They are the specialized cells of the placenta; they play a significant role in the implantation and formation of the maternal-fetal interface.
Through an unusual differentiation process examined in this review, these fetal cells acquire properties of leukocytes and endothelial cells that allow many of their specialized functions.
In recent years, much has been learned about the regulatory mechanisms, from the transcriptional networks to the oxygen tension, which controls the differentiation of the trophoblast. The challenge is to convert this information into clinically useful tests to maintain placental function and, therefore, pregnancy outcome.
Importance of syncytiotrophoblast formation
They enter the maternal endometrium and must exhibit invasive properties to form an effective maternal-fetal vascular relationship. However, excessive invasiveness of the trophoblast cells can cause too much stress in the uterus, leading to uterine bleeding and prompting an immune response against the embryo.
Although the uterine endometrium has the means to control the invasion of the trophoblast, the trophoblasts themselves may have evolved to limit their invasiveness in the uterine endometrium. One of these mechanisms seems to be slowing down transit through cell cycles.
The inhibition of cell cycles causes endoreduplication, forming giant trophoblastic cells. In humans and marine species, syncytiotrophoblasts are created through the fusion of cytotrophoblastic cells, resulting in the cessation of cell cycles and the regulation of trophoblast invasion of the maternal endometrium.
Syncytization may not be the only mechanism by which trophoblasts control their invasiveness. It is known that Hyrax has memorial placentation, but its trophoblasts do not form a syncytium. This independent appearance of similar functions on different sides is an excellent example of convergent evolution.
Spontaneous trophoblastic cell lines, immortalized and transformed
The trophoblast cell lines have become an invaluable tool for studying various aspects of trophoblast biology. These cell lines are more resistant when compared to primary trophoblastic cell cultures, including prolonged lifetimes in culture.
Therefore, they are advantageous for more detailed investigations of trophoblast function and molecular biology studies. Trophoblast cell lines can be established from primary cultures by random selection in vitro or by ectopic expression of oncoproteins that confer immortality.
Choriocarcinoma cells are transformed populations of trophoblast cells that readily adapt to in vitro conditions. However, the data obtained from these manipulated or altered cell lines must be interpreted with caution due to these features.
These trophoblast cell lines have been removed from their environment in vivo during many passages and may be distorted in some of their properties.
However, they are commonly used as a convenient and valuable resource to provide information on the function of the trophoblast. A list of widely used human trophoblast cell lines is provided in the table.
Trophoblastic proliferations may present problems in the differential diagnosis with high-grade endometrioid carcinoma, squamous cell carcinoma, and CDs containing trophoblastic cells.
The trophoblastic tumor of the placental site is composed of intermediate trophoblastic cells characterized by medium to large mononuclear cells or, rarely, multinucleated cells showing enlarged nuclei and prominent nucleoli.
Valuable features include finding neoplastic cells that replace the vascular walls associated with fibrinoid necrosis and the division of muscle fibers by tumor cells. Keratin and EMA are not helpful in the differential diagnosis between CD and placental site trophoblastic tumor.
However, the latter is also favorable for alpha-inhibin, hPL, CD146, and hCG. Finally, these patients have elevated serum levels of hCG in approximately 50% of cases.
The other trophoblastic proliferation that can be confused with a poorly differentiated endometrioid ES or a squamous cell carcinoma is the epithelioid trophoblastic tumor.
This neoplasm is characterized by a proliferation of intermediate trophoblastic cells originating from the chorionic trophoblast. The nests of mononuclear cells with clear to eosinophilic cytoplasm are frequently distributed around the blood vessels without invading the vessel walls.
Distinctive morphological features include extensive hyaline-like necrosis with well-defined geographic distribution and margins.
Keratin and EMA are not helpful in the differential diagnosis between epithelioid trophoblastic tumors and EC. However, the epithelioid trophoblastic tumor is favorable for alpha-inhibin and p63 and is focally positive for HPV, hCG, and CD116.
Choriocarcinoma is easy to distinguish from CD because it typically shows biphasic growth, with mononuclear cells surrounded by syncytiotrophoblast cells. However, it should be noted that choriocarcinoma can be seen in association with endometrioid CE.
Gestational trophoblastic diseases
The diseases of the gestational trophoblast are a rarity in human biology. A hydatidiform mole is what happens, for example, when two male gametes and their haploid chromosomal components form a pregnancy.
The formed zygote is not differentiated correctly, leading to a pregnancy comprising most of the placental tissue.
The hydatidiform mole can be invasive, attacking the uterus and associated organs. The normal tissue of the placenta and the tissue of the hydatidiform mole can become a type of malignancy. This is known as gestational trophoblastic neoplasia (GTN).