Effect of maternal nutrient reduction (MNR) during pregnancy on fetal liver gene expression in baboons (Papio anubis).
Ontology highlight
ABSTRACT:
ORGANISM(S): Papio anubis
PROVIDER: GSE211085 | GEO | 2024/08/11
REPOSITORIES: GEO
Similar Datasets
Project description:We have developed a baboon nonhuman primate (NHP) model of maternal nutrient reduction during fetal development (30% global maternal nutrient reduction, MNR) to evaluate the impact of reduced nutrient availability on primate fetal development. We reported (Antonow-Schlorke et al. PNAS, 2011) that MNR induced major cerebral developmental disturbances at mid gestation (0.5G); however, the impact of MNR at late gestation (0.9G) and the mechanisms mediating these effects have not been determined. We hypothesized that MNR alters developmental trajectories of the fetal prefrontal cortex in the late gestation via miRNA regulation of key transcriptional and translational signaling pathways. Pregnant baboons were fed either ad libitum (control; CON; females n=3; males n=3) or a globally reduced diet (70% of controls; females n=3; males n=3) from 0.16G through 0.9G that produces IUGR (14% reduction in fetal weight). Fetuses were removed by Cesarean section at 0.9G, and prefrontal cortex (PFC) sections collected for analysis. Transcriptome (gene arrays) and small transcriptome (small RNA-Seq) analyses of fetal PFC were performed and gene and miRNA profiles were compared between MNR and CON. We present for the first time transcriptome (GSE42756) and small RNA transcriptome expression profiles of the fetal baboon PFC at 0.9G. Pathway analysis showed that MNR had sex-specific effects on key cellular signaling pathways. We conclude that moderate maternal global nutrient reduction during pregnancy can alter signaling pathways related to nutrient sensing and cell proliferation in the late gestation PFC. In addition, inverse expression of miRNAs known to target genes in these pathways suggests that miRNA mechanisms play a role in these changes.
2018-09-03 | GSE61213 | GEO
Project description:Decreased fetal nutrient delivery is a major cause of developmental neuropathology. Although intrauterine growth restriction spares fetal brain weight, we hypothesized that frontal cortices of fetuses of mothers nutrient restricted during pregnancy, would have decreased ribosomal protein expression. This could potentially result in compromised function since these cellular subunits play a central role in protein synthesis and cellular energetics. Fetal baboons from mothers fed as ad lib controls (CTR) or globally nutrient restricted (MNR) by 30% from 30 - 165 days of gestation (term ~ 184 days in length) were studied. At necropsy, the average body weight of CTR mothers had increased by 11.3% while that of MNR mothers had decreased by 5.5% from before pregnancy. Body weights of MNR fetuses were 17% smaller than CTR fetal weights, but fetal brains were not different. As measured by gene array, 24 of 75 ribosomal protein mRNAs detected were decreased. Protein expression of 7 of 8 ribosomal proteins, assessed by semi-quantitative immunohistochemistry, was significantly (p< 0.05) or marginally (p > 0.05 < 0.1) decreased. The brains of growth-restricted fetuses are often assumed to be normal because of brain growth sparing. However, the present findings regarding ribosomal protein expression, strongly suggest that nutrient restriction in pregnancy, regardless of cause, inhibits protein synthesis in the fetal brain. In addition, these effects may be exacerbated if continued postnatally with possible effects on important protein dependent processes such as long-term memory storage.
2018-12-03 | GSE42756 | GEO
Project description:Background: Poor nutrition during development programs kidney function. No studies on postnatal consequences of decreased perinatal nutrition exist in nonhuman primates (NHP) for translation to human renal disease. Our baboon model of moderate maternal nutrient restriction (MNR) produces intrauterine growth restricted (IUGR) and programs renal fetal phenotype. We hypothesized that the IUGR phenotype persists postnatally influencing responses to a high-fat, high-carbohydrate, high-salt (HFCS) diet. Methods: Pregnant baboons ate chow Control (CON) or 70% of control intake (MNR) from 0.16 gestation through lactation. MNR offspring were IUGR at birth. At weaning, all offspring, (control and IUGR females and males n=3/group) ate chow. At ~3.5 years age, blood, urine, and kidney biopsies were collected before and after a 7-week high HFCS diet challenge. Kidney function, unbiased kidney gene expression, and untargeted urine metabolomics were evaluated. Results: IUGR female and male kidney transcriptome and urine metabolome differed from CON at 3.5 years, prior to HFCS. After the challenge, we observed sex-specific and fetal exposure-specific responses in urine creatinine, urine metabolites, and renal signaling pathways. Conclusions: We previously showed mTOR signaling dysregulation in IUGR fetal kidneys. Before HFCS, gene expression analysis indicated that dysregulation persists postnatally in IUGR females. IUGR male offspring response to HFCS showed uncoordinated signaling pathway responses suggestive of proximal tubule injury. To our knowledge, this is the first study comparing CON and IUGR postnatal juvenile NHP and the impact of fetal and postnatal life caloric mismatch. Perinatal history needs to be taken into account when assessing renal disease risk.
2022-12-01 | GSE149895 | GEO
Project description:Suboptimal intrauterine nutrition predisposes the fetus to central obesity and metabolic syndrome in adult life, suggesting nutritional programming of the fat distribution. However, the underlying mechanisms are not elucidated. We hypothesized that prenatal nutritional deprivation leads to stimulation of adipogenesis, as an adaptive mechanism, in a depot-dependent manner. The induction of adipogenesis is most enhanced in the subcutaneous lower-body depots, followed by the subcutaneous upper-body and visceral adipose tissue depots. Stimulation of adipogenesis may lead to an early consumption of the stem cell pool, and thus, may impair adipose tissue expandability postnatally, which may lead to differences in regional adipose tissue growth. We tested this hypothesis by analyzing global gene expression to identify expression patterns in subcutaneous abdominal, subcutaneous femoral, and omental adipose depots of baboon fetuses that have been altered by nutritional maternal deprivation. Adipose tissue was collected from baboon fetuses at 165 dG from mothers fed control or 30% nutrient-restricted diets (three females and one male in each group). 24 samples, each consisted of pooled total RNA from triplicate wells (6-well plate).
2011-12-16 | E-GEOD-34464 | biostudies-arrayexpress
Project description:Effect of maternal nutrient reduction (MNR) during pregnancy on fetal liver gene expression in baboons (Papio anubis).
| PRJNA868787 | ENA
Project description:Suboptimal intrauterine nutrition predisposes the fetus to central obesity and metabolic syndrome in adult life, suggesting nutritional programming of the fat distribution. However, the underlying mechanisms are not elucidated. We hypothesized that prenatal nutritional deprivation leads to stimulation of adipogenesis, as an adaptive mechanism, in a depot-dependent manner. The induction of adipogenesis is most enhanced in the subcutaneous lower-body depots, followed by the subcutaneous upper-body and visceral adipose tissue depots. Stimulation of adipogenesis may lead to an early consumption of the stem cell pool, and thus, may impair adipose tissue expandability postnatally, which may lead to differences in regional adipose tissue growth. We tested this hypothesis by analyzing global gene expression to identify expression patterns in subcutaneous abdominal, subcutaneous femoral, and omental adipose depots of baboon fetuses that have been altered by nutritional maternal deprivation. Adipose tissue was collected from baboon fetuses at 165 dG from mothers fed control or 30% nutrient-restricted diets (three females and one male in each group).
2011-12-16 | GSE34464 | GEO
Project description:[Original title] In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces disruption of the prostate glands and fibrosis in rhesus monkeys. We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the prostate in rhesus monkey offspring. Dams received 0, 30 or 300 ng/kg TCDD subcutaneously on Day 20 of gestation, and then 5% of the initial dose was injected every 30 days until Day 90 after delivery. The offspring were maintained until reaching sexual maturity, and examined histopathologically. Dose-dependent decreases in the prostate glands and widespread fibrosis were observed in offspring. It is noteworthy that 7 years from the final lactational TCDD exposure, inflammatory cell infiltration and disruption of the prostate glands were also observed. Differential mRNA expression associated with fibrosis, inflammatory response and disruption of cell components were demonstrated by microarray analysis, and up-regulation of TGM4, TGFB1, COL1A1 and MMP2 was confirmed with Real-time PCR. In conclusion, in utero and lactational exposure to TCDD induced dose-proportional prostatic fibrosis, indicating prostatic dysfunction and inducible semen quality reduction in second-generation rhesus monkeys. Dam received 0, 30 or 300 ng/kg TCDD subcutaneously on Day 20 of gestation, and then 5% of the initial dose was injected every 30 days until Day 90 after delivery. The offspring were maintained until reaching sexual maturity, and the prostates from 3 offspring in each group were evalutated by histopathological examination, microarray analysis and Real-time quantitative PCR. Supplementary file: Fold_change comparison results of 'control group vs 30 ng/kg group' and 'control group vs 300 ng/kg group'.
2010-01-27 | E-GEOD-20043 | biostudies-arrayexpress
Project description:[Original title] In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces disruption of the prostate glands and fibrosis in rhesus monkeys. We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the prostate in rhesus monkey offspring. Dams received 0, 30 or 300 ng/kg TCDD subcutaneously on Day 20 of gestation, and then 5% of the initial dose was injected every 30 days until Day 90 after delivery. The offspring were maintained until reaching sexual maturity, and examined histopathologically. Dose-dependent decreases in the prostate glands and widespread fibrosis were observed in offspring. It is noteworthy that 7 years from the final lactational TCDD exposure, inflammatory cell infiltration and disruption of the prostate glands were also observed. Differential mRNA expression associated with fibrosis, inflammatory response and disruption of cell components were demonstrated by microarray analysis, and up-regulation of TGM4, TGFB1, COL1A1 and MMP2 was confirmed with Real-time PCR. In conclusion, in utero and lactational exposure to TCDD induced dose-proportional prostatic fibrosis, indicating prostatic dysfunction and inducible semen quality reduction in second-generation rhesus monkeys.
2010-01-28 | GSE20043 | GEO
Project description:Dysregulation of microRNAs (miRNAs) expression has been implicated in molecular genetics events leading to the progression and development of atherosclerosis. We hypothesized that miRNA expression profiles differ between baboons with low and high serum low-density lipoprotein cholesterol (LDL-C) concentrations in response to diet, and that a subset of these miRNAs regulate genes relevant to dyslipidemia and risk of atherosclerosis. We generated small RNA libraries from baboons differing in their LDL-C response to dietary fat and cholesterol (low LDL-C, n = 3; high LDL-C, n = 3) using liver biopsies collected before and after a high-cholesterol, high-fat (HCHF) challenge diet. We sequenced the libraries using Next-Generation Illumina sequencing methods, analyzed the data using mirTools software and identified 517 baboon miRNAs: 490 homologous to human and 27 novel miRNAs. HCHF diet elicited expression of more miRNAs compared to baseline (chow) diet for both low and high LDL-C baboons. Seventeen miRNAs exhibited significant differential expression in response to HCHF diet in high LDL-C baboons compared to nine miRNAs in low LDL-C baboons. Putative miRNA targets were identified with TargetScan/Base tools. miRNAs significantly targeted more genes in high LDL-C baboons compared to low LDL-C responders. Further, we identified miRNA isomers and other non-coding RNAs that were differentially expressed in response to the challenge diet.Our discovery of differentially expressed baboon miRNAs and their targets is a fundamental step in understanding the role of non-coding RNAs in the modulation of dsylipidemia.
2012-07-14 | E-GEOD-37249 | biostudies-arrayexpress
Project description:Although the mechanisms underlying development of atherosclerosis are not well understood, LDL-C is known to influence expression of endothelial microRNAs (miRNAs) and gene-targets of miRNAs to promote cell senescence. However, the impact of LDL-C on expression of PBMC miRNAs and miRNA targeted genes in response to an atherogenic diet is not known. We hypothesized that miRNA expression profiles differ between baboons with low and high serum low-density lipoprotein cholesterol (LDL-C) concentrations in response to diet, and that microRNA-gene networks in baboons discordant for LDL-Cholesterol We generated small RNA libraries from baboons differing in their LDL-C response to dietary fat and cholesterol (low LDL-C, n = 3; high LDL-C, n = 3) using liver biopsies collected before and after a high-cholesterol, high-fat (HCHF) challenge diet. We sequenced the libraries using Next-Generation Illumina sequencing methods, analyzed the data using mirTools software and identified 517 baboon miRNAs: 490 homologous to human and 27 novel miRNAs. HCHF diet elicited expression of more miRNAs compared to baseline (chow) diet for both low and high LDL-C baboons. Seventeen miRNAs exhibited significant differential expression in response to HCHF diet in high LDL-C baboons compared to nine miRNAs in low LDL-C baboons. Putative miRNA targets were identified with TargetScan/Base tools. miRNAs significantly targeted more genes in high LDL-C baboons compared to low LDL-C responders. Further, we identified miRNA isomers and other non-coding RNAs that were differentially expressed in response to the challenge diet.Our discovery of differentially expressed baboon miRNAs and their targets is a fundamental step in understanding the role of non-coding RNAs in the modulation of dsylipidemia.
2019-03-20 | GSE114722 | GEO