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Expression Data from Young Uteroplacental Insufficiency-induced Low Birth Weight Adult Guinea Pig Offspring

ABSTRACT: We aimed to gain mechanistic insights into the impact of uteroplacental insufficiency upon hepatic cholestrol metabolism pathways in young adult offspring.Uterine artery ablation-induced low birth weight (LBW) and normal birth weight (NBW) male and female guinea pig offspring were fed a control diet from weaning until postnatal day 150. Analysis of whole hepatic transcriptome results identified that between LBW and NBW offspring livers, 51 (29 up-regulated and 22 down-regulated) and 31 (8 up-regulated and 23 down-regulated) genes were differentially expressed in males and females respectively (fold change| >= 2 and p-value < 0.05). KEGG pathway analysis of these differentially expressed genes revealed that “Cholesterol metabolism” was an enriched pathway in LBW males but not females (p<0.05).

ORGANISM(S): Cavia porcellus

PROVIDER: GSE161124 | GEO | 2020/11/10

REPOSITORIES: GEO

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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.

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Expression Data from Young Uteroplacental Insufficiency-induced Low Birth Weight Adult Guinea Pig Offspring

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