Project description:Macrophages and neutrophils were sorted from the decidua and uterus of Nlrp3+/+ and Nlrp3-/- mice injected with lipopolysaccharide (LPS) or PBS and analyzed using pair-end RNA-sequencing (RNA-seq) to evaluate the effect of Nlrp3 deficiency on the transcriptomes of these innate immune cells in preterm birth.
Project description:Preterm birth is often predisposed by chorioamnionitis (CA) and CA affects the fetal gut and lungs via intra-amniotic (IA) inflammation, thus accentuating the proinflammatory effects of preterm birth. It is not known if IA inflammation also affects other perfusion-sensitive organs (e.g., kidneys) before and after preterm birth. Using preterm pigs as model for preterm infants, we hypothesized that CA induces fetal and neonatal renal dysfunctions that can intially be detected via plasma proteome, partly explaining the frequent renal dysfunction in preterm infants. Fetal pigs (88% gestation) were given an IA dose of lipopolysaccharide (LPS, 1 mg/kg, n=28), delivered preterm by cesarean section three days later, and compared with controls (CON, n=26) at birth and postnatal day five. Plasma proteome and protein markers of inflammatory pathways were evaluated.
Project description:Using RNA-sequencing (RNA-Seq and miRNA-Seq), we analyzed paired villous trophoblast and decidual basalis transcriptomes of 15 women pregnant with singleton gestations grouped as follows: (1) spontaneous preterm birth (PTB) in the setting of amniocentesis-proven intra-amniotic infection (IAI) and histological chorioamnionits (n=5; GA median [range]: 26 [25-31] weeks); (2) spontaneous idiopathic preterm birth (iPTB, n=5, GA: 32 [30-33] weeks); and (3) term normal pregnancy, that delivered a heathy infant by cesarean section in the absence of labor (n=5; GA: 39 [38-39] weeks).
Project description:Using RNA-sequencing (RNA-Seq and miRNA-Seq), we analyzed paired villous trophoblast and decidual basalis transcriptomes of 15 women pregnant with singleton gestations grouped as follows: (1) spontaneous preterm birth (PTB) in the setting of amniocentesis-proven intra-amniotic infection (IAI) and histological chorioamnionits (n=5; GA median [range]: 26 [25-31] weeks); (2) spontaneous idiopathic preterm birth (iPTB, n=5, GA: 32 [30-33] weeks); and (3) term normal pregnancy, that delivered a heathy infant by cesarean section in the absence of labor (n=5; GA: 39 [38-39] weeks).
Project description:Using RNA-sequencing (RNA-Seq and miRNA-Seq), we analyzed paired villous trophoblast and decidual basalis transcriptomes of 15 women pregnant with singleton gestations grouped as follows: (1) spontaneous preterm birth (PTB) in the setting of amniocentesis-proven intra-amniotic infection (IAI) and histological chorioamnionits (n=5; GA median [range]: 26 [25-31] weeks); (2) spontaneous idiopathic preterm birth (iPTB, n=5, GA: 32 [30-33] weeks); and (3) term normal pregnancy, that delivered a heathy infant by cesarean section in the absence of labor (n=5; GA: 39 [38-39] weeks). The primary goal of this study was to identify differentially expressed transcripts and illuminate molecular mechanisms distinguishing IAI-associated PTBs from spontaneous PTBs in the absence of IAI. We further compared iPTB specimens to term specimens to determine genes differentially regulated with advancing gestational age and following spontaneous PTB without IAI. Finally, we determined transcripts selectively expressed in either the villous trophoblast or decidua basalis in each clinical context. Raw data for this series are not available because consent forms do not allow for public access to raw data.
Project description:Using RNA-sequencing (RNA-Seq and miRNA-Seq), we analyzed paired villous trophoblast and decidual basalis transcriptomes of 15 women pregnant with singleton gestations grouped as follows: (1) spontaneous preterm birth (PTB) in the setting of amniocentesis-proven intra-amniotic infection (IAI) and histological chorioamnionits (n=5; GA median [range]: 26 [25-31] weeks); (2) spontaneous idiopathic preterm birth (iPTB, n=5, GA: 32 [30-33] weeks); and (3) term normal pregnancy, that delivered a heathy infant by cesarean section in the absence of labor (n=5; GA: 39 [38-39] weeks). The primary goal of this study was to identify differentially expressed transcripts and illuminate molecular mechanisms distinguishing IAI-associated PTBs from spontaneous PTBs in the absence of IAI. We further compared iPTB specimens to term specimens to determine genes differentially regulated with advancing gestational age and following spontaneous PTB without IAI. Finally, we determined transcripts selectively expressed in either the villous trophoblast or decidua basalis in each clinical context. Raw data for this study are not available because consent forms do not allow for public access to raw data.
Project description:Decidual and uterine macrophages as well as neutrophils from Nlrp3+/+ and Nlrp3-/- mice injected with S100B or PBS were sorted and analyzed using pair-end BGI RNA sequencing (RNA-seq) to evaluate the effect of Nlrp3 deficiency on the transcriptome of these innate immune cells in preterm birth.
Project description:Uterine stretch is thought to induce preterm labor in women with twin and higher order pregnancies, but the pathophysiology remains unclear. We investigated the pathogenesis of stretch-induced preterm birth for the first time in a pregnant nonhuman primate model. Eleven chronically catheterized pregnant monkeys (Macaca nemestrina) at 118-125 days gestation (term=172 days) received either: 1) inflation of intra-amniotic balloons (N=6) or 2) saline inoculation (N=5). Cesarean section and fetal necropsy was performed due to preterm labor or to collect tissues, except in one case where the animal delivered spontaneously, reducing samples for microarray analysis to ten (five stretch and five control animals). Amniotic fluid and maternal plasma were analyzed for multiple cytokines and prostaglandins using Luminex, enzyme-linked immunosorbent assay and Analysis of Covariance. Ribonucleic acid was extracted from the myometrium in the lower uterus at Cesarean section and analyzed by microarray and quantitative reverse transcriptase polymerase chain reaction.
Project description:Preterm birth, defined as birth <37 weeks of gestation, is a leading cause of infant morbidity and mortality. In the United States, approximately 12% of all births are preterm.1 Despite decades of research, there has been little progress in developing effective interventions to prevent preterm birth. In fact, the rate of preterm birth has increased slightly over the last several decades.2 The ultimate goal of the Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) is to identify possible biomarkers that could predict the susceptibility to spontaneous preterm birth (SPTB) as well as to shed light on the molecular mechanisms involved in its etiologies. Understanding those mechanisms will help us predict SPTB and may facilitate the introduction of more effective prevention and treatment strategies.