Maternal Western-style diet alters the transcriptome of chemically induced mammary tumors in female offspring rats
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE96520 | GEO | 2018/10/12
SECONDARY ACCESSION(S): PRJNA378885
REPOSITORIES: GEO
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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
Project description:Background & Aims: The influences of the maternal diet during gestation has been suggested to be involved in the development of different aspects of the metabolic syndrome. In our mouse model we characterised the role of maternal western diet in the development of non-alcoholic fatty liver disease (NAFLD) in the offspring. Methods: Female mice were fed either a western (W) or low-fat control (L) semi-synthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. Results: Male offspring exposed to prenatal western style diet and to a post-weaning W diet (WW) showed hepatomegaly combined with increased hepatic cholesterol and triglycerides accumulation, compared to LW offspring. This was associated with up-regulation of de novo lipid synthesis and dysregulation of beta oxidation and lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. Histological analysis supported the presence of steatohepatitis in the WW offspring. In addition alterations in DNA methylation in key metabolic genes (Ppara, Insig, Fasn) were detected. Conclusion: Maternal dietary fat intake during critical developmental phases programs susceptibility to liver disease in mouse offspring. This was mediated by shifts in lipid metabolism and inflammatory response. Long lasting epigenetic changes may underlie this dysregulation 4 groups of 6 male mouse were analysed , 1 experimental and 1 biological outlier was excluded , so n=6,5,5,6 in the 4 groups (LL,LW,WL,WW)
2014-01-21 | E-GEOD-44901 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease is strongly associated with obese and type 2 diabetes. It has been reported that an oxidized cholesterol, 7-ketocholesterol (7KC) might cause inflammatory response in macrophages and plasma 7KC concentration were higher in patients with cardiovascular diseases or diabetes. Therefore, we have decided to test whether small amount of 7KC in diet might induce hepatic steatosis and inflammation in two types of obese models. We found that addition of 0.01% 7KC either in chow diet (CD, regular chow diet with 1% cholesterol) or western type diet (WD, high fat diet with 1% cholesterol) accelerated hepatic neutral lipid accumulation by Oil Red O staining. Importantly, by lipid extraction analysis, it has been recognized that triglyceride rather than cholesterol species was significantly accumulated in CD+7KC compared to CD as well as in WD+7KC compared to WD. Immunostaining revealed that macrophages infiltration was increased in CD+7KC compared to CD and also in WD+7KC compared to WD. These phenotypes were accompanied by inducing inflammatory response and downregulating fatty acid oxidation. Furthermore, RNA sequence analysis demonstrated that 7KC reduced expression of genes which related to autophagy process. Levels of LC3-II protein were decreased in WD+7KC compared to WD. Similarly, we have confirmed the effect of 7KC on acceleration of steatohepatitis in db/db mice model. Collectively, our study has demonstrated that small amount of dietary 7KC contributed to accelerate hepatic steatosis and inflammation in obese mice models.
2021-01-15 | GSE159234 | GEO
Project description:Background & Aims: The influences of the maternal diet during gestation has been suggested to be involved in the development of different aspects of the metabolic syndrome. In our mouse model we characterised the role of maternal western diet in the development of non-alcoholic fatty liver disease (NAFLD) in the offspring. Methods: Female mice were fed either a western (W) or low-fat control (L) semi-synthetic diet before and during gestation and lactation. At weaning, male offspring were assigned either the W or the L diet, generating four experimental groups: WW, WL, LW and LL offspring. Biochemical, histological and epigenetic indicators were investigated at 29 weeks of age. Results: Male offspring exposed to prenatal western style diet and to a post-weaning W diet (WW) showed hepatomegaly combined with increased hepatic cholesterol and triglycerides accumulation, compared to LW offspring. This was associated with up-regulation of de novo lipid synthesis and dysregulation of beta oxidation and lipid storage. Elevated hepatic transaminases and increased expression of Tnfa, Cd11, Mcp1 and Tgfb underpin the severity of liver injury. Histological analysis supported the presence of steatohepatitis in the WW offspring. In addition alterations in DNA methylation in key metabolic genes (Ppara, Insig, Fasn) were detected. Conclusion: Maternal dietary fat intake during critical developmental phases programs susceptibility to liver disease in mouse offspring. This was mediated by shifts in lipid metabolism and inflammatory response. Long lasting epigenetic changes may underlie this dysregulation
2014-01-21 | GSE44901 | GEO
Project description:Maternal Western-style diet alters the transcriptome of chemically induced mammary tumors in female offspring rats
| PRJNA378885 | ENA
Project description:We report how human hepatocytes with PNPLA3 148I and 148M variants (rs738409) engrafted in the livers of chimeric mice respond to different durations of hypercaloric western style diet (WD). To determine how WD affected human and mouse gene expression we performed RNA-sequencing (RNA-seq) on livers from fasting mice.
2021-02-13 | GSE166693 | GEO
Project description:The linkage between nutrition and cancer prevention is an intriguing concept that is gaining widespread support based on epidemiological and animal studies. Multiple mechanisms likely underlie dietary protection against cancer, with effects influenced by target tissue response, cell-cell interactions and developmental context. Given the negative correlation between breast cancer incidence and intake of soy foods by Asian women, and the increasing consumption of soy protein-based formula by infants in the Western world, we have studied soy protein isolate (SPI) used in most infant formula as a paradigm to evaluate diet as a risk factor in a rodent model of mammary cancer. We previously demonstrated that lifetime exposure to dietary SPI reduced the incidence of N-methyl-N-nitrosourea-induced mammary tumors in young adult rats relative to those fed the control diet Casein (CAS). This protection was associated with increased tumor suppressor PTEN and decreased Wnt signaling component expression in mammary epithelial cells at postnatal day (PND) 50 prior to carcinogen insult. To identify early events contributing to mammary tumor suppression by diet, we used Affymetrix RAE230A GeneChips containing 14280 probe sets and the GeneSpring Robust Multi-array program to analyze genomic profiles of mammary glands of prepubertal (PND21) rats lifetime exposed to SPI or CAS. Experiment Overall Design: Female SD rats are exposed to either casein/soy protein isolate based AIN-93G diet since gestation day 4 till weaning. Whole mammary gland were harvested for the gene analysis by microarray.
2009-08-07 | E-GEOD-12217 | biostudies-arrayexpress
Project description:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (pM-bM-^IM-$0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) as six weeks pre-treatment before mating, as well as during gestation and lactation. Offspring were sacrificed at postnatal week two, livers were removed and RNA samples were subjected to gene expression profiling.
2013-11-27 | E-GEOD-46359 | biostudies-arrayexpress