Non-communicable Diseases In Offspring Research Articles

Maternal androgen excess inhibits fetal cardiomyocytes proliferation through RB-mediated cell cycle arrest and induces cardiac hypertrophy in adulthood

PurposeMaternal hyperandrogenism during pregnancy is associated with adverse gestational outcomes and chronic non-communicable diseases in offspring. However, few studies are reported to demonstrate the association between maternal androgen excess and cardiac health in offspring. This study aimed to explore the relation between androgen exposure in utero and cardiac health of offspring in fetal and adult period. Its underlying mechanism is also illustrated in this research.MethodsPregnant mice were injected with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was collected for metabolite and morphological analysis. The hearts from adult offspring were also collected for morphological and qPCR analysis. H9c2 cells were treated with 75 μM androsterone. Immunofluorescence, flow cytometry, qPCR, and western blot were performed to observe cell proliferation and explore the underlying mechanism.ResultsIntrauterine exposure to excessive androgen led to thinner ventricular wall, decreased number of cardiomyocytes in fetal offspring and caused cardiac hypertrophy, compromised cardiac function in adult offspring. The analysis of steroid hormone metabolites in fetal heart tissue by ultra performance liquid chromatography and tandem mass spectrometry showed that the content of androgen metabolite androsterone was significantly increased. Mechanistically, H9c2 cells treated with androsterone led to a significant decrease in phosphorylated retinoblastoma protein (pRB) and cell cycle-related protein including cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin D1 (CCND1) in cardiomyocytes. This resulted in cell cycle arrest at G1–S phase, which in turn inhibited cardiomyocyte proliferation.ConclusionTaken together, our results indicate that in utero exposure to DHT, its metabolite androsterone could directly decrease cardiomyocytes proliferation through cell cycle arrest, which has a life-long-lasting effect on cardiac health. Our study highlights the importance of monitoring sex hormones in women during pregnancy and the follow-up of cardiac function in offspring with high risk of intrauterine androgen exposure.

The effects of Elateriospermum tapos against obese maternal rat in mitigating obesity development among their adult female offspring

Background: Maternal obesity is a metabolic disorder described by chronic inflammation and dyslipidemia and influences non-communicable diseases in offspring. Elateriospermum tapos is a plant containing high alpha-linolenic acid with antiobesity effect. Objectives: This study was aim to investigate the effect of E. tapos supplementation in obese rat prior pregnancy on the female offspring's body weight, liver and kidney profile, and histological changes of heart, liver, kidney, and retroperitoneal white adipose tissue (RpWAT). Materials and Methods: Thirty female Sprague Dawley rats were used in this study. Six rats were assigned to dams normal diet group fed with standard chow diet. The remaining rats were fed with high-fat and cafeteria diet (HFCD) to generate obesity for 5 weeks. The obese rats were further divided into 4 groups; group1; Dams Negative Control (DNC, normal saline only), group 2; Dams Positive Control (DPC, Orlistat drug 200mg/kg), Dams Treatment 1 (DTX1, E. tapos seed 200 mg/kg) and Dams Treatment 2 (DTX2, E. tapos shell 200mg/kg) extracts for 6 weeks daily prior to mating. The weaning offspring were then designated into 6 groups according to their dam's group (n = 6/group). The offspring were culled at 12th week of age in order to have their blood sample and organs. Results: Adult offspring from DTX2 group showed a decrease in weight gain, alanine aminotransferase, and creatinine level compared to adult offspring from DNC. Histological examination showed that liver and RpWAT of offspring from DTX1 and DTX2 groups were comparable with normal diet group, indicating that the extracts were capable in reversing the high fat diet effect to the organ. Conclusion: E. tapos shell supplementation was effective in reducing the development of obesity with no harmful effect among adult female rat offspring.

Maternal diabetes mellitus and the origin of non-communicable diseases in offspring: the role of epigenetics.

Offspring of diabetic mothers are susceptible to the onset of metabolic syndromes, such as type 2 diabetes and obesity at adulthood, and this trend can be inherited between generations. Genetics cannot fully explain how the noncommunicable disease in offspring of diabetic mothers is caused and inherited by the next generations. Many studies have confirmed that epigenetics may be crucial for the detrimental effects on offspring exposed to the hyperglycemic environment. Although the adverse effects on epigenetics in offspring of diabetic mothers may be the result of the poor intrauterine environment, epigenetic modifications in oocytes of diabetic mothers are also affected. Therefore, the present review is focused on the epigenetic alterations in oocytes and embryos of diabetic mothers. Furthermore, we also discuss initial mechanistic insight on maternal diabetes mellitus causing alterations of epigenetic modifications.

Maternal Western-Style High Fat Diet Induces Sex-Specific Physiological and Molecular Changes in Two-Week-Old Mouse Offspring

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 (p≤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.