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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Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice

Environment International, Год журнала: 2023, Номер 172, С. 107769 - 107769

Опубликована: Янв. 23, 2023

Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure cardiometabolic mortality in humans, societal costs ∼ $39 billion/year or more. We recently demonstrated that several widely used EDCs increase disease appropriate mouse models. In addition affecting adult health, parental has also been shown cause metabolic disorders, including obesity and diabetes, offspring. While most studies have focused on impact maternal EDC offspring's little known about effects paternal exposure. current study, we investigated adverse a but understudied phthalate, dicyclohexyl (DCHP) health F1 F2 offspring mice. Paternal DCHP led exacerbated insulin resistance impaired signaling without diet-induced obesity. previously showed sperm small non-coding RNAs tRNA-derived (tsRNAs) rRNA-derived (rsRNAs) contribute intergenerational transmission paternally acquired disorders. Using novel PANDORA-seq, revealed can lead tsRNA/rsRNA landscape changes were undetected by traditional RNA-seq, which may DCHP-elicited effects. Lastly, found sex-specific transgenerational elicited glucose intolerance female descendants. Our results suggest phthalates their These findings our understanding etiology human diseases originating from chemical-elicited

Язык: Английский

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Microplastics exposure: implications for human fertility, pregnancy and child health

Frontiers in Endocrinology, Год журнала: 2024, Номер 14

Опубликована: Янв. 4, 2024

Plastics found in our everyday environment are becoming an increasing concern for individual and population-level health, the extent of exposure potential toxic effects these contaminants on numerous human organ systems clear. Microplastics (MPs), tiny plastic particles, appear to have many same biological as their precursors compounded effect accumulation different organs. Recently, microplastic was observed placenta, raising important questions related health pregnancies offspring. These concerns particularly heightened considering developmental origins disease (DOHaD) framework, which postulates that utero can programme lifelong The current review examines state knowledge this topic highlights avenues future investigation.

Язык: Английский

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How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health

Clinical Epigenetics, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 16, 2025

Recent studies support the influence of paternal lifestyle and diet before conception on health offspring via epigenetic inheritance through sperm DNA methylation, histone modification, small non-coding RNA (sncRNA) expression regulation. Smoking may induce hypermethylation in genes related to anti-oxidation insulin resistance. Paternal obesity are associated with greater risks metabolic dysfunction alterations sperm. Metabolic changes, such as high blood glucose levels increased body weight, commonly observed fathers subjected chronic stress, addition an enhanced risk depressive-like behaviour sensitivity stress both F0 F1 generations. methylation is correlated quality ability fertilise oocytes, possibly a differentially regulated MAKP81IP3 signalling pathway. exposure toxic endocrine-disrupting chemicals (EDCs) also linked transgenerational transmission predisposition disease, infertility, testicular disorders, obesity, polycystic ovarian syndrome (PCOS) females changes during gametogenesis. As success assisted reproductive technology (ART) affected by diet, BMI, alcohol consumption, its outcomes could be improved modifying factors that dependent male choices environmental factors. This review discusses importance signatures sperm—including retention, sncRNA—for functionality, early embryo development, health. We discuss mechanisms which (obesity, smoking, EDCs, stress) impact epigenome.

Язык: Английский

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Impact of Endocrine Disruptors upon Non-Genetic Inheritance

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(6), С. 3350 - 3350

Опубликована: Март 20, 2022

Similar to environmental factors, EDCs (endocrine-disrupting chemicals) can influence gene expression without modifying the DNA sequence. It is commonly accepted that transgenerational inheritance of parentally acquired traits conveyed by epigenetic alterations also known as "epimutations". methylation, acetylation, histone modification, RNA-mediated effects and extracellular vesicle are mechanisms have been described so far be responsible for these epimutations. They may lead diverse phenotypes in progeny when they occur germ cells an affected individual. While EDC-induced health dramatically increased over past decade, limited on sperm epigenetics described. However, there has a gain interest this issue recent years. The gametes (sperm oocyte) represent targets thus route environmentally induced changes several generations. This review aims at providing overview might implicated inheritance.

Язык: Английский

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Mixtures of per- and polyfluoroalkyl substances (PFAS) alter sperm methylation and long-term reprogramming of offspring liver and fat transcriptome

Environment International, Год журнала: 2024, Номер 186, С. 108577 - 108577

Опубликована: Март 16, 2024

Male fertility has been declining worldwide especially in countries with high levels of endocrine disrupting chemicals (EDCs). Per- and polyfluorinated alkyl Substances (PFAS) have classified as EDCs linked to adverse male reproductive health. The mechanisms these associations their implications on offspring health remain unknown. aims the current study were assess effect PFAS mixtures sperm methylome transcriptional changes metabolic tissues (i.e., liver fat). C57BL/6 mice exposed a mixture (PFOS, PFOA, PFNA, PFHxS, Genx; 20 µg/L each) for 18-weeks or water control. Genome-wide methylation was assessed F0 epidydimal using reduced representation bisulfite sequencing (RRBS) Illumina mouse array, while gene expression by bulk RNA 8-week-old derived from unexposed females. resulted 2,861 83 (Illumina) DMRs (q < 0.05). Functional enrichment revealed that PFAS-induced associated behavior developmental pathways RRBS, related lipid metabolism cell signaling. Additionally, 40 53 differentially expressed genes (DEGs) fat males, 9 31 DEGs females, respectively. alterations cholesterol mitotic cycle regulation myeloid leukocyte migration offspring, female erythrocyte development carbohydrate catabolism affected fat. Our results demonstrate exposure legacy newly emerging adult result aberrant altered sex-specific manner. These data indicate preconception males can be transmitted affect phenotype next generation.

Язык: Английский

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The Association between Long-Term DDT or DDE Exposures and an Altered Sperm Epigenome—a Cross-Sectional Study of Greenlandic Inuit and South African VhaVenda Men

Environmental Health Perspectives, Год журнала: 2024, Номер 132(1)

Опубликована: Янв. 1, 2024

The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT applied, well the Arctic, endocrine disrupting metabolite, p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) accumulates marine mammals and fish. p,p′-DDE exposures are linked birth defects, infertility, cancer, neurodevelopmental delays. Of particular concern potential of use impact generations come via heritable sperm epigenome.

Язык: Английский

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Lifestyle interventions to reduce endocrine-disrupting phthalate and phenol exposures among reproductive age men and women: A review and future steps

Environment International, Год журнала: 2022, Номер 170, С. 107576 - 107576

Опубликована: Окт. 14, 2022

Non-persistent endocrine-disrupting chemicals (EDCs), including phthalates and phenols, are ubiquitous in both the environment human body. A growing body of epidemiologic studies have identified concerning links between EDCs adverse reproductive developmental health effects. Despite consistent evidence, risk assessments policy interventions often arrive late. This presents an urgent need to identify evidence-based for implementation at clinical community levels reduce EDC exposure, especially susceptible populations. The life cycle (menarche menopause females after pubertal onset males) includes some most vulnerable periods environmental exposures, such as preconception perinatal stages, representing a key window opportunity intervene prevent unfavorable outcomes. review aims synthesize assess behavioral, dietary, residential EDC-driven develop recommendations subsequent, larger-scale that address knowledge-gaps current during cycle. We selected 21 primary evaluation, addition four supplemental interventions. Among these, accessible (web-based) educational resources, targeted replacement (known) toxic products, personalization intervention through meetings support groups, were promising strategies reducing concentrations. However, we document paucity phthalate phenol exposures years, among men. Accordingly, recommend additional, larger community-based exposure. Specifically, future should focus on short-term, mid-, long-term exposure reduction phenols. latter, especially, is required development public guidelines promote globally.

Язык: Английский

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Di-2-ethylhexyl phthalate (DEHP) exposure induces sperm quality and functional defects in mice

Chemosphere, Год журнала: 2022, Номер 312, С. 137216 - 137216

Опубликована: Ноя. 9, 2022

Язык: Английский

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Mechanistic target of rapamycin (mTOR) pathway in Sertoli cells regulates age-dependent changes in sperm DNA methylation

eLife, Год журнала: 2024, Номер 13

Опубликована: Янв. 3, 2024

Over the past several decades, a trend toward delayed childbirth has led to increases in parental age at time of conception. Sperm epigenome undergoes age-dependent changes increasing risks adverse conditions offspring conceived by fathers advanced age. The mechanism(s) linking paternal with epigenetic sperm remain unknown. is shaped compartment protected blood-testes barrier (BTB) known deteriorate Permeability BTB regulated balance two mTOR complexes Sertoli cells where complex 1 (mTORC1) promotes opening and 2 (mTORC2) its integrity. We hypothesized that this also responsible for epigenome. To test hypothesis, we analyzed reproductive outcomes, including DNA methylation transgenic mice cell-specific suppression mTORC1 ( Rptor KO) or mTORC2 Rictor KO). accelerated aging methylome resulted phenotype concordant older age, decreased testes weight counts, increased percent morphologically abnormal spermatozoa mitochondrial copy number. Suppression shift opposite associated physiological – rejuvenation mild parameters. These results demonstrate first regulates rate aging. Thus, pathway may be used as novel target therapeutic interventions rejuvenate advanced-age fathers.

Язык: Английский

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