RESUMO

Early-life adversities, whether prenatal or postnatal exposure, have been linked to adverse mental health outcomes later in life increasing the risk of several psychiatric disorders. Research on its neurobiological consequences demonstrated an association between exposure to adversities and persistent alterations in the structure, function, and connectivity of the brain. Consistent evidence supports the idea that regulation of gene expression through epigenetic mechanisms are involved in embedding the impact of early-life experiences in the genome and mediate between social environments and later behavioral phenotypes. In addition, studies from rodent models and humans suggest that these experiences and the acquired risk factors can be transmitted through epigenetic mechanisms to offspring and the following generations potentially contributing to a cycle of disease or disease risk. However, one of the important aspects of epigenetic mechanisms, unlike genetic sequences that are fixed and unchangeable, is that although the epigenetic markings are long-lasting, they are nevertheless potentially reversible. In this review, we summarize our current understanding of the epigenetic mechanisms involved in the mental health consequences derived from early-life exposure to malnutrition, maltreatment and poverty, adversities with huge and pervasive impact on mental health. We also discuss the evidence about transgenerational epigenetic inheritance in mammals and experimental data suggesting that suitable social and pharmacological interventions could reverse adverse epigenetic modifications induced by early-life negative social experiences. In this regard, these studies must be accompanied by efforts to determine the causes that promote these adversities and that result in health inequity in the population.

Assuntos

Epigênese Genética , Transtornos Mentais , Humanos , Animais , Transtornos Mentais/genética , Transtornos Mentais/etiologia , Saúde Mental , Efeitos Tardios da Exposição Pré-Natal/genética , Gravidez , Feminino , Experiências Adversas da Infância , Metilação de DNA

RESUMO

Infantile amnesia, the inability to form long-lasting episodic memories, is a phenomenon extensively known but with no clear understanding of its origins. However, a recent study showed that high rates of hippocampal postnatal neurogenesis degrade episodic-like memories in infants a few days after memory acquisition. Additionally, new studies indicate that exposure to an enriched environment in mice leads to high hippocampal neurogenesis in their offspring. Nevertheless, it is still unclear how this intergenerational trait affects the persistence of hippocampal memories. Therefore, we evaluated spatial memory retention in the offspring of enriched female mice after weaning to address this question. Ten days after spatial learning, we tested memory retention, observing that the offspring of enriched dams increased spatial memory failure; this finding correlates with high proliferation rates in the hippocampus. Furthermore, we evaluated the causal relationship between postnatal hippocampal neurogenesis and memory failure using the antiproliferative drug Temozolomide (TMZ), which rescued spatial memory retrieval. Finally, we evaluated neuronal activity in the hippocampus quantifying the cells expressing the immediate early gene c-Fos. This evaluation showed engram modifications between groups. This neural activity pattern indicates that the high neurogenesis rates can modify memory engrams and cognitive performance. In conclusion, the inherited increase of hippocampal neurogenesis by enriched dams leads to plastic changes that exacerbate infantile amnesia in a spatial task.

RESUMO

Gestational diabetes mellitus (GDM) is a pregnancy complication first detected in the second or third trimester in women that did not show evident glucose intolerance or diabetes before gestation. In 2019, the International Diabetes Federation reported that 15.8% of live births were affected by hyperglycemia during pregnancy, of which 83.6% were due to gestational diabetes mellitus, 8.5% were due to diabetes first detected in pregnancy, and 7.9% were due to diabetes detected before pregnancy. GDM increases the susceptibility to developing chronic diseases for both the mother and the baby later in life. Under GDM conditions, the intrauterine environment becomes hyperglycemic, while also showing high concentrations of fatty acids and proinflammatory cytokines, producing morphological, structural, and molecular modifications in the placenta, affecting its function; these alterations may predispose the baby to disease in adult life. Molecular alterations include epigenetic mechanisms such as DNA and RNA methylation, chromatin remodeling, histone modifications, and expression of noncoding RNAs (ncRNAs). The placenta is a unique organ that originates only in pregnancy, and its main function is communication between the mother and the fetus, ensuring healthy development. Thus, this review provides up-to-date information regarding two of the best-documented (epigenetic) mechanisms (DNA methylation and miRNA expression) altered in the human placenta under GDM conditions, as well as potential implications for the offspring.

RESUMO

Cellular fate and gene expression patterns are modulated by different epigenetic factors including non-coding RNAs (ncRNAs) and chromatin organization. Both factors are dynamic throughout male germ cell differentiation on the seminiferous tubule, despite the transcriptional inactivation in the last stages of spermatogenesis. Sperm maturation during the caput-to-cauda transit on the epididymis involves changes in chromatin organization and the soma-to-germ line transference of ncRNAs that are essential to obtain a functional sperm for fertilization and embryo development. Here, the male environment (diseases, drugs, mental stress) is crucial to modulate these epigenetic factors throughout sperm maturation, affecting the corresponding offspring. Paternal transgenerational inheritance has been directly related to sperm epigenetic changes, most of them associated with variations in the ncRNA content and chromatin marks. Our aim is to give an overview about how epigenetics, focused on ncRNAs and chromatin, is pivotal to understand spermatogenesis and sperm maturation, and how the male environment impacts the sperm epigenome modulating the offspring gene expression pattern.

Assuntos

Cromatina , Epigênese Genética , Diferenciação Celular , Cromatina/genética , Epigênese Genética/genética , Expressão Gênica , Humanos , Masculino , Espermatogênese/genética

RESUMO

A significant number of studies have demonstrated that paternal exercise modulates future generations via effects on the sperm epigenome. However, comprehensive information regarding the effects of exercise performed by the father on different tissues and their clinical relevance has not yet been explored in detail. This narrative review is focused on the effects of paternal exercise training on various physiological systems of offspring. A detailed mechanistic understanding of these effects could provide crucial clues for the exercise physiology field and aid the development of therapeutic approaches to mitigate disorders in future generations. Non-coding RNA and DNA methylation are major routes for transmitting epigenetic information from parents to offspring. Resistance and treadmill exercise are the most frequently used modalities of planned and structured exercise in controlled experiments. Paternal exercise orchestrated protective effects over changes in fetus development and placenta inflammatory status. Moreover paternal exercise promoted modifications in the ncRNA profiles, gene and protein expression in the hippocampus, left ventricle, skeletal muscle, tendon, liver and pancreas in the offspring, while the transgenerational effects are unknown. Paternal exercise demonstrates clinical benefits to the offspring and provides a warning on the harmful effects of a paternal unhealthy lifestyle. Exercise in fathers is presented as one of the most logical and cost-effective ways of restoring health in the offspring and, consequently, modifying the phenotype. It is important to consider that paternal programming might have unique significance in the developmental origins of offspring diseases.

Assuntos

Pai , Condicionamento Físico Animal , Animais , Metilação de DNA , Epigênese Genética , Exercício Físico , Feminino , Humanos , Masculino , Gravidez

RESUMO

Cellular fate and gene expression patterns are modulated by different epigenetic factors including non-coding RNAs (ncRNAs) and chromatin organization. Both factors are dynamic throughout male germ cell differentiation on the seminiferous tubule, despite the transcriptional inactivation in the last stages of spermatogenesis. Sperm maturation during the caput-to-cauda transit on the epididymis involves changes in chromatin organization and the soma-to-germ line transference of ncRNAs that are essential to obtain a functional sperm for fertilization and embryo development. Here, the male environment (diseases, drugs, mental stress) is crucial to modulate these epigenetic factors throughout sperm maturation, affecting the corresponding offspring. Paternal transgenerational inheritance has been directly related to sperm epigenetic changes, most of them associated with variations in the ncRNA content and chromatin marks. Our aim is to give an overview about how epigenetics, focused on ncRNAs and chromatin, is pivotal to understand spermatogenesis and sperm maturation, and how the male environment impacts the sperm epigenome modulating the offspring gene expression pattern.

Assuntos

Humanos , Masculino , Cromatina/genética , Epigênese Genética/genética , Espermatogênese/genética , Expressão Gênica , Diferenciação Celular

RESUMO

Biotic and abiotic stresses alter the pattern of gene expression in plants. Depending on the frequency and duration of stress events, the effects on the transcriptional state of genes are "remembered" temporally or transmitted to daughter cells and, in some instances, even to offspring (transgenerational epigenetic inheritance). This "memory" effect, which can be found even in the absence of the original stress, has an epigenetic basis, through molecular mechanisms that take place at the chromatin and DNA level but do not imply changes in the DNA sequence. Many epigenetic mechanisms have been described and involve covalent modifications on the DNA and histones, such as DNA methylation, histone acetylation and methylation, and RNAi dependent silencing mechanisms. Some of these chromatin modifications need to be stable through cell division in order to be truly epigenetic. During DNA replication, histones are recycled during the formation of the new nucleosomes and this process is tightly regulated. Perturbations to the DNA replication process and/or the recycling of histones lead to epigenetic changes. In this mini-review, we discuss recent evidence aimed at linking DNA replication process to epigenetic inheritance in plants.

RESUMO

This paper presents some of the recent challenges to the Modern Synthesis of evolutionary theory, which has dominated evolutionary thinking for the last sixty years. The focus of the paper is the challenge of soft inheritance - the idea that variations that arise during development can be inherited. There is ample evidence showing that phenotypic variations that are independent of variations in DNA sequence, and targeted DNA changes that are guided by epigenetic control systems, are important sources of hereditary variation, and hence can contribute to evolutionary changes. Furthermore, under certain conditions, the mechanisms underlying epigenetic inheritance can also lead to saltational changes that reorganize the epigenome. These discoveries are clearly incompatible with the tenets of the Modern Synthesis, which denied any significant role for Lamarckian and saltational processes. In view of the data that support soft inheritance, as well as other challenges to the Modern Synthesis, it is concluded that that synthesis no longer offers a satisfactory theoretical framework for evolutionary biology.