Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 14, 2023

Abstract Although more studies are demonstrating that a father’s environment can influence child health and disease, the molecular mechanisms underlying non-genetic inheritance remain unclear. It was previously thought sperm exclusively contributed its genome to egg. More recently, association have shown various environmental exposures including poor diet, toxicants, stress, perturbed epigenetic marks in at important reproductive developmental loci were associated with offspring phenotypes. The cellular routes underlie how transmitted fertilization, resist reprogramming embryo, drive phenotypic changes only now beginning be unraveled. Here, we provide an overview of state field intergenerational paternal mammals present new insights into relationship between embryo development three pillars inheritance: chromatin, DNA methylation, non-coding RNAs. We evaluate compelling evidence sperm-mediated transmission retention embryo. Using landmark examples, discuss sperm-inherited regions may escape impact via implicate transcription factors, chromatin organization, transposable elements. Finally, link paternally functional pre- post-implantation Understanding factors will permit greater understanding related origins disease.

Язык: Английский

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Air pollution exposure and cardiometabolic risk

The Lancet Diabetes & Endocrinology, Год журнала: 2024, Номер 12(3), С. 196 - 208

Опубликована: Фев. 2, 2024

Язык: Английский

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Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

Environmental Science & Technology, Год журнала: 2024, Номер 58(5), С. 2166 - 2184

Опубликована: Янв. 26, 2024

Environmental pollutants have been recognized for their ability to induce various adverse outcomes in both the environment and human health, including inflammation, apoptosis, necrosis, pyroptosis, autophagy. Understanding these biological mechanisms has played a crucial role risk assessment management efforts. However, recent identification of ferroptosis as form programmed cell death emerged critical mechanism underlying pollutant-induced toxicity. Numerous studies demonstrated that fine particulates, heavy metals, organic substances can trigger ferroptosis, which is closely intertwined with lipid, iron, amino acid metabolism. Given growing evidence linking severe diseases such heart failure, chronic obstructive pulmonary disease, liver injury, Parkinson's Alzheimer's cancer, it imperative investigate ferroptosis. In this review, we comprehensively analyze pathways intricate signaling molecules elucidate integration into driving braking axes. Furthermore, discuss potential hazards associated organs four representative animal models. Finally, provide an outlook on future research directions strategies aimed at preventing By enhancing our understanding novel developing effective preventive measures, mitigate effects environmental safeguard health.

Язык: Английский

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Parkinson’s Disease is Predominantly a Genetic Disease

Journal of Parkinson s Disease, Год журнала: 2024, Номер 14(3), С. 467 - 482

Опубликована: Март 26, 2024

The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene Contursi kindred 1997 indisputably confirmed genetic cause subset Parkinson’s disease (PD) patients. Currently, variants one seven established PD genes or strongest known risk factor gene, GBA1, are identified ∼15% patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues research that suggest an important - some cases even predominant role genetics aetiology, including familial clustering, high rates monogenic selected populations, complete penetrance with certain forms. At first sight, steep increase prevalence exceeding other neurodegenerative diseases may argue against etiology. Notably, principal contribution is conferred by LRRK2 GBA1 and, both cases, characterized overall late age-related penetrance. addition, polygenic plays considerable PD. However, it likely that, majority patients, complex interplay aging, genetic, environmental, epigenetic factors leads to development.

Язык: Английский

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Gene–environment interactions in human health

Nature Reviews Genetics, Год журнала: 2024, Номер 25(11), С. 768 - 784

Опубликована: Май 28, 2024

Язык: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Язык: Английский

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Environmental Mycotoxins: A Potential Etiological Factor for Neurodegenerative Diseases?

Toxicology, Год журнала: 2025, Номер 511, С. 154056 - 154056

Опубликована: Янв. 13, 2025

Язык: Английский

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Multi-omics approaches for understanding gene-environment interactions in noncommunicable diseases: techniques, translation, and equity issues

Human Genomics, Год журнала: 2025, Номер 19(1)

Опубликована: Янв. 31, 2025

Non-communicable diseases (NCDs) such as cardiovascular diseases, chronic respiratory cancers, diabetes, and mental health disorders pose a significant global challenge, accounting for the majority of fatalities disability-adjusted life years worldwide. These arise from complex interactions between genetic, behavioral, environmental factors, necessitating thorough understanding these dynamics to identify effective diagnostic strategies interventions. Although recent advances in multi-omics technologies have greatly enhanced our ability explore interactions, several challenges remain. include inherent complexity heterogeneity multi-omic datasets, limitations analytical approaches, severe underrepresentation non-European genetic ancestries most omics which restricts generalizability findings exacerbates disparities. This scoping review evaluates landscape data related NCDs 2000 2024, focusing on advancements integration, translational applications, equity considerations. We highlight need standardized protocols, harmonized data-sharing policies, advanced approaches artificial intelligence/machine learning integrate study gene-environment interactions. also opportunities translating insights (GxE) research into precision medicine strategies. underscore potential advancing enhancing patient outcomes across diverse underserved populations, emphasizing fairness-centered strategic investments build local capacities underrepresented populations regions.

Язык: Английский

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Genetics of chronic respiratory disease

Nature Reviews Genetics, Год журнала: 2024, Номер 25(8), С. 534 - 547

Опубликована: Март 6, 2024

Язык: Английский

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The demethylase ALKBH5 mediates ZKSCAN3 expression through the m6A modification to activate VEGFA transcription and thus participates in MNNG-induced gastric cancer progression

Journal of Hazardous Materials, Год журнала: 2024, Номер 473, С. 134690 - 134690

Опубликована: Май 21, 2024

Язык: Английский

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