Localization and Function of Factor XIII at the Fetal-Uterine Interface: Recurrent Abortion Management Issues

Abstract

The blood coagulation Factor XIII (FXIII) is a transglutaminase catalyzing γ-glytamyl ε-lysine crosslinks between various molecules. It is most known for its role in crosslinking fibrin and stabilizing the blood clot in the process of coagulation in wound healing. The Factor XIII is also essential in maintaining pregnancy, and recurrent spontaneous abortions are reported in FXIII deficient patients. The localization and the role of FXIII in the development of the placenta were investigated in this study. Preliminary, FXIII was found to be located in macrophages, and in this study we verified by immunoblotting and mass spectrometry that FXIII is present in the decidual part of the placenta. The effect of FXIII on trophoblastic invasion during placental development was also examined. The invasion process was studied with the Boyden chamber assay using both an immortalized trophoblast cell line (HTR-8/SVneo), and primary culture of extravillous trophoblasts. A significant effect of FXIII on inhibition of invasion using trophoblast cell line was found, but no effect was observed with the primary culture. The cause of the inhibition on invasion observed with the cell line was ruled out to be caused by other indirect effects of FXIII, such as cytotoxicity, effect on secretion of matrix metalloproteases and proliferation. The results showed unfortunately great variability; therefore better controls must be included in the assays in order to obtain more reliable results. Future perspectives are to optimize the existing method or to use another technique to study the more in vivo approach on invasion using primary culture. Later, it would be interesting to examine the proteomics of FXIII; to identify the molecules involved in crosslinking by FXIII in placental development. This would allow us to understand more of the physiology of FXIII and its role in placental development which could aid in recurrent abortion managements.