Thrombin-Induced Decidual Colony-Stimulating Factor-2 Promotes Abruption-Related Preterm Birth by Weakening Fetal Membranes

Molecular Changes on Maternal–Fetal Interface in Placental Abruption—A Systematic Review

“…As a result of the described procedure, 22 articles that met all the inclusion criteria were retrieved [ 20 , 21 , 27 , 29 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Extracted data included in this systematic review are collected in Table S2 .…”

“…In 11 articles, the effect in placental abruption was marked as “possible”, as the research was conducted in cell culture or a model and there were no samples from patients with placental abruption. In several studies [ 21 , 27 , 42 , 49 , 50 , 51 , 52 , 54 , 55 ], the researchers treated the samples (endometrial cells, placental samples, decidual cells or decidual cell cultures, fetal membranes or fetal membrane models, amnion cell cultures, human endothelial endometrial cell cultures, myometrial samples or myometrial cell samples) with THR and studied the molecular effects of this intervention. We have included these studies, as they may be considered the models of a situation actually occurring in the case of placental abruption.…”

“…During placental abruption, the decidua is exposed to bleeding-derived clotting factors, thrombin (THR, F2) being one of the most abundant [ 27 , 54 , 55 ] and best examined. THR is a serine proteinase [ 62 ] and the main effector protease of coagulation [ 21 ].…”

“…According to Kumar et al (2011) [ 49 ] and Lockwood et al (2012) [ 27 ], THR also exerted an indirect weakening effect on FM via choriodecidua-derived cytokines (among others IL-8 [ 27 , 42 , 71 , 72 ]), unidentified soluble activators [ 51 ] or chemoattracted neutrophils. According to Sinkey et al (2020) [ 55 ] and Kumar et al (2014) [ 52 ] the granulocyte-macrophage colony-stimulating factor (GM-CSF, CSF2) is one of the most important mediators of this process. Interestingly, GM-CSF, a known inducer of those proteases [ 73 , 74 , 75 ], was detected only on the maternal side of FM [ 52 ] and transduced the signal from both THR and TNFα [ 55 ].…”

“…According to Sinkey et al (2020) [ 55 ] and Kumar et al (2014) [ 52 ] the granulocyte-macrophage colony-stimulating factor (GM-CSF, CSF2) is one of the most important mediators of this process. Interestingly, GM-CSF, a known inducer of those proteases [ 73 , 74 , 75 ], was detected only on the maternal side of FM [ 52 ] and transduced the signal from both THR and TNFα [ 55 ]. Decidual GM-CSF acted through a trophoblast-expressed granulocyte-macrophage colony-stimulating factor receptor (colony-stimulating factor 2 receptor or CSF2R) [ 55 ].…”