Multigenerational paternal high-fat diet gradually exacerbates environmental stress-induced testicular dysregulated expression of mRNAs in offspring
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE241413 | GEO | 2023/12/22
REPOSITORIES: GEO
Similar Datasets
Project description:PURPOSE: To examine if a parental high fat diet (HFD) influences metabolic health in two generations of offspring, and alters the germ cell (GC) transcriptome. PROCEDURE: GC-eGFP Sprague Dawley rats were weaned onto HFD (45% fat) or Control Diet (CD; 10% fat). After metabolic testing, founders (F0) were bred with controls, establishing the F1 generation. Germ cells from F0 males were isolated and their RNA sequenced. F1 rats were bred with control rats at 17 weeks to generate F2 offspring. FINDINGS: HFD resulted in 9.7% and 14.7% increased weight in male and female F0 respectively. F1 offspring of HFD mothers were heavier than controls. F1 daughters of HFD-fed males were also heavier. F2 male offspring derived from HFD-fed maternal grandfathers were 7.2% heavier, and exhibited increases of 31% in adiposity, 97% in plasma leptin and 300% in luteinising hormone to testosterone ratio. HFD exposure did not alter the F0 GC transcriptome. CONTROLS: Matched CD was consumed by all animals not consuming the HFD. Animals were compared to a parallel cohort of CD rats. CONCLUSIONS: HFD consumption by maternal grandfathers results in a disrupted metabolic phenotype in grandsons. This effect is not mediated by alterations to the GC transcriptome.
2016-08-17 | GSE80721 | GEO
Project description:It is known that both maternal and paternal health/disease can influence the early development and later metabolic homeostasis of the offspring. We investigated whether maternal exercise during gestation alone could protect the offspring from the adverse effects of either maternal or paternal obesity induced by high-fat diet (HFD). To understand the underlying mechanisms we performed transcriptomics, whole-genome DNA methylation and targeted DNA methylation analysis at the metabolic master regulator, peroxisome proliferator-activated receptor g coactivator-1a (Pgc-1a) promoter in the adult offspring skeletal muscle. Both maternal and paternal HFD resulted in impaired glucose tolerance in the offspring at 9 months of age. Maternal exercise during gestation completely mitigated this metabolic impairment induced by either maternal or paternal HFD. Adult offspring exposed to either maternal or paternal HFD without exercise during gestation had skeletal muscle transcriptional profiles enriched in genes regulating inflammation and immune responses, whereas maternal exercise resulted in a transcriptional profile that was more similar to control offspring from normal chow fed parents. Changes in promoter and CpG DNA methylation were detected between the groups but did not explain the transcriptional changes. Maternal HFD increased methylation of the Pgc-1α promoter at CpG -260, which was prevented by maternal exercise. Paternal HFD did not affect the methylation of the Pgc-1α promoter. These findings demonstrate the negative consequences of maternal and paternal obesity for the offspring’s metabolic outcomes later in life and the clear benefits of maternal exercise during gestation. The mechanisms involve transcriptional regulation of skeletal muscle likely through multiple types of epigenetic modifications.
2021-07-30 | GSE144111 | GEO
Project description:It is known that both maternal and paternal health/disease can influence the early development and later metabolic homeostasis of the offspring. We investigated whether maternal exercise during gestation alone could protect the offspring from the adverse effects of either maternal or paternal obesity induced by high-fat diet (HFD). To understand the underlying mechanisms we performed transcriptomics, whole-genome DNA methylation and targeted DNA methylation analysis at the metabolic master regulator, peroxisome proliferator-activated receptor g coactivator-1a (Pgc-1a) promoter in the adult offspring skeletal muscle. Both maternal and paternal HFD resulted in impaired glucose tolerance in the offspring at 9 months of age. Maternal exercise during gestation completely mitigated this metabolic impairment induced by either maternal or paternal HFD. Adult offspring exposed to either maternal or paternal HFD without exercise during gestation had skeletal muscle transcriptional profiles enriched in genes regulating inflammation and immune responses, whereas maternal exercise resulted in a transcriptional profile that was more similar to control offspring from normal chow fed parents. Changes in promoter and CpG DNA methylation were detected between the groups but did not explain the transcriptional changes. Maternal HFD increased methylation of the Pgc-1α promoter at CpG -260, which was prevented by maternal exercise. Paternal HFD did not affect the methylation of the Pgc-1α promoter. These findings demonstrate the negative consequences of maternal and paternal obesity for the offspring’s metabolic outcomes later in life and the clear benefits of maternal exercise during gestation. The mechanisms involve transcriptional regulation of skeletal muscle likely through multiple types of epigenetic modifications.
2021-07-30 | GSE144109 | GEO
Project description:This study aimed to assess PFAS distribution and lung proteome changes in CD-1 offspring after gestational and lactational exposure to PFOS, PFOA, PFHxS, or a PFAS mix. A secondary aim was to evaluate how maternal exposure to a high fat diet (HFD) affected the latter endpoints. Pregnant CD-1 mice received PFOA, PFOS, PFHxS (1 mg/kg), a PFAS mix (1 mg/kg each), or vehicle. Dams were fed standard diet (SD) or high fat diet (HFD), and PFAS were administered from gestation day 1 to postnatal day 20. At PND 21, lung PFAS concentration was measured using LC-MS/MS, and proteomic analysis was conducted. Results from LC-MS/MS analysis showed a significant overall difference in PFOS, PFOA, and PFHxS levels and the treatment groups with PFHxS concentration were significantly higher compared to PFOS and PFOA. Proteomic analysis determined female pups exposed to maternal HFD Mix (Mix HFD female) and PFOS (PFOS HFD female) had the most differentially expressed proteins followed by PFOS SD male, Mix SD female, and Mix SD male. Canonical pathways like EIF2 signaling, mTOR signaling, and mitochondrial dysfunction were differentially modulated. This study provides insights into PFAS distribution, the molecular mechanism, biomarkers on the neonatal lung in animal models following perinatal exposure.
2023-12-06 | MSV000093587 | MassIVE
Project description:Maternal multi-generational high fat diet (HFD) exposure increases the offspring HCC incidence
| PRJNA482414 | ENA
Project description:Cadmium (Cd) is a toxic heavy metal and ubiquitous environmental endocrine disruptor. Previous studies on Cd-induced damage to male fertility mainly focus on the structure and function of testis, and semen quality. Nevertheless, to date, no studies have investigated the effects of Cd exposure on sperm epigenetic inheritance and intergenerational inheritance. In our study, we systematically revealed the changes in sperm tRNA-derived small RNAs (tsRNA) profiles and found that 14 tsRNAs (9 up-regulated and 5 down-regulated) were significantly altered after Cd exposure. Bioinformatics of tsRNA-mRNA-pathway interactions revealed that the altered biological functions mainly were related to ion transmembrane transport, lipid metabolism and cell membrane system. In addition, we focused on two stages of early embryo development and selected two organs to study the impact of these changes on cell membrane system, especially mitochondrion and lysosome, two typical membrane-enclosed organelles. Surprisingly, we found that the content of mitochondrion was significantly decreased in 2-cell stage, whereas remarkably increased in the morula stage. The contents of mitochondrion and lysosome were significantly increased in the testes of 6-days offspring and livers of adult offspring, whereas remarkably decreased in the testes of adult offspring. This provides a possible basis to further explore the effects of paternal Cd exposure on offspring health.
2021-12-15 | GSE190236 | GEO
Project description:Parental exposure to environmental stress can result in an increased diseases risk in the offspring. Although literature on maternal contribution to hereditary diseases are growing, the paternal contribution is frequently underrecognized. Since human studies reported that 80% of transmitted mutations arise in the paternal germline, it is crucial to understand the mechanism underlying the paternally inherited genome instability. Ionizing radiation (IR) is a major source of mutagenesis through inducing DNA double-strand breaks (DSBs). Here, we used sex-separated C. elegans mutants to investigate the paternal contribution to IR-induced transgenerational effects. Specifically, we found that paternal exposure to IR leads to a transgenerational embryonic lethality, and this effect is only observed when the radiation exposure occurred close to the time of fertilization. In the offspring of the irradiated males (F1 generation), we detected various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement, and aneuploidy. These phenotypes are attributed to the usage of two error-prone repair machinery, the polymerase-theta mediated end joining (TMEJ) and the non-homologous End Joining (NHEJ). Surprisingly, depletion of a human histone H1.0 ortholog, HIS-24, can significantly rescue this transgenerational embryonic lethality. Moreover, this rescue effect is associated with the downregulation of heterochromatin marker histone 3 lysine 9 di-methylation (H3K9me2), and the knocking-down of heterochromatin protein, HPL-1, could mimic the rescue effect of HIS-24 depletion. We also noticed that removal of the histone H1 and heterochromatin marker could activate the error-free repair machinery, Homologous Recombination repair (HR), thus improving the viability of the offspring carrying paternally inherited DNA damage. Altogether, our work sheds light on the importance of paternal radiation exposure on the health of offspring. In addition, our work establishes a previously unknown mechanism underlying the transgenerational genome instability and provides a potential therapeutic target for preventing the hereditary diseases caused by paternal radiation exposure.
2022-10-18 | PXD031873 | Pride
Project description:Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it remains unclear whether phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a specific ligand-receptor interaction and thereby enable pharmacological interrogation of the offspring phenotype, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that paternal exposure to chronic nicotine induced a broad protective response to xenobiotic exposure in the next generation. This effect manifested as increased survival following an injection of toxic levels of nicotine, was specific to male offspring, and was only observed after these offspring were first acclimated to low levels of nicotine for a week. Importantly, offspring xenobiotic resistance was documented not only for toxic nicotine challenge, but also for toxic cocaine challenge, indicating that paternal nicotine exposure reprograms offspring to become broadly resistant to environmental toxins. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, and we found that isolated hepatocytes displayed upregulation of enzymes that metabolize xenobiotics. Taken together, our data show that paternal nicotine exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.
2017-02-02 | GSE92240 | GEO
Project description:Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it generally remains unclear whether the phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a known ligand-receptor interaction and thereby enable pharmacological interrogation of the specificity of the offspring response, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that chronic paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in the next generation. This effect manifested as increased survival following an injection of toxic levels of either nicotine or of cocaine, was specific to male offspring, and was only observed after offspring were first acclimated to sublethal doses of nicotine or cocaine. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, accompanied by hepatic upregulation of genes involved in xenobiotic metabolism. Surprisingly, this protective effect could also be induced by paternal exposure to a nicotinic receptor antagonist as well as to nicotine, suggesting that paternal xenobiotic exposure, rather than nicotinic receptor signaling, is likely to be responsible for programming of offspring drug resistance. Taken together, our data show that paternal drug exposure can induce a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.
2017-02-01 | GSE94059 | GEO
Project description:The global rise in obesity has revitalized a search to understand genetic, and in particular, epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced Inter-Generational Metabolic Reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as two days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, de-silencing chromatin state-defined transcriptional units in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3 dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system regulates obesity-susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution. RNA-seq on Drosophila embryos and sperm samples fed medium and high sugar.
2014-12-04 | E-GEOD-62668 | biostudies-arrayexpress