Search Results (103)

Poly- and perfluorinated alkyl substances (PFAS) are a group of chemicals that are widely used, prevalent in the environment, associated with several toxic effects, and often have long half-lives. Their persistence and relevant toxicity are the primary causes of environmental and human health concerns, and they are referred to as “forever chemicals” because of their persistence. Environmental accumulation caused by slow natural biodegradation and subsequent long environmental half-lives leads to bioaccumulation and makes PFAS more likely to be chronically toxic with potential transgenerational effects. Ultimately, it is this persistence that causes the greatest concern because PFAS-contaminated sites need costly remediation techniques, or else the contaminated areas will not be available for proper economic development because of social and economic suppression. Non-PFAS, alternative Aqueous Film Forming Foams (AFFF) that are considered environmentally friendly, are being heavily considered or currently used for fire suppression instead of PFAS-based products. The bioaccumulation and toxicity of alternative AFFF are just starting to be studied. The purpose of this review is to discuss the basic environmental and human health effects of PFAS and alternative AFFF that propel regulatory changes, increase clean-up costs, reduce economic development, and drive the development of novel alternatives. Full article

Background/Objectives: Overnutrition increases comorbidities such as gestational diabetes during pregnancy that can have detrimental consequences for both parent and progeny. We previously reported that high-fat (HF) diet and late-gestation diabetes (DM) incite mitochondrial dysfunction, oxidative stress, and cardiometabolic disease in first generation (F1) rat offspring, partially through epigenomic and transcriptomic programming. Primordial germ cells, which become the second generation (F2), are also exposed, which could incite generational risk. This study aimed to determine whether the F2 transcriptome already has genomic variation at the preimplantation embryo stage, and whether variations normalize, persist or compound in the third generation (F3). Methods: F0 female rats were fed a control or HF diet, then DM was induced in HF-fed dams on gestational day (GD)14, exposing F1 offspring and F2 primordial germ cells to hyperlipidemia, hyperglycemia and fetal hyperinsulinemia during the last third of pregnancy. F1 pups were reared by healthy dams and bred to produce F2 embryos (F2e) and F2 pups. F2 offspring were bred to produce F3 embryos (F3e). Embryos were assessed by a novel grading method, live cell imaging, and single-cell RNA sequencing. Results: Embryo grades were not different, but HF+DM F2e had more cells while F3e had fewer cells and overall fewer embryos. HF+DM F2e had similar mitochondria quantity but a downregulation of genes involved in lipid metabolism and more oxidative stress, consistent with mitochondrial dysfunction. They also had an upregulation of chromatin-remodeling genes. The predicted developmental effect is accelerated embryo aging and epigenetic drift. In contrast, HF+DM F3e had an adaptive stress response leading to increased mitochondria quantity and an upregulation of genes involved in mitochondrial respiration, metabolism, and genomic repair that led to a predicted developmental effect of delayed embryo maturation. Conclusions: Although pathways vary, both generations have metabolically linked differentially expressed genes that influence cell fate and developmental pathways. In conclusion, HF+DM pregnancy can program the early embryonic transcriptome for three generations, despite an intergenerational healthy diet. Full article

Heavy metal contamination in freshwater ecosystems poses persistent threats to aquatic organisms and public health. This study evaluates the transgenerational toxicity of cadmium chloride and copper sulfate on Culex pipiens, focusing on development, reproduction, and midgut histopathology over two successive generations. Larval bioassays showed cadmium chloride to be more toxic than copper sulfate, with early instars exhibiting higher sensitivity (LC₅₀ = 8.66 μg/L for Cd; 175.63 μg/L for Cu). Both metals significantly delayed larval and pupal development, reduced fecundity, and decreased egg hatchability in a dose-dependent manner. Histopathological examination revealed midgut epithelial degeneration, vacuolation, and brush border loss, with copper sulfate inducing more severe cytotoxicity. These findings confirm that sublethal, chronic metal exposure can impair physiological and reproductive traits across generations. Moreover, this study highlights the utility of mosquitoes as sensitive bioindicators of aquatic pollution, and underscores the long-term ecological implications of heavy metal contamination on vector dynamics and disease transmission. Full article

The epigenetic landscape plays a pivotal role in regulating the functions of both germ and somatic cells (Sertoli and Leydig cells) within the testis, which are essential for male fertility. While somatic cells support germ cell maturation and testosterone synthesis, the epigenetic regulation of germ cells is critical for proper spermatogenesis and function. Epigenetic modifications such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs (ncRNAs) are crucial for regulating gene expression that is essential for spermatogenesis and reproductive function. Although numerous studies have highlighted the significance of the epigenome and its implications for male reproductive health, a comprehensive overview of the existing literature and knowledge is lacking. This review aims to provide an in-depth analysis of the role of epigenetics in spermatogenesis and reproductive health, with a specific focus on DNA methylation, histone remodeling, and small noncoding RNAs (sncRNAs). Additionally, we examine the impact of lifestyle and environmental factors, such as diet, smoking, physical activity, and exposure to endocrine-disrupting chemicals, on the sperm epigenome. We emphasize how these factors influence fertility, embryonic development, and potential transgenerational inheritance. This review underscores how recent advances in the understanding of the epigenetic modulation of testicular function can inform the pathophysiology of male infertility, thereby paving the way for the development of targeted diagnostic and therapeutic strategies. Full article

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article

Per- and polyfluoroalkyl substances (PFASs) comprise a diverse array of synthetic chemicals that resist environmental degradation. They are increasingly recognised as endocrine-disrupting compounds (EDCs). These chemicals, found in non-stick cookware, food packaging, and industrial waste, accumulate in human tissues and fluids, raising substantial concerns regarding their impact on female reproductive health. Epidemiological studies have demonstrated associations between PFAS exposure and reduced fertility; nevertheless, the underlying molecular pathways remain inadequately understood. This narrative review investigates the multifaceted effects of PFASs on ovarian physiology, including its disruption of the hypothalamic–pituitary–ovarian (HPO) axis, alteration of anti-Müllerian hormone (AMH) levels, folliculogenesis, and gonadotropin receptor signalling. Significant attention is directed towards the emerging association between PFASs and polycystic ovarian syndrome (PCOS), wherein PFAS-induced hormonal disruption may exacerbate metabolic issues and elevated androgen levels. Furthermore, we analyse the current data regarding PFAS exposure in women undergoing treatment based on assisted reproductive technologies (ARTs), specifically in vitro fertilisation (IVF), highlighting possible associations with diminished oocyte quality, suboptimal embryo development, and implantation failure. We examine potential epigenetic and transgenerational alterations that may influence women’s reproductive capabilities over time. This study underscores the urgent need for further research and regulatory actions to tackle PFAS-related reproductive toxicity, particularly in vulnerable populations, such as women of reproductive age and those receiving fertility treatments. Full article

Male reproductive aging proceeds gradually and involves complex alterations across germ cells, somatic cells, and the testicular niche. Multi-omics analyses highlight shifts in spermatogonial stem cell dynamics, diminished sperm quantity and quality, and reconfigured support from Sertoli and Leydig cells. These somatic cells show numerical declines and exhibit senescence-associated changes that amplify inflammatory signals and compromise blood–testis barrier integrity. Concurrently, fibrosis and heightened immune cell infiltration disrupt intercellular communication, contributing to further deterioration of spermatogenesis. Epigenetic remodeling—including DNA methylation drift, histone modification imbalances, and altered small non-coding RNA profiles—adds another dimension, reducing sperm integrity and potentially exerting transgenerational effects on offspring health. Observed hormonal changes, such as reduced testosterone and INSL3 production by aging Leydig cells, reflect the additional weakening of testicular function. These multifactorial processes collectively underlie the drop in male fertility and the increased incidence of adverse outcomes, such as miscarriages and developmental anomalies in the offspring of older fathers. Research into mitigation strategies, including interventions targeting senescent cells, oxidative stress, and inflammatory pathways, may slow or reverse key mechanisms of testicular aging. These findings underscore the importance of understanding the molecular hallmarks of male reproductive aging for preserving fertility and safeguarding offspring well-being. Full article

Intimate partner violence (IPV) is the main cause of violence against women, especially in Mexico. However, the causes, consequences, and solutions related to IPV have not been well understood in this population. A total of five focus groups that included Mexican women who were victims of IPV were conducted to understand the causes, consequences, and solutions related to IPV, and a thematic analysis was performed. A total of 32 participants were included, with a median (range) age of 35 (24–70). The main causes mentioned by the participants were (a) cultural ones, among which Machismo, transgenerational violence, and cultural norms and gender roles were the main categories; (b) emotional causes, among which the lack of emotional abilities and emotional dependence were the main categories; and (c) educative causes, among which the lack of information about mental health, emotional abilities, IPV, and healthy relationships was reported. The main consequences mentioned were (a) psychological; (b) physical; (c) economic; (d) family-related, including impacts on children; and (e) legal, in relation to IPV complaints and children’s custody. Finally, the main solutions mentioned by the participants were (a) prevention through education, including educational programs to address mental health, IPV information, healthy relationships, and training in emotional skills; (b) cultural transformation; and (c) institutional strengthening, with this last solution including improving public policies, improving legal advice, and training for legal authorities. In conclusion, the causes, consequences, and solutions related to IPV were varied and included many instances; therefore, its prevention and solution should be performed at the inter-institutional and community levels, in which the promotion of emotional skills should play a fundamental role. Full article

Male-factor infertility accounts for nearly half of all infertility cases, and mounting evidence points to oxidative stress as a pivotal driver of sperm dysfunction, genetic instability, and epigenetic dysregulation. In particular, the oxidative DNA lesion 8-hydroxy-2′-deoxyguanosine (8-OHdG) has emerged as a central mediator at the interface of DNA damage and epigenetic regulation. We discuss how this lesion can disrupt key epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNAs, thereby influencing fertilization outcomes, embryo development, and offspring health. We propose that the interplay between oxidative DNA damage and epigenetic reprogramming is further exacerbated by aging in both the paternal and maternal germlines, creating a “perfect storm” that increases the risk of heritable (epi)mutations. The consequences of unresolved oxidative lesions can thus persist beyond fertilization, contributing to transgenerational health risks. Finally, we explore the promise and potential pitfalls of antioxidant therapy as a strategy to mitigate sperm oxidative damage. While antioxidant supplementation may hold significant therapeutic value for men with subfertility experiencing elevated oxidative stress, a careful, personalized approach is essential to avoid reductive stress and unintended epigenetic disruptions. Recognizing the dual role of oxidative stress in shaping both the genome and the epigenome underscores the need for integrating redox biology into reproductive medicine, with the aim of improving fertility treatments and safeguarding the health of future generations. Full article

The endocannabinoid system (ECS) is a complex endocrine network involved in maintaining body homeostasis. It comprises endocannabinoids, their receptors (CB1 and CB2), and the enzymes and transporters responsible for their synthesis and degradation. While the ECS’s role in the nervous system is well established, its functions in other organs and peripheral tissues, including the cardiovascular, gastrointestinal, and reproductive systems, remain incompletely understood. With the increasing use of marijuana, particularly among individuals of reproductive age, concerns have emerged regarding its potential impact on male and female fertility. Phytocannabinoids (∆9tethrahydrocannabinol and cannabidiol), as well as synthetic cannabimimetic drugs, interact with the ECS, influencing sperm and oocyte physiology and reproductive outcomes. Recent research has identified ECS-related biomarkers with potential applications in infertility diagnosis, particularly in assessing male fertility with greater precision. Furthermore, emerging evidence suggests that ECS signaling pathways are involved in epigenetic modifications, which may influence health maintenance, disease susceptibility, and transgenerational inheritance patterns. These findings highlight the therapeutic potential of ECS modulation in reproductive disorders and broader medical applications. This narrative review aims to elucidate the role of the ECS in human reproduction, with a particular focus on the influence of endocannabinoids on gametogenesis. While current research underscores the critical role of the ECS in fertility, further investigations are needed to fully elucidate its underlying mechanisms and its broader implications for reproductive health and therapeutic interventions. Full article

Trauma can impact individuals within a generation (intragenerational) and future generations (transgenerational) through a complex interplay of biological and environmental factors. This review explores the epigenetic mechanisms that have been correlated with the effects of trauma across generations, including DNA methylation, histone modifications, and non-coding RNAs. These mechanisms can regulate the expression of stress-related genes (such as the glucocorticoid receptor (NR3C1) and FK506 binding protein 5 (FKBP5) gene), linking trauma to biological pathways that may affect long-term stress regulation and health outcomes. Although research using model organisms has elucidated potential epigenetic mechanisms underlying the intergenerational effects of trauma, applying these findings to human populations remains challenging due to confounding variables, methodological limitations, and ethical considerations. This complexity is compounded by difficulties in establishing causality and in disentangling epigenetic influences from shared environmental factors. Emerging therapies, such as psychedelic-assisted treatments and mind–body interventions, offer promising avenues to address both the psychological and potential epigenetic aspects of trauma. However, translating these findings into effective interventions will require interdisciplinary methods and culturally sensitive approaches. Enriched environments, cultural reconnection, and psychosocial interventions have shown the potential to mitigate trauma’s impacts within and across generations. By integrating biological, social, and cultural perspectives, this review highlights the critical importance of interdisciplinary frameworks in breaking cycles of trauma, fostering resilience, and advancing comprehensive healing across generations. Full article

Low-dose ionizing radiation (LDIR) is a prevalent environmental factor with profound impacts on male reproductive health, particularly on the testicular immune microenvironment. This review examines the multifaceted effects of LDIR, emphasizing its ability to induce genotoxic stress, oxidative damage, and epigenetic modifications in reproductive cells. These alterations compromise DNA repair, disrupt chromatin structure, and induce immune dysregulation. Immune cells such as macrophages, T cells, natural killer cells, and dendritic cells exhibit significant functional changes under LDIR exposure, destabilizing the immune privilege critical for normal spermatogenesis. The long-term health implications of LDIR include impaired sperm quality, reduced fertility, and transgenerational risks through heritable genomic instability. This review underscores the importance of exploring the mechanisms underlying immune dysregulation and developing effective protective strategies. While LDIR’s full impact on male reproductive health remains to be elucidated, addressing the gaps in our understanding of immune microenvironmental changes is crucial for mitigating its adverse effects and improving reproductive health outcomes. Full article

We are exposed to a variety of environmental chemicals in our daily lives. It is possible that the effects of this daily chemical exposure could accumulate in the organism in some form and influence health and disease development. The exposure effects extend throughout the human lifetime, not only after birth, but also during the embryonic period. Epigenetics is an important target for the molecular mechanisms of daily environmental chemical effects. Epigenetics is a mechanism of gene transcription regulation that does not involve changes in DNA sequence. The Developmental Origins of Health and Disease (DOHaD) theory has also been proposed, in which effects such as exposure to environmental chemicals during embryonic period are mediated by epigenetic changes, which may lead to risk for disease development and adverse health effects after maturity. This review summarizes the association between embryonic exposure and the epigenetics of well-known non-essential toxic heavy metals (methylmercury, cadmium, arsenic, and lead), a representative group of environmental chemicals. In the future, it will be important to predict the epigenetic mechanisms of unknown chemical and combined exposures. In addition, further experimental investigations using experimental animals and the accumulation of knowledge are needed to study the transgenerational effects of environmental chemicals in the future. Full article

Nanoplastics (NPs) represent a major challenge in environmental contamination resulting from the physical, chemical, and biological degradation of plastics. Their characterization requires advanced and expensive methods, which limit routine analyses. The biological effects of NPs depend on their chemical and physical properties, which influence toxicity and interactions with biological systems. Studies in animal models, such as Daphnia magna and Danio rerio, show that NPs induce oxidative stress, inflammation, DNA damage, and metabolic alterations, often related to charge and particle size. NPs affect endocrine functions by acting as endocrine disruptors, interfering with thyroid and sex hormones and showing potential transgenerational effects through epigenetic modifications, including DNA hyper- and hypomethylation. Behavioral and neurofunctional alterations have been observed in Danio rerio and mouse models, suggesting a link between NP exposure and neurotransmitters such as dopamine and serotonin. Despite limited human studies, the presence of NPs in breast milk and placenta underscores the need for further investigation of health effects. Research focusing on genetic and epigenetic markers is encouraged to elucidate the molecular mechanisms and potential risks associated with chronic exposure. Full article

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, and non-coding RNA activity—are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these processes, leading to impaired sperm function and male infertility. This disruption extends to epigenetic modifications, resulting in abnormal gene expression and chromatin remodeling that compromise genomic integrity and fertilization potential. Importantly, oxidative-stress-induced epigenetic alterations can be inherited, affecting the health and fertility of offspring and future generations. This review investigates how oxidative stress influences epigenetic regulation in male reproduction by modifying DNA methylation, histone modifications, and non-coding RNAs, ultimately compromising spermatogenesis. Additionally, it discusses the transgenerational implications of these epigenetic disruptions and their potential role in hereditary infertility and disease predisposition. Understanding these mechanisms is vital for developing therapeutic strategies that mitigate oxidative damage and restore epigenetic homeostasis in the male germline. By integrating insights from molecular, clinical, and transgenerational research, this work emphasizes the need for targeted interventions to enhance male reproductive health and prevent adverse outcomes in progeny. Furthermore, elucidating the dose–response relationships between oxidative stress and epigenetic changes remains a critical research priority, informing personalized diagnostics and therapeutic interventions. In this context, future studies should adopt standardized markers of oxidative damage, robust clinical trials, and multi-omic approaches to capture the complexity of epigenetic regulation in spermatogenesis. Such rigorous investigations will ultimately reduce the risk of transgenerational disorders and optimize reproductive health outcomes. Full article