Placental mitochondrial calcium uniporter modulates offspring susceptibility to obesity in a sex-dependent manner
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE294553 | GEO | 2025/04/15
REPOSITORIES: GEO
Similar Datasets
Project description:To characterise the transcriptome of mouse placental junctional zone cells in Control litters (deletion of the maternally-inherited and silent Igf2 allele, with normal Igf2 levels in whole litters) in UE litters (dams carried offspring with a deletion of the paternally-inherited Igf2 allele in the placental endocrine cells with diminished Igf2 production from the endocrine cells in whole litters), we performed single nucleus RNA sequencing on the placenta Junctional zone 8 Control placentas (offspring sex: 4M:4F) and 8 UE placentas (offspring sex: 4M:4F) in 2 batches each.
2023-04-30 | GSE229514 | GEO
Project description:The placenta serves as the structural interface for nutrient and waste exchange for proper fetal development. Although defects in placental function result in various placental disorders, molecular mechanisms orchestrating placental development and function are poorly understood. Gene targeting studies have shown that Hgf or c-Met KO embryos exhibit growth retardation and markedly smaller size of the placenta, and die by E14.5. Stem/progenitor cells in various tissues express c-Met and they participate in morphogenesis and tissue repair. Thus, we hypothesized that the HGF/c-Met signaling pathway is essential for the emergence, proliferation, and/or differentiation of putative stem/precursor cells of labyrinth trophoblasts at the midgestation stage. To examine the downstream mechanisms of HGF/c-Met signaling pathway that regulate placental labyrinth development, we performed microarray analysis and compared the transcriptional profiles of wild-type and c-Met g-KO placentas. The highly enriched gene ontology categories among the transcripts that were down-regulated in the mutant placentas were related to cell cycle, transcription, and placenta development. Surprisingly, the most highly enriched GO category among the up-regulated genes was immune response. Furthermore, genes classified as “unsaturated fatty acid metabolic process” were also significantly enriched among the up-regulated genes. This expression data suggested that HGF/c-Met signaling pathway positively regulates progression of cell cycle and transcription of placenta specific genes, and negatively regulates inflammatory reaction and fatty acids synthesis in the trophoblasts, thereby coordinating many critical cellular processes in the placenta. Freshly harvested mouse placental trophoblast was enriched for CD9 from wild -type and c-Met KO placenta with 2 independent biological replicates
2013-12-31 | E-GEOD-38342 | biostudies-arrayexpress
Project description:Previously, we have examined the effect of maternal dietary n-3 LCPUFA supplementation during pregnancy to reduce offspring obesity risk. Considering the involvement of the placenta in fetal programming, we here analyzed the sexually dimorphic potential of placental gene expression, its response to the n-3 LCPUFA intervention and their correlation to offspring obesity risk. The placenta is implicated to play a key role in mediating fetal /metabolic programming of the offspring in utero. For human and mouse models, it has been reported that male and female fetuses differentially respond to in utero environmental stimuli. Moreover, sexual dimorphism is also known for placental gene expression, LCPUFA metabolism and adipose tissue distribution. Therefore, we explored whether the maternal n-3 LCPUFA intervention during pregnancy has a sex-specific impact on the term placental transcriptome in a defined subpopulation of the INFAT (impact of nutritional fatty acids during pregnancy and lactation on early human adipose tissue development) study. In addition, we assessed the relationships between sex-specific placental gene expression and sex steroids levels, and expression changes of specific genes and offspring obesity risk. Overall, human term placentas show sexually dimorphic gene expression and respond sex-specifically to dietary maternal n-3 LCPUFA intervention during pregnancy with more pronounced effects on gene expression and estradiol-17β/testosterone ratio in female than male placentas.
2014-10-30 | GSE53291 | GEO
Project description:Background: Maternal iron deficiency (ID) is associated with poor pregnancy and fetal outcomes. The effect is thought to be mediated by the placenta but there is no comprehensive assessment of placental response to maternal ID. Additionally, whether the influence of maternal ID on the placenta differs by fetal sex is unknown. Objectives: Our primary aim was to identify gene and protein signatures of ID mouse placentas at mid-gestation. A secondary objective was to profile the expression of iron genes in mouse placentas across gestation. Methods: We used a real-time PCR based array to determine the mRNA expression of all known iron genes in mouse placentas at embryonic day (E) 12.5, E14.5, E16.5, and E19.5 (n=3 placentas/time point). To determine the effect of maternal ID, we performed RNA sequencing and proteomics in male and female placentas from ID and iron adequate mice at E12.5 (n=8 dams/diet). Results: In female placentas, six genes including transferrin receptor (Tfrc) and solute carrier family 11 member 2 were significantly changed by maternal ID. An additional 154 genes were altered in male ID placentas. Proteomic analysis quantified 7662 proteins in the placenta. Proteins translated from iron responsive element (IRE) containing mRNAs were altered in abundance; ferritin and ferroportin 1 decreased while TFRC increased in ID placenta. Less than 4% of the significantly altered genes in ID placentas occurred both at the transcriptional and translational levels. Conclusions: Our data demonstrate that the impact of maternal ID on placental gene expression in mice is limited in scope and magnitude at mid-gestation. We provide strong evidence for IRE-based transcriptional and translational coordination of iron gene expression in the mouse placenta. Finally, we discover sexually dimorphic effects of maternal ID on placental gene expression, with more genes and pathways altered in male compared with female mouse placentas.
2021-03-12 | PXD023454 | Pride
Project description:The term placenta is a highly vascularized tissue and is usually discarded upon birth. Our objective was to isolate clinically relevant quantities of fetal endothelial colony-forming cells (ECFCs) from human term placenta and to compare them to the well-established donor-matched umbilical cord blood (UCB)-derived ECFCs. A sorting strategy was devised to enrich for CD45-CD34+CD31Lo cells prior to primary plating to obtain pure placental ECFCs (PL-ECFCs) upon culture. UCB-ECFCs were derived using a well-described assay. PL-ECFCs were fetal in origin and expressed the same cell surface markers as UCB-ECFCs. Most importantly, a single term placenta could yield as many ECFCs as 27 UCB donors. PL-ECFCs and UCB-ECFCs had similar in vitro and in vivo vessel forming capacities and restored mouse hind limb ischemia in similar proportions. Gene expression profiles were only minimally divergent between PL-ECFCs and UCB-ECFCs, probably reflecting a vascular source versus a circulating source. Finally, PL-ECFCs and UCB-ECFCs displayed similar hierarchies between high and low proliferative colonies. We report a robust strategy to isolate ECFCs from human term placentas based on their cell surface expression. This yielded much larger quantities of ECFCs than UCB, but the cells were comparable in immunophenotype, gene expression, and in vivo functional ability. We conclude that PL-ECFCs have significant bio-banking and clinical translatability potential. Data has been integrated into the Stemformatics web resource http://www.stemformatics.org/datasets/view/6306
2015-03-02 | E-MTAB-3277 | biostudies-arrayexpress
Project description:Introduction: Maternal immune activation (MIA), characterized by increased circulating inflammatory mediators during pregnancy, is associated with adverse pregnancy outcomes and neurodevelopmental deficits in offspring. These health outcomes often manifest differently depending on fetal-placental sex. A well-established model of MIA involves administration of a viral mimetic, polyinosinic:polycytidilic acid (PolyI:C), to pregnant rodents. Placental responses to PolyI:C contribute to the detrimental effects of MIA on offspring, but these responses have not yet been well characterized. In the present study, we profiled acute gene expression changes in male and female placentas following PolyI:C administration to pregnant rats. Methods: Pregnant rats received 4 mg/kg PolyI:C or saline intravenously on gestational day 18.5, and tissues were harvested 4-5 hours later. Gene expression profiling on placental tissue was performed. Enzyme immunoassays and immunohistochemistry were conducted to determine levels of select proteins in maternal blood and placental tissue, respectively. Results: Maternal PolyI:C exposure caused a robust increase in levels of inflammatory markers in maternal blood and placental tissue. There were more genes differentially expressed in female placentas after PolyI:C exposure (765) than male placentas (221), including reduced expression of genes associated with maternal-fetal communication. Placentas also had increased expression of genes linked with vascular dysfunction after PolyI:C-induced MIA. Discussion: PolyI:C elicited a powerful inflammatory response in the placenta along with vascular dysfunction, likely contributing to the adverse pregnancy outcomes triggered by MIA. Female placentas responded to PolyI:C more vigorously than male placentas, which could underlie the differential outcomes of MIA depending on sex.
2025-03-21 | GSE272437 | GEO
Project description:The placenta serves as the structural interface for nutrient and waste exchange for proper fetal development. Although defects in placental function result in various placental disorders, molecular mechanisms orchestrating placental development and function are poorly understood. Gene targeting studies have shown that Hgf or c-Met KO embryos exhibit growth retardation and markedly smaller size of the placenta, and die by E14.5. Stem/progenitor cells in various tissues express c-Met and they participate in morphogenesis and tissue repair. Thus, we hypothesized that the HGF/c-Met signaling pathway is essential for the emergence, proliferation, and/or differentiation of putative stem/precursor cells of labyrinth trophoblasts at the midgestation stage. To examine the downstream mechanisms of HGF/c-Met signaling pathway that regulate placental labyrinth development, we performed microarray analysis and compared the transcriptional profiles of wild-type and c-Met g-KO placentas. The highly enriched gene ontology categories among the transcripts that were down-regulated in the mutant placentas were related to cell cycle, transcription, and placenta development. Surprisingly, the most highly enriched GO category among the up-regulated genes was immune response. Furthermore, genes classified as “unsaturated fatty acid metabolic process” were also significantly enriched among the up-regulated genes. This expression data suggested that HGF/c-Met signaling pathway positively regulates progression of cell cycle and transcription of placenta specific genes, and negatively regulates inflammatory reaction and fatty acids synthesis in the trophoblasts, thereby coordinating many critical cellular processes in the placenta.
2013-12-31 | GSE38342 | GEO
Project description:The placenta acts as an interface between the mother and fetus, regulating nutrient transport and secreting hormones which impact maternal metabolism. Complications during pregnancy, such as placental endocrine malfunction, programme offspring to develop metabolic disease during adulthood, in part via changes in gene expression in critical metabolic organs, such as the liver, during fetal development. Placental endocrine malfunction was induced via the misexpression of two imprinted genes (Igf2 and H19) exclusively in the endocrine zone of the mouse placenta, to study the consequences this has on fetal hepatic gene expression.
2023-11-30 | E-MTAB-11457 | biostudies-arrayexpress
Project description:Advanced paternal age has been shown to be a significant risk factor for neurodevelopmental psychiatric disorders, particularly autism. We have recently shown that mice conceived by old fathers display behavioral abnormalities which resemble key diagnostic symptoms of human autism. De novo mutations and epigenetic alterations increase in the male germ line during ageing and are thought to mediate the effect of paternal age on occurrence of diseases occurrence. Because the placenta carry a predominantly fetal genetic background, age-related mutagenesis and epigenetic errors might negatively influence placental physiology and in turn perturb fetal brain development. Here, we examined the impact of paternal age on placental mRNA transcriptome. This work was supported by Programme FP7-KBBE-2012.1.3-04, GA no. 312097 Acronym: FECUND, to GEP; MIUR/CNR, Programme FIRB. GA n. B81J12002520001 Acronym: GenHome, to PL. This study was also partially financed by the IGAB PAS project (S.III.1.3), Polish Scientific Committee Grant 2011/03/N/NZ29/05222, Polish Ministry of Science and Higher Education Grants N N519 657940 and N N311 604938. We compared gene expression patterns of mouse placentas harvested from either advanced paternal age model (APA) of autism or control animals. We included 2 comparisons: 1) placenta of female APA vs placenta of female control; 2) placenta of male APA vs placenta of male control. Each comparison was composed of 3 biological replicates. To minimize family bias, poolings contained at most one placenta per sex from each dam to a minimum of one and a maximum of three placentas per group/sex.
2015-07-25 | E-GEOD-71322 | biostudies-arrayexpress
Project description:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
2021-12-13 | GSE190639 | GEO