フィブリンを介した初期ヒト栄養膜の成長制限は、線溶活性化により成長促進に切り替えられる

抄録

Introduction: Fibrin(ogen) plays an important role in various physiological processes and is also critical for maintaining fetal-maternal attachment during pregnancy. Fibrin has been used to increase implantation rates in human-assisted reproductive technology; however, its utility in vitro has not yet been demonstrated. 

Results: Fibrin did not affect the developmental speed or morphology of mouse blastocysts, and a large fibrin-degrading region was observed in the attachment stage. On the other hand, fibrin significantly suppressed the spreading and outgrowth of trophoblast in human blastocysts, and trophoblast grew after the appearance of small fibrin-degrading regions. uPA was identified as a fibrinolytic factor in the supernatant, and uPA activity was significantly weaker in human blastocysts than in mouse blastocysts. The inhibition of uPA significantly reduced the outgrowth of trophoblast in mouse and human blastocysts. Human blastocysts expressed PLAU (uPA), PLAUR (uPAR), SERPINE1 (PAI-1), and SERPINB2 (PAI-2), whereas mouse blastocysts were limited to Plau, Plaur, and Serpine1. In a subsequent experiment on human blastocysts, the addition of exogenous uPA and the PAI-1 inhibitor promoted trophoblast growth in the presence of fibrin, as did the addition of FDPs.

Discussion: The present results suggest that the distinct features of trophoblast spreading and outgrowth in human blastocysts observed in the presence of fibrin are regulated by a phenotypic conversion induced by contact with fibrin and FDPs. Mouse embryos did not reproduce the human phenomenon, indicating that the present results are unique to humans.