Insights into the regulation of the brain-placental axis (ChIP-seq)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE157552 | GEO | 2023/09/01
REPOSITORIES: GEO
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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:Sexual dimorphism in placental physiology during development affects the functionality of placental adaptation during adverse pregnancy, affecting fetal growth, development, and eventually fetal programming, which have long-term effects on the offspring’s adult life. However, studies focusing on the phenomenon and relationship between sex-specific placental adaptation and consequent altered fetal development are still elusive. Here, we established a prenatal maternal stress model by administering lipopolysaccharide (LPS) to pregnant ICR mice at the mid-gestational stage. To verify the appropriateness of the animal model to study sex differences in the sub-optimal uterus milieu, pregnancy complications were examined. To elucidate global transcriptomic changes occurring in the placenta, total RNA sequencing was performed in female and male placentas. LPS exposure at the mid-gestational stage induced placental inflammation in both sexes. In utero inflammatory conditions resulted in intrauterine fetal growth restriction and impaired placental development in a sex-specific manner depending on the dose of LPS. Sex-biased placental pathology was observed in the junctional zone and the labyrinth layer. Placental transcriptome analysis revealed widespread disparity in protein-coding and long non-coding genes between female and male placentas, presenting the relationship between morphology and function in a sex-specific IUGR model.
2021-08-26 | GSE182462 | GEO
Project description:Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both the mother and fetus. Although some studies have examined these changes in the placenta, the differences resulting from fetal sex remain unelucidated. In this study, we established an intrauterine hyperglycemic model using ICR mice. We collected placental specimens before birth for histological observation using Hematoxylin and Eosin (HE) staining, along with Tandem Mass Tag (TMT) labeled proteomic analysis which was stratified by sex. In both male and female fetuses of the GDM group, body weight and placental weight were significantly lower compared to the control group. Additionally, the placenta-to-body weight ratio was higher, suggesting potential placental insufficiency. Histological analysis revealed smaller sizes and reduced thickness of the junctional zone and labyrinth in diabetic placentas at E18.5, along with ectopic accumulation of spongiotrophoblasts in the labyrinth. When the analysis was not segregated by sex, the GDM group showed 208 upregulated and 225 downregulated proteins in the placenta, primarily within the extracellular matrix and mitochondria. Altered biological processes included cholesterol metabolism and oxidative stress responses. After stratifying by sex, the male subgroup displayed 209 upregulated and 111 downregulated proteins, while the female subgroup exhibited 97 upregulated and 75 downregulated proteins. Among these, 64 differentially expressed proteins showed consistent trends across both sexes, primarily enriched in the JAK-STAT signaling pathway, complement and coagulation cascades, and metabolism-related modifications. The male subgroup showed a heightened tendency for immune-related pathway alterations, whereas the female subgroup manifested changes in branched-chain amino acid metabolism. The intrauterine hyperglycemic environment affects both placental morphology and proteomics, leading to shifts in energy metabolism, oxidative stress responses, and immune processes. Our study suggests that the observed differences in placental protein expression specific to each sex may provide an explanation for the varying impacts of GDM on offspring.
2024-01-17 | PXD048636 |
Project description:The Repressor Element-1 Silencing Transcription (REST) factor is a transcriptional repressor. The aim of this study is to characterize role of REST in placental influences on offspring brain. REST was ablated in mouse placenta by mating mouse carrying floxed (FL) alleles of REST with mouse that expresses Cre recombinase under the control of the promoter of placenta-specific gene Gcm1 (glial cells missing 1). To investigate placental influence on gene expression of adult offspring brain cells, single-nuclei RNA-seq was performed. Data analysis showed that ablation of placental REST significantly impacted specific pathways in choroid plexus and ependymal cells of the offspring brain.
2024-04-19 | GSE237181 | GEO
Project description:We performed deep sequencing of small RNA in the fetal brain and placenta of male and female fetuses to study expression pattern of miRNA and identify key miRNAs that are relevant to gene regulation of the brain-placental axis
2021-08-26 | GSE157554 | GEO
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:There is increasing concern regarding the adverse effects of air pollution on human health, and benzene is a major toxic compound in air pollution. Maternal benzene exposure has been associated with reproductive complications, such as preterm birth, low birth weight, and immunological and neurological complications in the offspring. However, it is poorly understood how benzene induces these complications. Our objective was to establish a full body inhalation mouse model for maternal benzene exposure that mimics clinical phenotypes observed in human populations, and characterize the maternal immune activation and placental response in our model. Here, we report that maternal immune activation triggered by benzene exposure during pregnancy leads to increased resorptions, abnormal placenta development and low birth weight of fetus. More importantly, there is a sexual dimorphic response to benzene exposure in female and male placentas. In the male placenta, the transcriptome changes reveal a more immunologically relevant profile, while females have a metabolically related profile. Furthermore, we discover the sexual dimorphic response could be a consequence of the sexual dimorphism of placenta at baseline, which indicates the significant difference between sexes in terms of the immunological processes in the placenta, both in human and mouse. Therefore, our findings established a benzene exposure mouse model and indicated the sexual dimorphism of placenta, which provides valuable reference for the future pregnancy studies.
2023-07-20 | PXD035085 | Pride
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: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:In this study, the transcriptional repressor REST (Repressor Element 1 Silencing Transcription factor) was ablated in the mouse placenta to investigate molecular and cellular impacts on the offspring brain at different life stages. Ablation of placental REST deregulated several brain metabolites, including glucose and lactate that fuel brain energy, vitamin C (ascorbic acid) that functions in the epigenetic programming of the brain during postnatal development, and glutamate and creatine that help the brain to respond to stress conditions during adult life. Bulk RNA-seq analysis showed that a lack of placental REST persistently altered multiple transport genes, including those related to oxygen transportation in the offspring brain. While metabolic genes were impacted in the postnatal brain, different stress response genes were activated in the adult brain. DNA methylation was also impacted in the adult brain due to the loss of placental REST, but in a sex-biased manner. Single-nuclei RNA-seq analysis showed that specific cell types of the brain, particularly those of the choroid plexus and ependyma, which play critical roles in producing cerebrospinal fluid and maintaining metabolic homeostasis, were significantly impacted due to the loss of placental REST. These cells showed significant differential expression of genes associated with the metabotropic (G coupled protein) and ionotropic (ligand-gated ion channel) glutamate receptors, suggesting an impact of ablation of placental REST on the glutamatergic signaling of the offspring brain. The study expands our understanding of placental influences on the offspring brain.
2024-04-19 | GSE236711 | GEO