Invasive Extravillous Cytotrophoblasts Research Articles

Type 2 cadherins in the human endometrium and placenta: their putative roles in human implantation and placentation.

The cadherins are a gene superfamily of calcium-dependent cell adhesion molecules. To date, the role(s) of the cadherins in human implantation remains poorly defined. The spatiotemporal expression of the type 2 cadherins, known as cadherin-11 and cadherin-6, in the endometrium and placenta was examined using the reverse transcriptase-polymerase chain reaction. Cadherin-6 and cadherin-11 are differentially expressed in the endometrial stroma during the menstrual cycle. The switch between cadherin-6 and cadherin-11 expression in the endometrial stroma occurs during the late secretory phase. Maximum cadherin-11 mRNA levels were observed in the decidua of early pregnancy but were markedly reduced at term. In the placenta, cadherin-11 is expressed in the syncytial trophoblast and extravillous cytotrophoblast columns. However, cadherin-6 seems to be the predominant cadherin subtype present in highly invasive extravillous cytotrophoblasts. Cadherin-11 and cadherin-6 may play a central role in the formation and organization of the human endometrium and placenta.

Homeobox gene HB24, a regulator of haematopoiesis, is a candidate for regulating differentiation of the extra-embryonic trophoblast cell lineage.

Expression of the human homeobox gene HB24 in the cytotrophoblast stem cell population in first-trimester human placenta was investigated. HB24 expression was downregulated after cytotrophoblast had differentiated into syncytiotrophoblast. Expression of HB24 was also detected in first-trimester invasive extravillous cytotrophoblast cells. In term placenta, HB24 expression was detected in residual cytotrophoblast cells and in syncytiotrophoblast. Northern analysis revealed two HB24 transcripts in first-trimester placenta of approximately 2.5 kb and 5.3 kb. Ribonuclease protection assays were used to confirm expression of HB24 in first-trimester and term placenta and also to provide evidence that HB24 is downregulated in choriocarcinoma cell lines. In addition to being required for differentiation of the haematopoietic cell lineage, HB24 may be required for differentiation of the extra-embryonic trophoblast cell lineage.

Nitric oxide in vasodilator actions of ATP in the human term placenta in vitro

To summarize the recent knowledge on the implications of placenta and cytokines in normal and preeclamptic pregnancies.A literature search was conducted of applicable articles related to interactions between trophoblast and cytokines in generating preeclampsia.The initiating event in preeclampsia has been postulated to be the reduced uteroplacental perfusion as a result of abnormal extravillous cytotrophoblast invasion and remodeling of the uterine spiral arteries. Focal ischemia and hypoxia, deportation of hypoxemic trophoblast cells and abnormal expression of various placental biologic molecules, particularly the cytokines, are thought to lead to widespread dysfunction of the maternal vascular endothelium resulting in overproduction of endothelin and thromboxane, enhanced vascular sensitivity to angiotensin II, and reduced secretion of vasodilators such as nitric oxide and prostacyclin. These alterations, in turn, cause hypertension, proteinuria and edema, and pathologies in many organ systems (kidney, lung, liver, brain).

Expression of the antigen recognized by mAb GB36 in normal skin and in skin tumours

GB36, a mouse monoclonal antibody (mAb) raised against an epithelial antigen of the human trophoblast, reacts with the epithelial basement membrane of chorionic villi; it does not react with the invasive extravillous cytotrophoblast. Expression and characterization of the antigen of GB36 (designated GBA36) were investigated in normal keratinocytes by immunoprecipitation, immunofluorescence and immunoelectron microscopic studies. Immunoprecipitation experiments demonstrated that the proteins identified on keratinocytes by mAb GB36 and a rat mAb anti-integrin alpha 6 (GoH3) were the same. Using immunofluorescence and immunoelectron microscopic methods, GBA36 was localized on the cell membrane facing the epithelial basal lamina of basal keratinocytes. GBA36 distribution in benign and malignant skin tumours was evaluated by immunostaining methods (immunofluorescence and immunoperoxidase). Analysis of tumours revealed that whereas benign epithelial tumours and intradermal naevi displayed high levels of GBA36, the expression of this antigen decreased progressively in spinocellular and basal cell carcinomas, and in cutaneous melanomas in relation to invasiveness. During cell transformation, GBA36 undergoes quantitative alterations, and expression is down-regulated. Although the functional relevance of these changes remains unknown, the correlation of decreased GBA36 expression with tumour progression may indicate a role for altered integrin expression in tissue invasion by human skin carcinoma and melanoma.