ABSTRACT
A history of previous birth of a low birthweight infant, previous cesarean sections, multiple previous spontaneous abortions, prior stillbirth, or uterine anomaly identifies women at increased risk for recurrent abortion, preterm birth, or stillbirth. We review the evidence for the potential benefit of reproductive history in identifying strategies for evaluation and treatment to prevent recurrent adverse pregnancy outcome. We offer evidence-based recommendations for management of women with these histories.
Subject(s)
Preconception Care , Pregnancy Complications/prevention & control , Reproductive History , Female , Humans , Pregnancy , Pregnancy OutcomeABSTRACT
Preterm birth is a leading cause of neonatal morbidity and mortality. Despite a growing body of evidence correlating inflammation with preterm birth, the signal transduction pathways responsible for the emptying of the uterus in the setting of intrauterine inflammation has not been elucidated. We now report a unique, reproducible mouse model of localized intrauterine inflammation. This model results in 100% preterm delivery with no maternal mortality. Using our model, we also show that platelet-activating factor is a crucial mediator of both inflammation-induced preterm birth and fetal demise. Using C3H/HeJ mice, we demonstrate that toll-like receptor-4 (TLR-4) plays a role in lipopolysaccharide-induced preterm birth but not in inflammation-induced fetal death. Immunohistochemistry studies demonstrate the presence of the platelet-activating factor receptor in both endometrial glands and smooth muscle in uterine tissues. Molecular studies demonstrate the differential expression of platelet-activating factor receptor and TLR-4 in uterine and cervical tissue throughout gestation. Quantitative polymerase chain reaction revealed an up-regulation of TLR-4 in the fundal region of the uterus in response to intrauterine inflammation. The use of this model will increase our understanding of the significant clinical problem of inflammation-induced preterm birth and will elucidate signal transduction pathways involved in an inflammatory state.
Subject(s)
Disease Models, Animal , Inflammation/complications , Membrane Glycoproteins/metabolism , Obstetric Labor, Premature/metabolism , Platelet Activating Factor/metabolism , Receptors, Cell Surface/metabolism , Animals , Blotting, Western , Female , Immunohistochemistry , Lipopolysaccharides/toxicity , Mice , Obstetric Labor, Premature/chemically induced , Obstetric Labor, Premature/pathology , Platelet Activating Factor/pharmacology , Platelet Membrane Glycoproteins/metabolism , Polymerase Chain Reaction , Pregnancy , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/physiology , Toll-Like Receptor 4 , Toll-Like Receptors , Uterus/drug effects , Uterus/metabolism , Uterus/pathologyABSTRACT
OBJECTIVE: To sequence and characterize the expression of the prothrombinase Fgl-2 in the Sprague-Dawley rat. METHODS: Reverse-transcriptase polymerase chain reaction was performed on RNA from spontaneously cycling adult pregnant Sprague-Dawley rats by using specific Fgl-2 primers. The resulting amplicon was also used to screen a rat spleen bacteriophage library and to probe a Northern blot of various tissues. The rat Fgl-2 amino acid sequence was compared with the known sequences in mouse and human. RESULTS: Fgl-2-specific amplicon bands were observed in the rat brain, kidney, liver, ovary, spleen, and gestational day 22 and postpartum uterus. The rat Fgl-2 cDNA and amino acid sequence were found to be homologous with those of human (86% and 74%, respectively) and mouse (91% and 87%, respectively). Northern blotting demonstrated two different-sized transcripts (1.3 and 3.4 kb), and expression was observed in the cervix, heart, liver, ovary, and nongestational and gestational day 22 myometrium. CONCLUSION: Thrombin is classically generated from the cleavage of the proenzyme prothrombin by activated factors V and X. In tissues thrombin appears to be generated by a novel prothrombinase Fgl-2 (fibrinogen-like protein) whose activity is stimulated by proinflammatory mediators. Fgl-2 provides the mechanistic coupling between proinflammatory cytokines and the generation of active thrombin independent of the coagulation cascade. Our studies confirmed the expression of Fgl-2 mRNA in several rat tissues, including the pregnant uterus, where it could play a key role in the initiation of parturition especially in response to local or systemic infection.
