The maternal microbiome promotes placental development in mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198947 | GEO | 2022/03/21
REPOSITORIES: GEO
Similar Datasets
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:“Dysbiosis" of the maternal gut microbiome, in response to environmental challenges such as infection, altered diet and stress during pregnancy, has been increasingly associated with abnormalities in offspring brain function and behavior. However, whether the maternal gut microbiome regulates neurodevelopment in the absence of environmental challenge remains unclear. In addition, whether the maternal microbiome exerts such influences during critical periods of embryonic brain development is poorly understood. Here we investigate how depletion, and selective reconstitution, of the maternal gut microbiome influences fetal neurodevelopment in mice. Embryos from antibiotic-treated and germ-free dams exhibit widespread transcriptomic alterations in the fetal brain relative to conventionally-colonized controls, with reduced expression of several genes involved in axonogenesis. In addition, embryos from microbiome-depleted mothers exhibit deficient thalamocortical axons and impaired thalamic axon outgrowth in response to cell-extrinsic guidance cues and growth factors. Consistent with the importance of fetal thalamocortical axonogenesis for shaping neural circuits for sensory processing, restricted depletion of the maternal microbiome from pre-conception through mid-gestation yields offspring that exhibit tactile hyposensitivity in select sensorimotor behavioral tasks. Gnotobiotic colonization of antibiotic-treated dams with a limited consortium of spore-forming bacteria indigenous to the gut microbiome prevents abnormalities in fetal brain gene expression, fetal thalamocortical axonogenesis and adult tactile sensory behavior associated with maternal microbiome depletion. Metabolomic profiling reveals that the maternal microbiota regulates levels of numerous small molecules in the maternal serum as well as the brains of fetal offspring. Select microbiota-dependent metabolites – trimethylamine N-oxide, 5-aminovalerate, imidazole propionate, and hippurate – sufficiently promote axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with the metabolites during early gestation abrogates deficiencies in fetal thalamocortical axons and prevents abnormalities in tactile sensory behavior in offspring from microbiome-depleted dams. Altogether, these findings reveal that the maternal gut microbiome promotes fetal thalamocortical axonogenesis and select tactile sensory behaviors in mice, likely by signaling of microbially modulated metabolites to neurons in the developing brain.
2020-04-17 | GSE147183 | GEO
Project description:The maternal microbiome promotes placental development in mice
| PRJNA817556 | ENA
Project description:The mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming females for parturition, lactation and motherhood. Despite the importance of this connection, the effects of altered placental signaling on the maternal brain are understudied. Here, we show that placental dysfunction alters gene expression in the maternal brain, with the potential to affect maternal behavior. Using a cross between the house mouse and the Algerian mouse in which hybrid placental development is abnormal, we sequenced late gestation placental and maternal medial preoptic area transcriptomes and quantified differential expression and placenta-maternal brain co-expression between normal and hybrid pregnancies. The expression of Fmn1, Drd3, Caln1 and Ctsr was significantly altered in the brains of females exposed to hybrid placentas. Most strikingly, expression patterns of placenta-specific gene families and Drd3 in the brains of house mouse females carrying hybrid litters matched those of female Algerian mice, the paternal species in the cross. Our results indicate that the paternally-derived placental genome can influence the expression of maternal-fetal communication genes, including placental hormones, suggesting an effect of the offspring's father on the mother’s brain.
2019-12-31 | GSE126469 | GEO
Project description:Noninvasive prenatal diagnosis currently used does not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal whole blood have been explored for noninvasive prenatal detection. However, such efforts cover only chromosomal aneuploidy; fetal methylated DNA biomarkers for detecting single-gene disease remain to be discovered. To address this issue, we systematically screened significantly hypermethylated genes in fetal tissues compared with maternal blood for noninvasive prenatal diagnosis of various inherited diseases. First, Methylated-CpG island recovery assay combined with CpG island array was performed in four maternal peripheral bloods and their corresponding placental tissues. Subsequently, direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out to validate the reliability of methylation microarray analysis. As results, 310 significantly hypermethylated genes in fetal tissues were detected by microarray. Two of five randomly selected hypermethylated genes detected by microarray were confirmed to be hypermethylated in fetal tissue samples by direct bisulfite sequencing. All four randomly selected hypermethylated genes detected by microarray were confirmed to be hypermethylated in five independent amniotic fluid samples and five independent chorionic villus samples from 10 pregnant women by CORBA. In conclusions, We found a lot of hypermethylated genes and methylation sites in fetal tissues, some of which have great potential to be developed into molecular markers for noninvasive prenatal diagnosis of monogenic disorders. Further clinical study is warranted to confirm these findings. Paired experiments, placental tissues vs. maternal peripheral bloods. Biological replicates: 4 placental tissues and 4 correspoding maternal peripheral bloods.
2012-02-22 | E-GEOD-35997 | biostudies-arrayexpress
Project description:Maternal influenza A viral infections in humans are associated with low birth weight, increased risk of pre-term birth, stillbirth and congenital defects. To examine the effect of maternal influenza virus infection on placental and fetal growth, pregnant C57BL/6 mice were inoculated intranasally with influenza A virus A/CA/07/2009 pandemic H1N1 or PBS at E3.5, E7.5 or E12.5, and the placentae and fetuses collecgted and weighed at E18.5. Fetal thymuses were pooled from each litter. Placentae were examined histologically, stained by IHC for CD34 and vascular channels quantified. RNA from E7.5 and E12.5 placentae and E7.5 fetal thymuses was subjected to RNA sequencing and pathway analysis. Placental weights were decreased in litters inoculated with influenza at E3.5 and E7.5. Placentae from E7.5 and E12.5 inoculated litters exhibited decreased labyrinth development and transmembrane protein 150A gene was upregulated in E7.5 placentae. Fetal weights were decreased in litters inoculated at E7.5 and E12.5 compared to controls. RNA sequencing of E7.5 thymuses indicated that 957 genes were downregulated 2-fold including Mal, which is associated with Toll-like receptor signaling and T cell differentiation. There were 28 upregulated genes. It is concluded that maternal influenza A virus infection impairs fetal thymic gene expression as well as restricting placental and fetal growth.
2020-09-11 | GSE157132 | GEO
Project description:Maternal obesity is becoming a major health consideration for successful pregnancy outcomes. There is growing proof that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are so far poorly understood. We set out to analyse term placenta whole transcriptome in obese (n=5) and normoweight women (n=5), using Affymetrix microarray platform compromising of 50,000 probe sets. Our analysis shows that the placental transcriptome differs between normoweight and obese women. Different processes and pathways among placenta from obese women were dysregulated, including inflammation and immune responses, lipid metabolism, cell death and survival and cancer pathways, vasculogenesis and angiogenesis, and glucocorticoid receptor signaling pathway. Together, this global gene expression profiling approach demonstrates and confirms that maternal obesity creates a unique in utero environment that impairs placental transcriptome.
2017-01-07 | E-MTAB-4541 | biostudies-arrayexpress
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:To explore the influence of maternal choline intake on placental gene expression, we employed whole genome microarray expression profiling to identify genes that were differentially expressed in placental tissues obtained from women consuming two different doses (480 vs. 930 mg/d) of choline throughout the third trimester of pregnancy. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d. Full thickness placental samples were collected at delivery to extract RNA and perform the arrays. Healthy third trimester (gestational week 26-29) pregnant women were randomized to a 12-week choline controlled feeding study. The participants consumed either 480 (n=6) or 930 (n=6) mg choline/d for 12 weeks. Placental samples were obtained at delivery
2012-07-12 | E-GEOD-39290 | biostudies-arrayexpress
Project description:Iron deficiency occurs when iron demands chronically exceed intake, and is particularly prevalent in pregnant women. Iron deficiency during pregnancy poses health risks for the baby. The placenta serves as the interface between a pregnant mother and her baby; thus, maternal iron deficiency may indirectly impact fetal growth and development by altering placental function. In this study, pregnant Sprague-Dawley rats were fed either a low-iron or iron-replete diet starting two weeks before mating. On gestational day 18.5, RNA was collected, and a Clariom S microarray was performed to elucidate differences in gene expression between gestaional day 18.5 placentas isolated from dams fed iron replete or iron deficient diets.
2021-11-10 | GSE163226 | GEO