Fetal and obstetrics manifestations of mitochondrial diseases

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 23, 2024

Abstract During embryonic and neonatal development, mitochondria have essential effects on metabolic energetic regulation, shaping cell fate decisions leading to significant short- long-term offspring health. Therefore, perturbation mitochondrial function can a pathological effect pregnancy. Several shreds of evidence collected in preclinical models revealed that severe dysfunction is incompatible with life or leads critical developmental defects, highlighting the importance correct during embryo-fetal development. The mechanism impairing development unknown may include dysfunctional switch differentiating cells due decreased ATP production altered apoptotic signalling. Given central role fetal typical Mitochondrial Diseases (MDs) should, principle, be detectable However, little known about clinical manifestations MDs In this manuscript, we review suggesting affect highlight maternal outcomes provide wake-up call for targeted genetic diagnosis.

Language: Английский

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Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia

Biology of Sex Differences, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 2, 2021

Abstract Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated women PE during pregnancy up to 2-year postpartum (PP), the reduced uterine perfusion pressure (RUPP) rat model PE. Blockade AT1-AA specific 7 amino acid peptide binding sequence (‘n7AAc’) improves pathophysiology observed RUPP rats; however, long-term effects inhibition PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) ( n = 16), 15), + ‘n7AAc’ 16). Gestational day 14, surgery was performed (144 μg/day) administered via osmotic minipump. At 10-week PP, mean arterial (MAP), glomerular filtration rate (GFR) cardiac functions, mitochondria function assessed. MAP vs. NP (126 ± 4 116 3 mmHg, p < 0.05), but normalized (109 mmHg) 0.05). heart size by ’n7AAc’ Complex IV protein abundance enzymatic activity, along glutamate/malate-driven respiration (complexes I, III, IV), which prevented ‘n7AAc’. not only blood pregnancy, also changes pressure, hypertrophy, mitochondrial PP.

Language: Английский

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Exposure to Obesogenic Environments during Perinatal Development Modulates Offspring Energy Balance Pathways in Adipose Tissue and Liver of Rodent Models

Nutrients, Journal Year: 2023, Volume and Issue: 15(5), P. 1281 - 1281

Published: March 4, 2023

Obesogenic environments such as Westernized diets, overnutrition, and exposure to glycation during gestation lactation can alter peripheral neuroendocrine factors in offspring, predisposing for metabolic diseases adulthood. Thus, we hypothesized that obesogenic the perinatal period reprograms offspring energy balance mechanisms. Four rat models were studied: maternal diet-induced obesity (DIO); early-life induced by postnatal overfeeding; glycation; overfeeding combined with glycation. Metabolic parameters, expenditure, storage pathways visceral adipose tissue (VAT) liver analyzed. Maternal DIO increased VAT lipogenic [NPY receptor-1 (NPY1R), NPY receptor-2 (NPY2R), ghrelin receptor], but also lipolytic/catabolic mechanisms [dopamine-1 receptor (D1R) p-AMP-activated protein kinase (AMPK)] male while reducing NPY1R females. Postnatally overfed animals only exhibited higher NPY2R levels VAT, females presented downregulation. reduces expandability decreasing animals. Regarding liver, D1R was decreased all models, fat accumulation both sexes inflammatory infiltration. The response showed a sexual dysmorphism, glycotoxins led thin-outside-fat-inside phenotype conditions impaired balance, increasing risk

Language: Английский

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Short- and long-term consequences of heat exposure on mitochondrial metabolism in zebra finches (Taeniopygia castanotis)

Oecologia, Journal Year: 2023, Volume and Issue: 201(3), P. 637 - 648

Published: March 1, 2023

Understanding the consequences of heat exposure on mitochondrial function is crucial as mitochondria lie at core metabolic processes, also affecting population dynamics. In adults, metabolism varies with temperature but can depend thermal conditions experienced during development. We exposed zebra finches to two alternative treatments early development: "constant", maintained birds ambient 35 °C from parental pair formation fledglings' independence, while "periodic" heated broods 40 °C, 6 h daily nestling stage. Two years later, we acclimated both experiments 25 for 21 days, before exposing them artificial (40 5 10 days). After conditions, measured red blood cells' using a high-resolution respirometer. found significantly decreased Routine, Oxidative Phosphorylation (OxPhos) and Electron Transport System maximum capacity (ETS) after treatments. addition, "constant" in life showed lower oxygen consumption Proton Leak (Leak) stage treatment adults. Females higher respiration ETS independent treatments, this pattern was reversed OxPhos coupling efficiency (OxCE). Our results show that short-term acclimation involved reduced respiration, reaction adult depends intensity, duration early-life stages. study provides insight into complexity underlying variation raises questions adaptive value long-lasting physiological adjustments triggered by environment.

Language: Английский

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Chronic stress alters hepatic metabolism and thermodynamic respiratory efficiency affecting epigenetics in C57BL/6 mice

iScience, Journal Year: 2024, Volume and Issue: 27(3), P. 109276 - 109276

Published: Feb. 20, 2024

Chronic stress episodes increase metabolic disease risk even after recovery. We propose that persistent detrimentally impacts hepatic reprogramming, particularly mitochondrial function. In male C57BL/6 mice chronic variable (Cvs) reduced energy expenditure (EE) and body mass despite increased intake versus controls. This coincided with decreased glucose metabolism lipid β-oxidation, correlating EE. After Cvs, function revealed thermodynamic efficiency (ƞ-opt) of complex CI, positively blood NEFA inversely Cvs recovery, the flexibility hepatocytes was lost. Reduced CI-driving NAD+/NADH ratio, diminished methylation-related one-carbon cycle components hinted at epigenetic regulation. Although initial DNA methylation differences were minimal they diverged during recovery phase. Here, altered enrichment linked transcriptional networks observed. conclusion, rapidly initiates reprogramming metabolism, supported by lasting modifications.

Language: Английский

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From powerhouse to regulator: The role of mitoepigenetics in mitochondrion-related cellular functions and human diseases

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 218, P. 105 - 119

Published: March 31, 2024

Language: Английский

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Pregestational Prediabetes Induces Maternal Hypothalamic–Pituitary–Adrenal (HPA) Axis Dysregulation and Results in Adverse Foetal Outcomes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5431 - 5431

Published: May 16, 2024

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading adverse outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated effects maternal on HPA axis function postnatal offspring development. Hence, this study pregestational Pre-diabetic (PD) non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from PD NPD groups collected. Markers function, adrenocorticotropin hormone (ACTH) corticosterone, measured all dams pups. Glucose tolerance, insulin gene expressions mineralocorticoid (MR) glucocorticoid (GR) receptors further at birth their developmental milestones. The results demonstrated increased basal concentrations ACTH corticosterone group comparison NPD. Furthermore, show an increase concentrations, disturbed MR GR expression, glucose intolerance resistance assessed via Homeostasis Model Assessment (HOMA) indices compared These observations reveal that associated dysregulation impacting development along impaired handling.

Language: Английский

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Cardiac Molecular Analysis Reveals Aging‐Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation via Hexosamine Biosynthetic Pathway

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 9, 2024

Abstract Age is a prominent risk factor for cardiometabolic disease, often leading to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling dysfunction exclusively resulting from physiological aging remain elusive. Previous research demonstrated age‐related alterations in baboons, analogous humans. The goal of this study identify early preceding adaptations, shedding light on the regulation age‐associated Unbiased transcriptomics left ventricle samples are performed female baboons aged 7.5–22.1 years (human equivalent ≈30–88 years). Weighted‐gene correlation network pathway enrichment analyses performed, with histological validation. Modules transcripts negatively correlated age implicated declined metabolism‐oxidative phosphorylation, tricarboxylic acid cycle, glycolysis, fatty‐acid β‐oxidation. Transcripts positively suggested metabolic shift toward glucose‐dependent anabolic pathways, including hexosamine biosynthetic (HBP). This associated increased glycosaminoglycan synthesis, modification, precursor synthesis via HBP, extracellular matrix accumulation, verified histologically. Upregulated matrix‐induced signaling coincided followed by hypertrophy‐related pathways. Overall, these findings revealed transcriptional metabolism favoring accumulation through HBP before hypertrophy. Unveiling provides potential targets diseases, offering novel insights into mechanisms.

Language: Английский

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Mitophagy Unveiled: Exploring the Nexus of Mitochondrial Health and Neuroendocrinopathy

Journal of Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 74(4)

Published: Nov. 8, 2024

Language: Английский

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Genetic and epigenetic alterations associated with gestational diabetes mellitus and adverse neonatal outcomes

World Journal of Clinical Pediatrics, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 20, 2024

Gestational diabetes mellitus (GDM) is a metabolic disorder, recognised during 24-28 weeks of pregnancy. GDM linked with adverse newborn outcomes such as macrosomia, premature delivery, cardiovascular, and neurological disorders. Recent investigations have focused on the correlation genetic factors β-cell function insulin secretary genes (transcription factor 7 like 2, potassium voltage-gated channel subfamily q member 1, adiponectin etc. ) maternal metabolism gestation leading to GDM. Epigenetic alterations DNA methylation, histone modification, miRNA expression can influence gene play dominant role in feto-maternal pathways. Interactions between environment, resulting differential patterns may lead Researchers suggested that women are more susceptible resistance, which alters intrauterine surroundings, hyperglycemia hyperinsulinemia. modifications affecting neuroendocrine activities, metabolism, increase risk obesity type 2 offspring. There currently no treatment or effective preventive method for GDM, since molecular processes resistance not well understood. The present review was undertaken understand pathophysiology its effects neonatal outcomes. In addition, study epigenetic will provide researchers search predictive biomarkers.

Language: Английский

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