Maternal high-fat-diet alters lactation-specific miRNA expression and programs the DNA methylome in female offspring
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE158170 | GEO | 2020/09/18
REPOSITORIES: GEO
Similar Datasets
Project description:Early-life exposure to high-fat diet (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic and cognitive parameters in young adult offspring mice. To identify early-programming mechanisms in hippocampus, we developed a multi-omics strategy in male and female offspring. Maternal HF induced a transient increased body weight at weaning, a mild glucose intolerance only in 3-month-old male mice with no change in plasma metabolic parameters in adult male and female offspring. Behavioral alterations revealed by Barnes maze test were observed both in 6-month-old male and female mice. Multi-omics strategy unveiled sex-specific transcriptomic and proteomic modifications in the hippocampus of adult offspring. These studies, that were confirmed by regulon analysis, showing that, although genes whose expression was modified by maternal HF were different between sexes, the main pathways affected were similar with mitochondria and synapses as main hippocampal targets of maternal HF. The effects of maternal HF reported here may help to better characterize sex-dependent molecular pathways involved in cognitive disorders and neurodegenerative diseases.
2024-01-26 | PXD045639 | Pride
Project description:We show that traumatic stress experienced by males in early postnatal life impairs memory in their offspring, blocks long-term potentiation (LTP) and favors long-term depression (LTD). These effects are accompanied by suppression of key molecular pathways involved in neuronal plasticity both at rest and after acute stress. Male mice were exposed to chronic traumatic stress in early postnatal life and were later bred to naM-CM-/ve females to produce second-generation offspring. Memory performance was evaluated in the offspring, and synaptic plasticity was examined in the hippocampus and the amygdala, brain areas important for memory formation. The two groups tested were 1: offspring of fathers which were stressed (MSUS - maternal separation unpredictable stress) and 2: offspring of non-stressed fathers (control). Genome-wide gene expression in hippocampus of these two groups was assessed at rest (this study) and after acute stress.
2014-07-01 | E-GEOD-47846 | biostudies-arrayexpress
Project description:We show that traumatic stress experienced by males in early postnatal life impairs memory in their offspring, blocks long-term potentiation (LTP) and favors long-term depression (LTD). These effects are accompanied by suppression of key molecular pathways involved in neuronal plasticity both at rest and after acute stress. Male mice were exposed to chronic traumatic stress in early postnatal life and were later bred to naM-CM-/ve females to produce second-generation offspring. Memory performance was evaluated in the offspring, and synaptic plasticity was examined in the hippocampus and the amygdala, brain areas important for memory formation. The two groups tested were 1: offspring of fathers which were stressed (MSUS - maternal separation unpredictable stress) and 2: offspring of non-stressed fathers (control). Genome-wide gene expression in hippocampus of these two groups was assessed at rest and after acute stress (this study).
2014-07-01 | E-GEOD-47847 | biostudies-arrayexpress
Project description:Exposure to intrauterine heat stress during late gestation affects offspring performance into adulthood. However, underlying mechanistic links between thermal insult in fetal life and postnatal outcomes are not completely understood. Utilizing RNA Sequencing, this study characterized the mammary gland transcriptome of heifers that were gestated under maternal conditions of heat stress or cooling, i.e., in utero heat stressed (HT) vs. in utero cooled (CL). Mammary tissues were collected from three HT and three CL heifers during their first lactation.
2018-08-30 | GSE119216 | GEO
Project description:Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.
2023-11-04 | GSE246534 | GEO
Project description:Exposure to intrauterine heat stress during late gestation affects offspring performance into adulthood. However, underlying mechanistic links between thermal insult in fetal life and postnatal outcomes are not completely understood. Utilizing Reduced Representation Bisulfite Sequencing, this study evaluated DNA methylation of liver and mammary gland of bull calves and heifers that were gestated under maternal conditions of heat stress or cooling, i.e., in utero heat stressed (HT) vs. in utero cooled (CL). Liver samples from bull calves (CT = 5 and HT = 4) were collected at birth while mammary gland samples from heifers (CT = 3 and HT = 3) were collected during their first lactation.
2018-09-05 | GSE119445 | GEO
Project description:Accumulating researches suggest that exposure to abnormal environment in the uterus causes chronic diseases in future life. High intrauterine estradiol level is a major characteristic of in vitro fertilization. Here, we explored the potential neurodevelopment harm and behavior disorder of prenatal high estradiol exposure.
2017-06-27 | GSE100456 | GEO
Project description:Early life nutritional imbalances are risk factors for metabolic dysfunctions in adulthood, but the effects of perinatal exposure to high versus low protein diets are poorly understood. We exposed C57BL/6 offspring to a high protein/low carbohydrate (HP/LC) or low protein/high carbohydrate (LP/HC) diet during gestation and lactation, and measured metabolic phenotypes between birth and ten months of age in male offspring. Perinatal HP/LC and LP/HC exposures resulted in a decreased ability to clear glucose in the offspring, with reduced baseline insulin and glucose levels in the LP/HC group and a reduced insulin response post-glucose challenge in the HP/LC group. The LP/HC diet group also showed reduced weight at birth and at weaning age, whereas the HP/LC offspring showed an increased weight at weaning and increased adiposity after 5 months of age. Gene expression profiling of hypothalamic and liver tissues indicated alterations of diverse molecular pathways by both diets. Specifically, hypothalamic transcriptome and pathway analyses indicate perturbations of MAPK and hedgehog signaling, processes associated with neural restructuring and transmission, and phosphate metabolism by perinatal protein imbalances. Liver transcriptome data revealed changes in purine and phosphate metabolism, hedgehog signaling, and circadian rhythm pathways. Our results support that maternal protein imbalances perturb molecular pathways in central and peripheral metabolic tissues and predispose offspring to metabolic dysfunctions.
2018-10-01 | GSE120548 | GEO
Project description:In utero environment is crucial to ensure normal development of the fetus and to program metabolic health throughout the life. Beside macronutrients, the role of micronutrients, including vitamin D, begins to be explore. The aim of this study was to decipher the impact of maternal vitamin D deficiency (VDD), in normal and high-fat (HF) diet context, on adipose tissue metabolism and energy homeostasis in offspring, considering sex-specific responses. Body weight, energy expenditure, and spontaneous activity was differential impacted in juvenile male and female offspring born from VDD mice. In adulthood, a HF diet combined with maternal VDD disrupted glucose homeostasis and adiposity in male offspring but not in females. Such phenotypes were associated to different transcriptomic profiles in adipose tissue, which could be related to differential modulation of plasma 17b-estradiol concentrations. Thus, maternal VDD sex-dependently modulated metabolic fate of the offspring, especially when associated with HF diet in adulthood.
2022-06-22 | GSE206372 | GEO
Project description:Background: Assisted Reproductive Technologies (ART) - treatments to allow parenthood to couples facing fertility issues- have allowed the birth of > 5 million babies worldwide. Notwithstanding most of ART children are healthy at birth, several studies reported that ART may affect early-life experience causing permanent changes in fetal programming and, consequently, leading to increased predisposition to metabolic disorders in adulthood. Currently, the metabolic health status of ART children has been poorly investigated and it will take decades before large-scale population studies will be implemented. Studies on animal models indicated impaired in utero development of ART conceptuses. Relevantly, our preliminary data showed hypomethylation of liver from ART foetuses, which may contribute to the fetal programming of adult diseases. Regarding adult ART offspring, obesity, glucose intolerance and lipid accumulation in the liver have been previously described in mouse model, indicative of increased risk to develop metabolic disorders. However, little is known on the pathophysiological mechanism behind the metabolic abnormalities in ART offspring. In this context, this study investigated the influence of ART on the function of the liver, a major organ involved in the maintenance of metabolic homeostasis.
Methods: To assess the influence of ART on liver functions, proteomic analysis was carried out on adult liver from 4 months old offspring developed following Embryo Transfer (ET), in vitro culture (IVC) and blastomere biopsy (BB). Control (CTR) consisted of naturally conceived offspring. Then, to verify whether and how changes in liver proteome were associated with perturbation of the metabolic status of adult offspring, general growth and physiological parameters (e.g. glucose tolerance, insulin resistance, plasmatic levels of interleukin 6, triglycerides and total cholesterol) were assessed.
Results: Proteomic analysis of adult liver showed deregulated expression of proteins involved in lipid, carbohydrate and energy metabolism as well as cellular processes in adult offspring developed following BB, IVC and ET. Characterization of metabolic phenotype of adult offspring revealed increased body weight in ART offspring, glucose intolerance in BB, IVC, ET males and BB females, insulin resistance on BB offspring, low plasmatic level of Interleukin-6 in BB, IVC, ET males and high level of triglycerides and total cholesterol in BB females vs CTR which are phenotypic manifestation of liver disfunctions and core symptoms of metabolic syndrome.
Conclusion: Our study showed DE of proteins involved in metabolic and cellular processes, indicative of impaired hepatic functions which may contribute to the onset and progression of various diseases (e.g. NASH, NAFLD, hepatocarcinoma) in mouse offspring developed following ART. Moreover, impaired hepatic metabolism was associated with obesity, glucose intolerance, insulin resistance and dyslipidaemia which are core symptoms of metabolic syndrome and risk factor for diabetes and cardiovascular diseases in adult ART offspring. Thus, we provide evidence of Assisted Reproductive Technologies is a risk factor for perturbation of hepatic proteome, associated with the increased predisposition to liver diseases and metabolic syndrome in adulthood.
2020-05-14 | MSV000085413 | MassIVE