Mus musculus strain:ICR
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB17028 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:HFHC_F_C NASH mouse model transcriptome
| PRJNA825166 | ENA
Project description:Introduction: Low birthweight is a risk factor for chronic kidney disease (CKD), in part due to an associated low nephron number, but the mechanisms leading to increased risk are not well understood. Low birthweight and growth restriction can be modeled in mice using gestational low protein (LP). Using this model, here we sought to 1) identify a potential window for therapeutic intervention to prevent future CKD in LP animals, 2) understand the transcriptional impact of LP on adult kidneys, and 3) clarify the mechanistic connection between low nephron endowment and predisposition to disease in LP animals. We hypothesized that gestational LP-induced growth restriction would lead to shorter nephrogenesis and altered gene expression in adulthood. Methods: At the initiation of pregnancy, CD-1 dams received a normal protein (NP, 18%) or LP (8%) diet. Offspring were euthanized on postnatal days (PN) 2-7 (n=2-7/day). Kidneys were stained with Periodic acid–Schiff (PAS). Immunofluorescence was used to assess SIX2 (progenitor cells), JAG1 (nascent nephron patterning), and LEF1 (Wnt signaling). At 6 weeks, mice underwent transdermal glomerular filtration rate (GFR) measurement. Ex vivo kidneys underwent histologic evaluation, bulk RNA sequencing, and cationic ferritin- enhanced MRI to quantify glomerular number (Nglom). Results: LP mice had protracted nephrogenesis extending to PN5-6, compared to NP mice that had completed nephrogenesis by PN3-5. Adult LP mice had fewer glomeruli, and LP males had lower GFR and more ATG compared to NP males. LP mice did not have evidence of glomerular hypertrophy. In LP males, the following genes were downregulated: Gfr1, Pax8, Fgf10, Dvl1, and Aldh1a1. Foxd1, Hif1an, Egln3, and Fzd7 were upregulated in the LP males. LP females exhibited upregulation of Etv5 and Osr2 and downregulation of Gata3, Mgp, and Trpv6 with no overlap of dysregulated genes between the sexes. Conclusions: LP offspring exhibit prolonged nephrogenesis and a reduced nephron endowment in adulthood. In males, this is characterized by a suppressed retinoic acid–GDNF–Wnt axis, while both sexes show persistent dysregulation of developmental genes. Together, these findings identify the late gestational and early postnatal periods as critical therapeutic windows. Targeting these molecular pathways during active nephrogenesis may offer a strategy to mitigate the programmed risk of CKD in growth-restricted offspring.
2026-03-03 | GSE320330 | GEO
Project description:Taurine is known to be important for fetal well being and to be able to prevent effects of a low birthweight phenotype when supplemented to pregnant dams. We hypothesized that gestational taurine supplementation would affect gene expression level in 4w offspring liver and skeletal muscle.
2010-12-01 | GSE20577 | GEO
Project description:<p>The gut microbiota operates at the interface of host-environment interactions to influence human homeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore elicit physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline - and consequently on the F1 offspring it gives rise to - is unexplored. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory ‘gut-germline axis’ in males, which is sensitive to environmental exposures and programs offspring fitness through impacting placental function.</p>
2024-02-12 | MTBLS1629 | MetaboLights
Project description:Maternal caloric restriction during the last week of gestation resulted in low birth weight (LBW) and increased risk of LBW-associated metabolic diseases in adult life. The metabolic phenotypes transmitted to F2 generation by paternal manner without additional altered nutrition. To investigate the mechanism of this intergenerational inheritance, two Cohorts were exposed to different magnitudes of undernutrition both in utero during the last week of gestation and/or postnatal until weaning. We performed MeDIP-seq on the genomic DNA from sperm collected from these mice.
2024-08-25 | E-MTAB-9567 | biostudies-arrayexpress
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in expression of genes regulating fetal growth and metabolism. In a complementary study we investigated DNA methylation in the same samples.
2019-01-31 | E-MTAB-6418 | biostudies-arrayexpress
Project description:Taurine is known to be important for fetal well being and to be able to prevent effects of a low birthweight phenotype when supplemented to pregnant dams. We hypothesized that gestational taurine supplementation would affect gene expression level in 4w offspring liver and skeletal muscle. Pregnant mouse dams were subjected to different diet schemes from day 1 of pregnancy until birth. Pups were killed at 4 weeks of age and liver and quadriceps skeletal muscle taken out and frozen at -80C until analysis. Diet schemes: Normal Protein (20% casein; NP), Normal Protein + taurine (1% taurine supplementation in water ad libitum; NP+tau). The liver and muscle samples were normalized separately.
2010-12-01 | E-GEOD-20577 | biostudies-arrayexpress
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in DNA methylation of genes regulating fetal growth and metabolism. In a related study we investigated the gene expression in the same samples.
2018-11-01 | E-MTAB-6421 | biostudies-arrayexpress
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
2014-12-04 | E-GEOD-61417 | biostudies-arrayexpress
Project description:Maternal caloric restriction during the last week of gestation resulted in a low birth weight (LBW) and increased risk of LBW-associated metabolic diseases in adult life. The metabolic phenotypes transmitted to F2 generation by paternal manner without additional altered nutrition. To investigate the mechanism of this intergenerational inheritance, two Cohorts were exposed to different magnitudes of unternourition both in utero during the last week of gestation and/or post nataly until weaning. We performed small RNA-seq on non-coding RNA from sperm collected from these mice. Small RNA libraries were size-selected to be between 132 to 200 bp (including adapter) after library amplification.
2024-08-25 | E-MTAB-9565 | biostudies-arrayexpress