Spontaneous labor at term is characterized by the expression of inflammasome components, which may participate in the activation of caspase-1 and lead to the cleavage and release of mature IL-1β by the chorioamniotic membranes. These results support the participation of the inflammasome in the mechanisms responsible for spontaneous parturition at term.

We propose a role for Galphai/o protein activation and subsequent interaction of Gbetagamma with PLCbeta in mediating the proapoptotic effects of ethanol upon the developing neural crest.

Background The human fetus is able to mount a systemic inflammatory response when exposed to microorganisms. This stereotypic response has been termed the “fetal inflammatory response syndrome” (FIRS), defined as an elevation of fetal plasma interleukin-6 (IL-6). FIRS is frequently observed in patients who delivered preterm associated with intra-amniotic infection (IAI), acute inflammatory lesions in the placenta, and a high rate of neonatal morbidity. Recently, a novel form of fetal systemic inflammation, characterized by an elevation of fetal plasma CXCL10, has been identified in patients with placental lesions suggestive of “maternal anti-fetal rejection”. These lesions include chronic chorioamnionitis, plasma cell deciduitis and villitis of unknown etiology (VUE). In addition, a seropositivity for HLA panel-reactive antibodies (PRA) in maternal sera can also be used as an index of suspicious for “maternal anti-fetal rejection”. The purpose of this study was to determine: 1) the frequency of pathologic evidence of “maternal anti-fetal rejection” in term and spontaneous preterm births; 2) the fetal serum concentration of CXCL10 in patients with and without evidence of maternal anti-fetal rejection; and 3) the fetal blood transcriptome and proteome in pregnancy with evidence of fetal inflammatory response associated with maternal anti-fetal rejection. Methods Maternal and fetal sera were obtained from normal term birth (N=150) and spontaneous preterm births (N=150). Fetal inflammatory response associated with maternal anti-fetal rejection was diagnosed when the patients met two or more of the following criteria: 1) presence of chronic placental inflammation; 2) ≥80% of maternal HLA class I panel-reactive antibody (PRA) seropositivity; and 3) fetal serum CXCL10 concentration > 75th percentile of normal. Maternal HLA PRA was analyzed by flow cytometry. The concentration of fetal CXCL10 and IL-6 were determined by ELISA. Transcriptome analysis was undertaken after extraction of total RNA from white blood cells with a whole-genome DASL assay. Proteomic analysis of fetal serum was conducted by two-dimensional difference gel electrophoresis. Differential gene expression was considered significant when there was a p<0.01 and a fold-change >1.5. Results 1) The frequency of placental lesions consistent with maternal anti-fetal rejection was higher in patients with preterm delivery than in those with term delivery (56% vs. 32%; P<0.001); 2) patients with spontaneous preterm births had a higher rate of maternal HLA PRA class I positivity than those who delivered at term (50% vs. 32%; P=0.002); 3) fetuses who were born to mothers with positive maternal HLA PRA results had a higher median serum CXCL10 concentration than in those with negative HLA PRA results (P<0.001); 4) the median serum CXCL10 concentration (but not IL-6) was higher in fetuses with placental lesions associated with maternal anti-fetal rejection than in those without such lesions (P<0.001); 5) a whole-genome DASL assay of fetal blood RNA demonstrated ...