Project description:Placental insufficiency is implicated in the intrauterine infection-associated spontaneous preterm birth. Using a mouse model of LPS-induced intrauterine inflammation that leads to preterm delivery, RNA-seq study was performed in the placenta at gestational day 17 to assess the transcriptome changes.
Project description:The study objective was to determine differentially expressed mRNA transcripts in pancreatic islets from fetal sheep with placental insufficiency-induced intrauterine growth restricted.
Project description:The tubal ectopic pregnancy (TEP) is a severe pregnancy complication accounted for 10-15% pregnancy-related deaths owing to the implantation and growth of embryos in fallopian tubes. Placental villi from TEP exhibit significant difference compared with that from intrauterine pregnancy (IP) in total volumes, trophoblast differentiation and intravillous vascularization. To investigate the difference in expression profiles of placental villi from IP and TEP, placental villi were collected from each phenotype, separated from maternal tissues and analyzed by high-throughput sequencing.
Project description:From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the spag7 gene linked to metabolic dysfunction in mice. Here we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a “thrifty phenotype” is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.
Project description:Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributor of perinatal morbility and mortality, these pregnancy disorders associated with placental ischemia and share many similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lnRNAs from pregnant women from four study groups; PE, IUGR, PE-IUGR and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at the moment of delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP (n=461; 314 mRNAs: 252 up-regulated and 62 down-regulated) and 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP (n=39), including 9 lncRNAs with a high correlation degree (P <0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of preeclampsia and Intrauterine Growth Restriction
Project description:The study objective was to determine differentially expressed mRNA transcripts in skeletal muscle from fetal sheep and 30 day old lambs to determine persistent gene changes following placental insufficiency-induced intrauterine growth restriction.
Project description:In this study, we profiled the placental proteome of IUGR twins and normal cotwins from 6 monochorionic twin pairs with selective intrauterine growth restriction (sIUGR).
Project description:Intrauterine hyperglycemia has been linked to an elevated risk of diabetes in next and further generations. Existing reports about transmission effects of intrauterine hyperglycemia have included both intrauterine and postnatal metabolic exposure factors, the impact of intrauterine hyperglycemia per se has not been separately assessed. To investigate effect of intrauterine hyperglycemia exposure per se on further generations, we selected non-phenotypic F1-GDM and F2-GDM male mice to examin metabolic changes in next generation and performed a methylome on day 13.5 primordial germ cells (PGCs) of F1-GDM male fetus to explore its underlying mechanism. We found that intrauterine hyperglycemia exposure per se resulted in obesity, insulin resistance and/or glucose intolerance in F2 male mice, and no changes in F3 male mice. Methylome of day 13.5 PGCs of F1-GDM male fetus revealed differently methylation genes enriched in obesity and diabetic pathogenesis. Methylation validation of targeted gene Fyn showed consistent hypo-methylation status in F1 PGCs, F1 fetal testis, sperm of F1/N-GDM mice, and somatic cells of F2-GDM male mice. While fetal testis of F2-GDM mice showed no alteration in Fyn methylation. Our data indicates that intrauterine hyperglycemia exposure per se contributes to metabolic changes in F2 but not F3 generation, by altering methylation erasure in PGCs of F1 generation.
Project description:The tubal ectopic pregnancy (TEP) is a severe pregnancy complication accounted for 10-15% pregnancy-related deaths owing to the implantation and growth of embryos in fallopian tubes. Placental villi from TEP exhibit significant difference compared with that from intrauterine pregnancy (IP) in total volumes, trophoblast differentiation and intravillous vascularization. To investigate the difference in expression profiles of placental villi from IP and TEP, placental villi were collected from each phenotype, separated from maternal tissues and analyzed by high-throughput sequencing. generated a mouse model in which p53 is activated in neural crest cells due to the expression of a mutant p53 protein (p53-25,26) that can bind to and stabilize wild-type p53. Here, we performed gene expression profiling on neural crest cells isolated from these embryos, to identify the transcriptional response to p53 activation during embryogenesis.
