Paternal obesity and epigenetic inheritance of breast cancer: The role of systemic effects and transmission to the second generation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE161831 | GEO | 2020/11/20
REPOSITORIES: GEO
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Project description:Transcriptome analysis of gastrocnemius muscle RNA samples from exercise and sedentary ancestries Early life and pre-conception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or M-bM-^@M-^\exercise ancestry,M-bM-^@M-^] on morphological and metabolic phenotypes in multiple generations of mouse offspring. F0 C57BL/6 mice were exposed to voluntary exercise or sedentary lifestyle and bred with like-exposed mates to produce an F1 generation. F1 mice of both ancestries were sedentary and sacrificed at 8 wk or bred with littermates to produce an F2 generation, which was also sedentary and sacrificed at 8 wk. Small, but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance, and muscle gene expression. F1 EX females were heavier than F1 SED females, but F1 SED females had higher absolute tibialis anterior and omental fat masses. Serum insulin was lower in F1 SED females compared to F1 EX females. F2 EX females had impaired glucose tolerance compared to F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g., F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1M-NM-1, Adipoq, and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring. We analyzed RNA from 10 males each from exercise and sedentary ancestries over 2 generations of offspring (F1 and F2)
2012-08-30 | E-GEOD-40469 | biostudies-arrayexpress
Project description:Transcriptome analysis of gastrocnemius muscle RNA samples from exercise and sedentary ancestries Early life and pre-conception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or “exercise ancestry,” on morphological and metabolic phenotypes in multiple generations of mouse offspring. F0 C57BL/6 mice were exposed to voluntary exercise or sedentary lifestyle and bred with like-exposed mates to produce an F1 generation. F1 mice of both ancestries were sedentary and sacrificed at 8 wk or bred with littermates to produce an F2 generation, which was also sedentary and sacrificed at 8 wk. Small, but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance, and muscle gene expression. F1 EX females were heavier than F1 SED females, but F1 SED females had higher absolute tibialis anterior and omental fat masses. Serum insulin was lower in F1 SED females compared to F1 EX females. F2 EX females had impaired glucose tolerance compared to F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g., F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1α, Adipoq, and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring.
2012-08-30 | GSE40469 | GEO
Project description:Adult female Wistar rats (about 220g) obtained from a breeding colony were mated and fed either a protein sufficient (PS) or protein restricted (PR) diet (n = 6 per dietary group) during F0 pregnancy which provided an increase in energy of approximately 25% compared to the diet fed to the breeding colony (2018S). During lactation dams were fed AIN93G and litters were standardisied to 8 offspring within 24 hours of birth with a bias towards females. Offpsring were weaned onto AIN93M at postnatal day 28 and F1 and F2 females were mated on postnatal day 70 (n = 6 per F0 dietary group). F1 and F2 dams were fed the PS diet during pregnancy and AIN93G during lactation. Offspring were weaned onto AIN93M. On postnatal day 70 unmated female offspring were fasted for 12 hours then sacrificed for hepatic transcritpome analysis by microarray. Expression of 1,684 genes differed by at least 2 fold between adult female F1 offspring of F0 dams from both dietary groups. 1680 genes were altered in F2 offspring and 2,065 genes altered in F3 offspring. Expression of 113 genes was altered in all three generations. Of these, 47% showed directionally opposite differences between generations. Gene ontology analysis revealed clear differences in the pathways altered in each generation. F1 and F2 offspring of F0 dams fed a PR diet showed impaired fasting glucose homeostasis. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) expression was elevated in F1 and F2 offspring from F0 PR dams, but decreased in F3, compared to PS offspring
2011-06-01 | E-MEXP-3205 | biostudies-arrayexpress
Project description:This study examined the potential transgenerational actions of the herbicide atrazine. The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease, increased frequency of tumor development in males and females (predominately mammary tumors), early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations and a lean phenotype in males and females involving a reduced adipocyte size, decreased body mass index (BMI) and reduced adiposity. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified. A comparison of control versus atrazine lineage sperm identified 519 DMRs (p<10-6) for the F1 generation, 431 DMR (p<10-5) for the F2 generation, and 958 DMR (p<10-9) for the transgenerational F3 generation sperm.
2017-08-08 | GSE98683 | GEO
Project description:The current study was designed to use a rodent model to determine if exposure to the chemotherapy drug ifosfamide during puberty can induce altered phenotypes and disease in the grand-offspring of exposed individuals through epigenetic transgenerational inheritance. Numerous toxicant exposures during critical developmental windows can have generational impacts through this non-genetic inheritance mechanism. Pathologies such as delayed pubertal onset, kidney disease and multiple pathologies were observed to be significantly more frequent in the F1 generation offspring of ifosfamide lineage females. The F2 generation grand-offspring ifosfamide lineage males had transgenerational pathology phenotypes of early pubertal onset and reduced testis pathology. Reduced levels of anxiety were observed in both males and females from the exposure lineage in the transgenerational F2 generation grand-offspring. Differential DNA methylated regions (DMRs) were also identified in chemotherapy and control lineages sperm in the F1 and F2 generations. The transgenerational alterations in sperm epigenetics provides a molecular mechanism for the ancestral impacts of chemotherapy. Therefore, chemotherapy exposure can impact pathology and disease susceptibility in subsequent generations.
2022-11-30 | GSE217141 | GEO
Project description:The goals of this study are to compare genome-wide DNA methylation levels in young and aged oocytes,and to investigate the transgenerational inheritance of methylome profiles in oocytes during natural aging. We apply a novel protocol of rapamycin to overcome the DNA methylation drift associated with oocyte aging. 8-week-old female mice were injected intraperitoneally with rapamycin or vehicle for 40 weeks. At the end of the experiment, females (48 weeks, F0) were paired with young adult (~4 mo old) males to produce F1 offspring (OF1 and ORaF1). An F2 generation (OF2 and ORaF2) resulted from mating F1 female at 44~48 weeks of age with young adult males. To generate YF1 and YF2 as normal control (offspring of young mother), we mated females (~8 weeks) with young adult males. Then we collect oocytes (F0,F1 and F2 generations)，sperm ( F1 and F2 generations) and hippocampus (F1 female offspring) from different groups to investigate the transgenerational inheritance of DNA methylome profiles associated with oocyte aging by the single cell whole-genome methylation sequencing (sc-WGBS). We found that oocytes from aged mother exhibited increased DNA methylation levels in CpG sites. Maternal aging related methylome changes can be inherited transgenerationally though oocyte to the germ line of F1 and F2 offspring. The application of rapamycin during the course of oocyte aging could reverse these DNA methylation alterations, and it can ameliorate several neurobehavioral aging trails that were in observed in aged oocyte offspring. WGBS-seq on DNA from hippocampal tissue revealed a number of differentially methylated (P<0.05) genes in OF1 and ORaF1 compared with YF1, and some of the enriched pathways were associated with aging process, such as PI3K-Akt signaling pathway (akin to transcriptional alterations above), MAPK signaling and Ras signaling pathway .
2022-12-31 | GSE164139 | GEO
Project description:Female and male rats of an outbred female Sprague Dawley rats were administered daily intraperitoneal injections of vinclozolin (100 mg/kg BW/day), or DDT (25 mg/kg BW/day) or dimethyl sulfoxide (DMSO) in oil (1 µl/kg BW/day vehicle). Treatment lineages are designated “control” or “vinclozolin” or “DDT” lineages. The gestating female rats treated were designated as the F0 generation. The offspring of the F0 generation rats were the F1. Non-littermate females and males aged 70-90 days from F1 generation of control, vinclozolin or DDT were bred to obtain F2 generation offspring. The F2 generation rats were similarly bred to obtain the F3 generation offspring. Individuals were maintained for 120 days and euthanized for sperm collection. Sperm from multiple individual rats was pooled into single samples. For the control samples, 2 pools were made using 6 animals and 1 pool with 5 animals. For the DDT samples, 3 pools were mady using 4 animals. For the Vinclozolin samples, 3 pools were made using 4 animals. Genomic DNA was isolated and histone chromatin immunoprecipitation with genomic DNA was performed. Each pooled sample received a separate index primer. NGS was performed at the WSU Spokane Genomics Core using Ilumina HiSeq 2500 with a PE50 application, with a read size of approximately 50 bp and approximately 35 million reads per pool.
2018-01-12 | GSE106125 | GEO
Project description:The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa to alter metabolism in the F1 and F2 generation offspring White adipose tissue mRNA expression profiling of F2-female offspring from F0-founders fed either a chow or a chronic HFD challenged. Adult females were challenged or not a high-fat diet for 12 weeks. White adipose tissue was dissected at an endpoint experiment. Rats were subjected to 4 hours fasting prior to anesthesia with pentobarbital and tissue collection.
2017-01-01 | GSE65182 | GEO
Project description:For many behaviours studied at the phenotypic level, we have little or no idea of where to start searching for “candidate” genes: the transcriptome provides such a starting point. Here we consider transcriptomic changes associated with oviposition in the parasitoid wasp Nasonia vitripennis. Oviposition is a key behaviour, as females are faced with a variety of decisions that will impact offspring fitness. These include choosing between hosts of differing quality, as well as deciding on clutch size and offspring sex ratio. We compared the whole-body transcriptomes of resting or ovipositing female Nasonia using a “DEEP-Sage” gene expression approach on the Illumina sequencing platform. Single 2-day old mated Nasonia vitripennis females (ASymC strain) were isolated in a glass vial and provided with a single host to produce F1 daughters. Eight 2-day old mated F1 females were subsequently provided with three hosts to produce the F2 test females. We randomly selected one host from each F1 female, and isolated 16 2-day old mated F2 test females in glass tubes, of which eight were randomly allocated to the oviposition treatment and eight to the resting treatment. We provided the test females with a single host for 24 hours as pre-treatment to facilitate egg development. We then discarded the pre-treatment hosts and gave each female a piece of chromatography paper soaked in honey solution for a further 24 hours. For the experiment, we transferred the females to 1.5 mL Eppendorf tubes that contained a single host for the oviposition experiment, or were empty for the resting treatment. After 60 mins, females were flash-frozen in liquid nitrogen and stored on dry-ice until the addition of RNAlater-ICE (Ambion, Austin, TX, USA) after which they were transferred to -20C. All females in the oviposition treatment were observed to have commenced ovipositing. We pooled the F2 test females from each F1 mother according to treatment, generating a total of eight pooled samples per treatment (consisting of 8 females per pool) for RNA isolation and sequencing.
2013-07-22 | E-GEOD-43352 | biostudies-arrayexpress
Project description:Rodent studies have indicated that gestational and perinatal bisphenol A (BPA) exposure increase the risk of developing breast cancer during adulthood. In contrast, some dietary compounds such as genistein (GEN) and indole 3-carbinol (I3C) present potential protective effects against inducing hormone-dependent cancers, including that of the mammary gland. Thus, we aimed to evaluate the role of these dietary compounds on early mammary gland development and carcinogenesis in female Sprague-Dawley offspring. Pregnant Sprague-Dawley (SD) rats were treated with BPA at 25 or 250µg/kg b.w./day by gavage from gestational day (GD) 10 to 21 with or without dietary GEN (250 mg/kg chow, ~5.5 mg/kg b.w./day) or I3C (2000 mg/kg chow, ~45.0 mg/kg b.w./day). At post-natal day (PND) 21, some female offspring from different litters were euthanized for mammary gland development and gene expression analyses while other female offspring received a single dose of N-methyl-N-nitrosourea (MNU) for mammary carcinogenesis initiation. The findings this study indicated the prenatal exposure to BPA, GEN and I3C did not significantly alter ductal elongation, number of terminal end buds (TEB) or cell proliferation, and estrogen receptor alpha (ER-α) immunostaining expression in epithelial mammary cells at PND 21. BPA treatment modulated the expression of several genes, but these changes were not associated with a dose dependent response. Dietary GEN and I3C treatment causally and consistent with the mammary gland structures outcomes. Besides, maternal BPA exposure associated with dietary GEN and I3C did not alter the susceptibility to the mammary cancer development in adulthood when the carcinogen was administered in a window of immature mammary gland development.
2016-06-03 | GSE68973 | GEO