Alternative Splicing: a prominent mechanism in the Human pathological placenta
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ABSTRACT: Placentas from preeclamptic pregnancies, pregnancies with Intra-uterine Growth restriction, control pregnancies from two Cohorts (Paris, Cochin Hospital and Angers Hospital) were hybridized to ClariomD microarrays and analyzed at the exon level to identify and evaluate putative anomalies in alternative splicing in human placentas.
Project description:Total RNAs extracted from placental villi collected from women with (vaginal delivery) or without labor (cesarean section) at term (37-42 weeks of gestation) were hybridized to ClariomD microarrays and analyzed at the gene level to evaluate differential expression genes postlabor
Project description:STOX1 overexpressing placentas generate preeclampsia-like symptoms in pregnant mice. These symptoms are reverted by aspirin. The experiment aims at analyzing placental expression in Transgenic/non transgenic with and withou aspirin, in the placentas at 16,5 days post-coïtum. There are two strains of transgenic mice that express the transgene at different levels: STOX42 about 15 fold that of STOX13. STOX13 expressed the human STOX1 roughly at the level of the mouse endogeneous Stox1 in the placenta.
Project description:Two pools of three placentas from transgenic mice of the TG13 strain and WT mice were hybridized on Nimblegen Arrays. TG13 mice overexpress the gene STOX1 and have the symptoms of severe preeclamsia. Total RNA was used
Project description:Aspirin is currently the only drug used in preeclampsia, a major hypertensive disorder of pregnancy. The counselled doses are low (75-150 mg/day), and the actual effects of aspirin are not well understood, especially in the target organ, the placenta.This is the aim of the present study.
Project description:R3 IRCS have a 6 Mb fragment of mouse chromosome 1 originating from Mus spretus; they display a increase rate of embryonic mortality Eight samples corresponding to two pools of three placentas, three uterus for the two strains (B6 and R3 IRCS) were hybridized on a four-quadrant Nimblegen expression array (two tissues x two types of mice x 2 duplicates)
Project description:Trophoblast fusion is a central step in placental physiology. This mechanisms can be studied in the BeWO cell model that fuse following forskolin treatment that activates the c-AMP cascade.
Project description:Long-term consequences of preeclampsia were studied by high-throughput approaches (Transcriptomics, Luminex cytokine profile) in mice 8 months after the disease in the heart, in the endothelial cells and in the plasma. In the heart we found a persisting ventricular hypertrophy with an altered histology and an abnormal ultrasound Doppler profile under effort simulation by dobutamine injection. The transcriptomic profile of the endothelium revealed a deregulation for 1149 genes (327 down-regulated and 822 up-regulated, with a threshold of 1.5, p<0.05). The up-regulated genes could be grouped consistently in gene pathways and gene ontology terms mainly focused on Inflammation and Stress sensu lato. A cytokine profile of the mouse serum was carried out. Using a combination of 8 cytokines (Cxcl13, Cxcl16, Cxcl11, Il-16, Il-10, Il-2, Il-4 and Ccl1) in a Discriminant Analysis, we were able to separate unambiguously the mice having had a preeclamptic pregnancy from the controls. Seven out of eight of these cytokines (with the exception of Il-16) varied in the same direction in the endothelium and in the plasma. In sum, our study shows that preeclampsia alone is able to trigger considerable long-term consequences, and suggests that specific cytokines could help to improve the follow-up of patients long after a preeclamptic pregnancy.
Project description:STOX1A overexpression in mice placenta triggers a preeclamptic phenotype in the mothers, with hypertension, proteinuria and kidney alterations (Doridot et al, Hypertension, 2013), this being connected with NO depletion and increase of nutrosative stress (Doridot et al, Antiox Redox Signal, 2014). Tetrahydrobiopterin (BH4) is a cofactor essential for NO production. We treated preeclamptic mice with this drug, and analyzed placental gene expression in four groups (Control mice, Control mice with BH4, Preeclamptic mice and preeclamptic mice with BH4).
Project description:This experiment is one of a series of experiments on interspecific recombinant congenic strain (IRCS) mice that aimed to identify novel genes involved in male or female hyporfertility by comparing characteristics of the sperm, number of offspring, quality of implantation etc. in C57B6/J and IRCS mice. <br>The goal of this experiment was to understand the basis of female hypofertility/embryonic resorption in a mouse model of congenic strains. The IRCS strain used in this experiment is the 66H Ch13 mouse. This strain was derived by introgression of a ~6 Mb fragment of mus spretus origin inside the genome of Mus musculus (C57B6/J) (L'hôte et al, Bioessays, 2010. PMID:20091755 ) Previous ultrasonographic analysis of this line revealed an increased rate of embryonic resorption compared to the C57B6/J parent (Laissue et al, Int. J . Dev. Biol, 2009 PMID: 19488966 ). <br>In this experiment we measured gene expression in the tissues that are relevant for implantation and early development, i.e. the uterus and the placenta, in C57B6/J and 66H Chr13 mice at 12 days post-coïtus with C57B6/J males. Pools of RNA from four mice per sample were obtained and analysed using a Nimblegen mouse expression array.
Project description:Three variants of STOX1 (Y153H, T188N, and R364X) were associated to diseases of pregnancy (preeclampsia and HELLP syndrome). Here we analyze the expression profile of these mutations (6 independent clones) starting from two independent Knocked-Out cell lines (KO5 and KO21).