potentially treating pregnancy complications. For example, preeclampsia, a condition characterized by high blood pressure, is linked to inadequate invasion of trophoblast cells into the uterine wall. By studying trophoblast stem cells from patients with a history of preeclampsia, scientists can investigate the origins of the disorder. These models are also used to explore the causes of miscarriage and intrauterine growth restriction, as many of these issues originate from placental defects.

Beyond studying complications, trophoblast stem cells are also used to explore early human development. Scientists can convert adult cells, such as skin cells, into pluripotent stem cells and then guide them to become trophoblast stem cells. This allows for the creation of patient-specific placental models to study genetic factors that affect pregnancy success. This work may lead to new diagnostic biomarkers or therapeutic targets for infertility and pregnancy disorders.