Exposure to lipopolysaccharide induces sexually dimorphic placental adaptation by modifying placental efficiency, morphogenesis, and gene expression
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182462 | GEO | 2021/08/26
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:Fetal growth restriction (FGR) develops when fetal nutrient availability is compromised and increases the risk for perinatal complications and predisposes for offspring obesity, diabetes and cardiovascular disease later in life. Emerging evidence implicates changes in placental function in altered fetal growth and the subsequent development of adult disease. The susceptibility for disease in response to an adverse intrauterine environment differs distinctly between boys and girls, with girls typically having better outcomes. Here, we test the hypothesis that regulation of the placental transcriptome by moderate nutrient reduction is dependent on fetal sex. We used a non-human primate model of FGR in which maternal global food intake is reduced by 30% starting at gestational day (GD) 30. At GD 165 (term = GD 183) placental genome expression profiling was carried out followed by bioinformatics including pathway and network analysis. Surprisingly, there was no coordinated placental molecular response to decreased nutrient availability when analyzing the data without accounting for fetal sex. In contrast, female placentas exhibited a highly coordinated response that included up-regulation of genes in networks, pathways and functional groups related to programmed cell death and down-regulation of genes in networks, pathways and functional groups associated with cell proliferation. These changes were not apparent in the male placentas. Our data support the concept that female placentas initiate complex adaptive responses to an adverse intrauterine environment, which may contribute to increased survival and better pregnancy outcomes in girls. Total RNA obtained from 165dGA control female (n=3), control male (n=3), nutrient restricted female (n=3), and nutrient restricted male (n=3) pregnancies.
2013-12-06 | E-GEOD-40878 | biostudies-arrayexpress
Project description:Fetal growth restriction (FGR) develops when fetal nutrient availability is compromised and increases the risk for perinatal complications and predisposes for offspring obesity, diabetes and cardiovascular disease later in life. Emerging evidence implicates changes in placental function in altered fetal growth and the subsequent development of adult disease. The susceptibility for disease in response to an adverse intrauterine environment differs distinctly between boys and girls, with girls typically having better outcomes. Here, we test the hypothesis that regulation of the placental transcriptome by moderate nutrient reduction is dependent on fetal sex. We used a non-human primate model of FGR in which maternal global food intake is reduced by 30% starting at gestational day (GD) 30. At GD 165 (term = GD 183) placental genome expression profiling was carried out followed by bioinformatics including pathway and network analysis. Surprisingly, there was no coordinated placental molecular response to decreased nutrient availability when analyzing the data without accounting for fetal sex. In contrast, female placentas exhibited a highly coordinated response that included up-regulation of genes in networks, pathways and functional groups related to programmed cell death and down-regulation of genes in networks, pathways and functional groups associated with cell proliferation. These changes were not apparent in the male placentas. Our data support the concept that female placentas initiate complex adaptive responses to an adverse intrauterine environment, which may contribute to increased survival and better pregnancy outcomes in girls.
2013-12-06 | GSE40878 | 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:We used microarrays to determine the transcriptional profiles of placental tissue obtained from women who smoked during pregnancy and from women who did not smoke during pregnancy. Fetal growth restriction is a frequent complication in mothers who smoke cigarettes during pregnancy. To evaluate novel pathways that regulate fetal growth affected by mothers who smoke, we isolated placental mRNA from smoking mothers with severe fetal growth restriction and compared them by microarray analysis to non-smoking mothers with appropriately grown fetuses. Bioinformatics analysis revealed distinct transcriptional patterns in the placentas of smoking mothers when compared to placentas from control non-smoking women. Analyses of the top upregulated and downregulated genes revealed several gene products such as secreted frizzled related protein 1 that was markedly upregulated in the placentas from women who smoked cigarettes during pregnancy. Total RNA was isolated from placental specimens obtained at time of delivery. RNA was hybridized to Affymetrix arrays, and analyzed.
2016-08-08 | E-GEOD-71931 | biostudies-arrayexpress
Project description:We used microarrays to determine the transcriptional profiles of placental tissue obtained from women who smoked during pregnancy and from women who did not smoke during pregnancy. Fetal growth restriction is a frequent complication in mothers who smoke cigarettes during pregnancy. To evaluate novel pathways that regulate fetal growth affected by mothers who smoke, we isolated placental mRNA from smoking mothers with severe fetal growth restriction and compared them by microarray analysis to non-smoking mothers with appropriately grown fetuses. Bioinformatics analysis revealed distinct transcriptional patterns in the placentas of smoking mothers when compared to placentas from control non-smoking women. Analyses of the top upregulated and downregulated genes revealed several gene products such as secreted frizzled related protein 1 that was markedly upregulated in the placentas from women who smoked cigarettes during pregnancy.
2016-08-08 | GSE71931 | GEO
Project description:Background: The placenta is vital for fetal development and its contributions to various developmental issues, such as pregnancy complications, fetal growth restriction, and maternal exposure, have been extensively studied in mice. Contrary to popular belief, the placenta forms mainly from fetal tissue; therefore, it has the same biological sex as the fetus it supports. However, while placental function is linked to increased risks of pregnancy complications and neurodevelopmental diseases in male offspring in particular, the sex-specific epigenetic (e.g., DNA methylation) and transcriptomic features of the late-gestation mouse placenta remain largely unknown.Methods: We collected male and female mouse placentas at late gestation (E18.5, n = 3/sex) and performed next-generation sequencing to identify genome-wide sex-specific differences in transcription and DNA methylation. Results: Our sex-specific analysis revealed 358 differentially expressed genes (DEGs) on autosomes, which were associated with signaling pathways involved in transmembrane transport and the responses to viruses and external stimuli. X chromosome DEGs (n = 39) were associated with different pathways, including those regulating chromatin modification and small GTPase-mediated signal transduction. Sex-specific differentially methylated regions (DMRs) were more common on the X chromosomes (n = 3756) than on autosomes (n = 1705). Interestingly, while most X chromosome DMRs had higher DNA methylation levels in female placentas and tended to be included in CpG dinucleotide-rich regions, 73% of autosomal DMRs had higher methylation levels in male placentas and were distant from CpG-rich regions. Several sex-specific DEGs were correlated with sex-specific DMRs. A subset of the sex-specific DMRs present in late-stage placentas were already established in mid-gestation (E10.5) placentas, while others were acquired later in placental development.Conclusion: Our study provides comprehensive lists of sex-specific DEGs and DMRs that collectively cause profound differences in the DNA methylation and gene expression profiles of late-gestation mouse placentas. Our results demonstrate the importance of incorporating sex-specific analyses into epigenetic and transcription studies to enhance the accuracy and comprehensiveness of their conclusions and help address the significant knowledge gap regarding how sex differences influence placental function.
2023-12-30 | GSE252283 | GEO
Project description:Background: The placenta is vital for fetal development and its contributions to various developmental issues, such as pregnancy complications, fetal growth restriction, and maternal exposure, have been extensively studied in mice. Contrary to popular belief, the placenta forms mainly from fetal tissue; therefore, it has the same biological sex as the fetus it supports. However, while placental function is linked to increased risks of pregnancy complications and neurodevelopmental diseases in male offspring in particular, the sex-specific epigenetic (e.g., DNA methylation) and transcriptomic features of the late-gestation mouse placenta remain largely unknown.Methods: We collected male and female mouse placentas at late gestation (E18.5, n = 3/sex) and performed next-generation sequencing to identify genome-wide sex-specific differences in transcription and DNA methylation. Results: Our sex-specific analysis revealed 358 differentially expressed genes (DEGs) on autosomes, which were associated with signaling pathways involved in transmembrane transport and the responses to viruses and external stimuli. X chromosome DEGs (n = 39) were associated with different pathways, including those regulating chromatin modification and small GTPase-mediated signal transduction. Sex-specific differentially methylated regions (DMRs) were more common on the X chromosomes (n = 3756) than on autosomes (n = 1705). Interestingly, while most X chromosome DMRs had higher DNA methylation levels in female placentas and tended to be included in CpG dinucleotide-rich regions, 73% of autosomal DMRs had higher methylation levels in male placentas and were distant from CpG-rich regions. Several sex-specific DEGs were correlated with sex-specific DMRs. A subset of the sex-specific DMRs present in late-stage placentas were already established in mid-gestation (E10.5) placentas, while others were acquired later in placental development.Conclusion: Our study provides comprehensive lists of sex-specific DEGs and DMRs that collectively cause profound differences in the DNA methylation and gene expression profiles of late-gestation mouse placentas. Our results demonstrate the importance of incorporating sex-specific analyses into epigenetic and transcription studies to enhance the accuracy and comprehensiveness of their conclusions and help address the significant knowledge gap regarding how sex differences influence placental function.
2023-12-30 | GSE252281 | GEO
Project description:As susceptibility to many adult disorders originates in utero, we here hypothesized that fetal sex influences gene expression in placental cells and produces functional differences in human placentas. We found that fetal sex differentially affects gene expression in a cell-phenotype dependent manner among all four placental cell-phenotypes studied: cytotrophoblasts, syncytiotrophoblasts, arterial endothelial cells and venous endothelial cells. The markedly enriched pathways in males were identified to be signaling pathways for graft-versus-host disease as well as the immune and inflammatory systems, both supporting the hypothesis that there is reduced maternal-fetal compatibility for male fetuses. Our study is the first microarray study investigating sexual dimorphism in purified and characterized somatic cells from a single human tissue, the placenta, that underlines the importance of considering fetal sex as an independent variable in any work using human placenta. Arterial and venous endothelial cells were isolated from eight different placentas, four of each sex. A total of ten placentas were used for isolation of cytotrophoblasts and six for syncytiotrophoblasts, with equal numbers from each sex.
2013-10-01 | E-GEOD-44368 | biostudies-arrayexpress
Project description:This study aims to identify genome-wide placental DNA differential methylation positions (DMPs) in fetal overgrowth and the associations with fetal growth factors, leptin and adiponectin. In the Shanghai Birth Cohort, we studied 30 pairs of placentals of large-for-gestational-age (LGA, birth weight>90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25th-75th percentiles, control) newborns matched by sex and gestational age. Placental DNA methylations were measured by the Illumina Infinium Human Methylation-EPIC BeadChip. Cord blood insulin, C-peptide, proinsulin, IGF-1, IGF-2, leptin and adiponectin concentrations were measured. We identified 543 DMPs (397 hypermethylated, 146 hypomethylated) comparing LGA vs. OGA at false discovery rate <5% and absolute methylation difference >0.05 adjusting for placental cell type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. We validated a hyper-methylated gene - cadherin 13 (CDH13) reported in a previous epigenome-wide association study, and validated a newly discovered differentially (hyper-)methylated gene -visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (47 LGA-control pairs). Pathway analysis did not detect any statistically significant pathway correcting for multiple tests. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while other observed biomarkers were not. Fetal overgrowth was associated with a large number of altered placental gene DNA methylations. The study provides robust evidence suggesting that placental CDH13 and VSX1 genes are hyper-methylated in LGA. Placental gene methylation was correlated with cord blood biomarker for adiponectin, but not for leptin and fetal growth factors.
2022-12-31 | GSE204977 | GEO