Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Functional genomics in perinatal asphyxia and fetal asphyctic preconditioning in the brain

ABSTRACT: Fetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore, we investigated whole genome differential expression in the preconditioned rat brain. FA preconditioning was induced on embryonic day 17 (E17) by reversibly clamping the uterine circulation. Perinatal asphyxia (PA) was induced while pups were being born by caesarean section; the uterine horns, including pups, were placed in a water bath for 19 minutes. FAPA pups underwent both procedures. Control (C) pups did not undergo FA or PA procedures, but were born by caesarean section. Pups were sacrificed at 3 time-points: 96 hours after FA (E21), 6 hours after birth/PA (P0), and 96 hours after birth/PA (P4).

ORGANISM(S): Rattus norvegicus

SUBMITTER: Wouter Van Delm

PROVIDER: E-GEOD-42676 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.

Cox-Limpens Kimberly E M KE Vles Johan S H JS LA van den Hove Daniel D Zimmermann Luc J I LJ Gavilanes Antonio W D AW

BMC neuroscience 20140529

<h4>Background</h4>Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates.Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditi ...[more]

PMID: 24885038

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Project description:Aside from the perinatal complications associated with low birth weight, individuals born with intra-uterine growth restriction suffer from chronic diseases late in life that ultimately lead to a shortened lifespan. These late life metabolic sequelae of low birth weight include obesity and metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Animal models employing perinatal calorie restriction recapitulate the observations made in humans. Interestingly, if continued calorie restriction is employed post-natally the late life sequelae of intra-uterine growth restriction are ameliorated. These observations linking both fetal and early post natal growth to later health is now termed the developmental origins of health and disease. To further our understanding of the mechanism of how early growth affects late life health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression in a rat model of maternal semi-nutrient restriction. In these experiments we have limited maternal calorie intake to 50% of normal so as to create 3 groups of animals: Control (Con) male offspring born to mothers who were fed normally throughout gestation and lactation; intra-uterine calorie restricted male offspring (IUCR) born to mothers who had 50% restriction of calories from e11 to e21; and combined intra-uterine and post-natal calorie restriction (IPCR) male offspring who were born to mothers who received calorie restriction during both fetal growth (e11 to e21) and post-natally (p1-p21). Livers were collected at p21(day 21 of life) for Con and IPCR groups (IUCR withheld owing to ‘catch up” growth), and at p450 (day 450 of life) for Con, IUCR, and IPCR. The profiling data reveals clear alteration of circadian cycling at P21, and subtle changes for circadian gene expression at p450. In addition, a clear transcriptional response is found during active calorie restriction at p21 but an absence of a transcriptional response late in life at p450. Transcritional studies have been performed using Affymetrix Rat Gene 1.0 arrays for the following treatment groups, with each group run in triplicate (each replicate from separate littermates): Day 21 Control, Day 21 IPCR, Day 450 Con, Day 450 IUCR, Day 450 IPCR

Project description:We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, pro-angiogenic, anti-fibrotic and proliferative effects on target cells. hAFS can be also isolated from III trimester clinical waste samples during C-section scheduled procedures (perinatal hAFS), thus offering an easily accessible alternative source. Nonetheless, little is known about their paracrine profile. Here we provide a detailed characterization of the hAFS total secretome (i.e. whole of the soluble paracrine factors released by the cells in their conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it as from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. Their secretome formulations were analyzed in terms of protein and chemokine/cytokine content, with the EV cargo further investigated by RNA sequencing. While the appearance of fetal and perinatal hAFS, along with their corresponding secretome formulations was overlapping, the profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. While both cell sources provided paracrine formulations enriched with neurotrophic, immunomodulatory and endothelial stimulating factors, the more immature fetal hAFS secretome was defined by a more pronounced pro-angiogenic, pro-resolving and anti-aging profile over the perinatal one, while the corresponfing EV…. Moreover, small RNA profiling showed a relevant enrichment of microRNA in both the fetal and perinatal hAFS-EV cargo, with a steadily expressed pro-resolving miRNA core as reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario.

Dataset Information

Functional genomics in perinatal asphyxia and fetal asphyctic preconditioning in the brain

Publications

Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.

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