Intersection of regulatory pathways controlling hemostasis and hemochorial placentation
Masanaga Muto, Damayanti Chakraborty, Kaela M. Varberg, Ayelen Moreno‐Irusta, Khursheed Iqbal, Regan L. Scott, Ross McNally, Ruhul Choudhury, John Aplin, Hiroaki Okae, Takahiro Arima, Shoma Matsumoto, Masatsugu Ema, Alan E. Mast, Elin Grundberg, Michael J. Soares
Abstract
rat models revealed critical roles for TFPI in embryonic development, resulting in homogeneous midgestation lethality prohibiting analysis of the role of TFPI as a regulator of the late-gestation wave of intrauterine trophoblast cell invasion. In vivo trophoblast-specific TFPI knockdown was compatible with pregnancy but had profound effects at the uterine-placental interface, including restriction of the depth of intrauterine trophoblast cell invasion while leading to the accumulation of natural killer cells and increased fibrin deposition. Collectively, the experimentation implicates TFPI as a conserved regulator of invasive/EVT cell development, uterine spiral artery remodeling, and hemostasis at the maternal-fetal interface.