scholarly journals Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations during Mammalian Development

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1559 ◽  
Author(s):  
Louis Legoff ◽  
Shereen Cynthia D’Cruz ◽  
Sergei Tevosian ◽  
Michael Primig ◽  
Fatima Smagulova
Keyword(s):  
Molecular Mechanisms ◽  
Disease Risk ◽  
Current Knowledge ◽  
Epigenetic Inheritance ◽  
Epigenetic Alterations ◽  
Transgenerational Inheritance ◽  
Mammalian Development ◽  
Genetic Studies ◽  
Salient Points ◽  
Chromatin Proteins

Genetic studies traditionally focus on DNA as the molecule that passes information on from parents to their offspring. Changes in the DNA code alter heritable information and can more or less severely affect the progeny’s phenotype. While the idea that information can be inherited between generations independently of the DNA’s nucleotide sequence is not new, the outcome of recent studies provides a mechanistic foundation for the concept. In this review, we attempt to summarize our current knowledge about the transgenerational inheritance of environmentally induced epigenetic changes. We focus primarily on studies using mice but refer to other species to illustrate salient points. Some studies support the notion that there is a somatic component within the phenomenon of epigenetic inheritance. However, here, we will mostly focus on gamete-based processes and the primary molecular mechanisms that are thought to contribute to epigenetic inheritance: DNA methylation, histone modifications, and non-coding RNAs. Most of the rodent studies published in the literature suggest that transgenerational epigenetic inheritance through gametes can be modulated by environmental factors. Modification and redistribution of chromatin proteins in gametes is one of the major routes for transmitting epigenetic information from parents to the offspring. Our recent studies provide additional specific cues for this concept and help better understand environmental exposure influences fitness and fidelity in the germline. In summary, environmental cues can induce parental alterations and affect the phenotypes of offspring through gametic epigenetic inheritance. Consequently, epigenetic factors and their heritability should be considered during disease risk assessment.

scholarly journals The role of cigarette smoke-induced epigenetic alterations in inflammation

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Dandan Zong ◽  
Xiangming Liu ◽  
Jinhua Li ◽  
Ruoyun Ouyang ◽  
Ping Chen
Keyword(s):  
Cigarette Smoke ◽  
Gene Transcription ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Epigenetic Alterations ◽  
Rna Sequences ◽  
Non Coding Rna ◽  
Near Future

Abstract Background Exposure to cigarette smoke (CS) is a major threat to human health worldwide. It is well established that smoking increases the risk of respiratory diseases, cardiovascular diseases and different forms of cancer, including lung, liver, and colon. CS-triggered inflammation is considered to play a central role in various pathologies by a mechanism that stimulates the release of pro-inflammatory cytokines. During this process, epigenetic alterations are known to play important roles in the specificity and duration of gene transcription. Main text Epigenetic alterations include three major modifications: DNA modifications via methylation; various posttranslational modifications of histones, namely, methylation, acetylation, phosphorylation, and ubiquitination; and non-coding RNA sequences. These modifications work in concert to regulate gene transcription in a heritable fashion. The enzymes that regulate these epigenetic modifications can be activated by smoking, which further mediates the expression of multiple inflammatory genes. In this review, we summarize the current knowledge on the epigenetic alterations triggered by CS and assess how such alterations may affect smoking-mediated inflammatory responses. Conclusion The recognition of the molecular mechanisms of the epigenetic changes in abnormal inflammation is expected to contribute to the understanding of the pathophysiology of CS-related diseases such that novel epigenetic therapies may be identified in the near future.

scholarly journals Genetic control of non-genetic inheritance in mammals: state-of-the-art and perspectives

2020 ◽  
Vol 31 (5-6) ◽  
pp. 146-156 ◽  
Author(s):  
A. Tomar ◽  
R. Teperino
Keyword(s):  
Molecular Mechanisms ◽  
Disease Risk ◽  
Association Studies ◽  
Epigenetic Inheritance ◽  
Genetic Effects ◽  
Genome Wide Association Studies ◽  
Missing Heritability ◽  
Indirect Genetic Effects ◽  
Genome Wide ◽  
Main Determinants

Abstract Thought to be directly and uniquely dependent from genotypes, the ontogeny of individual phenotypes is much more complicated. Individual genetics, environmental exposures, and their interaction are the three main determinants of individual’s phenotype. This picture has been further complicated a decade ago when the Lamarckian theory of acquired inheritance has been rekindled with the discovery of epigenetic inheritance, according to which acquired phenotypes can be transmitted through fertilization and affect phenotypes across generations. The results of Genome-Wide Association Studies have also highlighted a big degree of missing heritability in genetics and have provided hints that not only acquired phenotypes, but also individual’s genotypes affect phenotypes intergenerationally through indirect genetic effects. Here, we review available examples of indirect genetic effects in mammals, what is known of the underlying molecular mechanisms and their potential impact for our understanding of missing heritability, phenotypic variation. and individual disease risk.

scholarly journals Transgenerational epigenetic inheritance of diabetes risk as a consequence of early nutritional imbalances

2015 ◽  
Vol 75 (1) ◽  
pp. 78-89 ◽  
Author(s):  
Josep C. Jimenez-Chillaron ◽  
Marta Ramon-Krauel ◽  
Silvia Ribo ◽  
Ruben Diaz
Keyword(s):  
Environmental Factors ◽  
Physical Inactivity ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Epigenetic Inheritance ◽  
Transgenerational Inheritance ◽  
Parental Nutrition ◽  
Inheritance Of Diabetes ◽  
Genetic And Environmental Factors

In today's world, there is an unprecedented rise in the prevalence of chronic metabolic diseases, including obesity, insulin resistance and type 2 diabetes (T2D). The pathogenesis of T2D includes both genetic and environmental factors, such as excessive energy intake and physical inactivity. It has recently been suggested that environmental factors experienced during early stages of development, including the intrauterine and neonatal periods, might play a major role in predisposing individuals to T2D. Furthermore, several studies have shown that such early environmental conditions might even contribute to disease risk in further generations. In this review, we summarise recent data describing how parental nutrition during development increases the risk of diabetes in the offspring. We also discuss the potential mechanisms underlying transgenerational inheritance of metabolic disease, with particular emphasis on epigenetic mechanisms.

scholarly journals Epigenetic dysregulation in various types of cells exposed to extremely low-frequency magnetic fields

2021 ◽  
Author(s):  
Gianfranco Giorgi ◽  
Brunella Del Re
Keyword(s):  
Magnetic Fields ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Low Frequency ◽  
Cell Types ◽  
International Agency ◽  
Epigenetic Alterations ◽  
Extremely Low Frequency ◽  
Number Of Publications

AbstractEpigenetic mechanisms regulate gene expression, without changing the DNA sequence, and establish cell-type-specific temporal and spatial expression patterns. Alterations of epigenetic marks have been observed in several pathological conditions, including cancer and neurological disorders. Emerging evidence indicates that a variety of environmental factors may cause epigenetic alterations and eventually influence disease risks. Humans are increasingly exposed to extremely low-frequency magnetic fields (ELF-MFs), which in 2002 were classified as possible carcinogens by the International Agency for Research on Cancer. This review summarizes the current knowledge of the link between the exposure to ELF-MFs and epigenetic alterations in various cell types. In spite of the limited number of publications, available evidence indicates that ELF-MF exposure can be associated with epigenetic changes, including DNA methylation, modifications of histones and microRNA expression. Further research is needed to investigate the molecular mechanisms underlying the observed phenomena.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Lighting a path: genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 239-252
Keyword(s):  
Molecular Mechanisms ◽  
Protein Localization ◽  
Regulation Of Gene Expression ◽  
Neuronal Cell ◽  
Mrna Splicing ◽  
Genetic Mutations ◽  
Scaffolding Proteins ◽  
Molecular Processes ◽  
Genetic Studies ◽  
Novel Treatments

In this review, we outline critical molecular processes that have been implicated by discovery of genetic mutations in autism. These mechanisms need to be mapped onto the neurodevelopment step(s) gone awry that may be associated with cause in autism. Molecular mechanisms include: (i) regulation of gene expression; (ii) pre-mRNA splicing; (iii) protein localization, translation, and turnover; (iv) synaptic transmission; (v) cell signaling; (vi) the functions of cytoskeletal and scaffolding proteins; and (vii) the function of neuronal cell adhesion molecules. While the molecular mechanisms appear broad, they may converge on only one of a few steps during neurodevelopment that perturbs the structure, function, and/or plasticity of neuronal circuitry. While there are many genetic mutations involved, novel treatments may need to target only one of few developmental mechanisms.

Alcohol Consumption and Risk of Uterine Fibroids

2020 ◽  
Vol 20 (4) ◽  
pp. 247-258 ◽  
Author(s):  
Hajra Takala ◽  
Qiwei Yang ◽  
Ahmed M. Abd El Razek ◽  
Mohamed Ali ◽  
Ayman Al-Hendy
Keyword(s):  
Alcohol Consumption ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Legal Status ◽  
Current Knowledge ◽  
Uterine Fibroids ◽  
Future Directions ◽  
Working Adults ◽  
The Us ◽  
Alcohol Related Problems

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well.

Current Status of Knowledge and Awareness of Diabetes Mellitus in Saudi Arabia

2020 ◽  
Vol 16 ◽  
Author(s):  
Asirvatham Alwin Robert ◽  
Ahmad Dakeel Al Awad ◽  
Mohamed Abdulaziz Al Dawish
Keyword(s):  
Diabetes Mellitus ◽  
Saudi Arabia ◽  
Disease Risk ◽  
Current Knowledge ◽  
Adult Population ◽  
Management Training ◽  
Control Measures ◽  
Current Status ◽  
Treatment Modalities ◽  
The Government

Abstract: Diabetes mellitus (DM) is a chronic disease, and the complications may be life-threatening; however, with proper treatment and control measures, it can be very well-managed. Self-management training and education of diabetes are critical in diabetes care and management. It is essential that patients with diabetes must have a comprehensive understanding of the nature of the disease, risk factors, complications, and possible treatment modalities to attenuate the complications. Over the last few years, DM in Saudi Arabia has been rapidly growing at an alarming rate. It has affected around one-fifth of the adult population, and by 2030, the numbers are predicted to rise further and exceed more than double the present number. An estimated tenfold increase has been reported over the past three decades in Saudi Arabia. However, there has not been much research focusing on understanding the knowledge and awareness of DM in Saudi Arabia as compared to developed nations. This review aims to present an overview of the current knowledge and awareness level of DM among the population of Saudi Arabia through an extensive review of the currently available literature. The review findings could be of immense assistance to the government, healthcare systems, educational institutions, and researchers to develop evidence-based programs, policies, and guidelines towards increasing the knowledge and awareness about diabetes and its management, so that early detection and management can be ensured to control the escalating burden of diabetes, in Saudi Arabia.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

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