DNA methylation in mammalian development and disease

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 12, 2024

The DNA methylation field has matured from a phase of discovery and genomic characterization to one seeking deeper functional understanding how this modification contributes development, ageing disease. In particular, the past decade seen many exciting mechanistic discoveries that have substantially expanded our appreciation for generic, evolutionarily ancient can be incorporated into robust epigenetic codes. Here, we summarize current distinct landscapes emerge over mammalian lifespan discuss they interact with other regulatory layers support diverse functions. We then review rising interest in alternative patterns found during senescence somatic transition cancer. Alongside advancements single-cell long-read sequencing technologies, collective insights made across these fields offer new opportunities connect biochemical genetic features cell physiology, developmental potential phenotype. Review, Smith et al. describe development within key disease states, as well different methyltransferases interface histone modifications proteins create maintain them.

Language: Английский

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Frequency, morbidity and equity — the case for increased research on male fertility

Nature Reviews Urology, Journal Year: 2023, Volume and Issue: 21(2), P. 102 - 124

Published: Oct. 12, 2023

Language: Английский

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The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1459 - 1459

Published: Jan. 25, 2024

Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, zygotic genome undergoes maternal-to-zygotic transition (MZT) subsequent activation (ZGA), marking initiation transcriptional control gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity many mammals. Recent advances chromatin analysis have enabled detailed explorations histone during ZGA. This review delves into conserved unique regulatory strategies, providing essential insights dynamic changes their variants ZGA The objective is to explore recent advancements leading mechanisms related governing embryonic development phase depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation diverse biological contexts. It also contribute extensive areas evolutionary developmental biology possibly lay foundation research discussion on seminal topic.

Language: Английский

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Adverse effects of bisphenol A and its analogues on male fertility: An epigenetic perspective

Environmental Pollution, Journal Year: 2024, Volume and Issue: 345, P. 123393 - 123393

Published: Jan. 22, 2024

Language: Английский

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Current global status of male reproductive health

Human Reproduction Open, Journal Year: 2024, Volume and Issue: 2024(2)

Published: Jan. 1, 2024

Abstract BACKGROUND The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline sperm counts, has intensified concerns about status of MRH. Consequently, there is a pressing requirement for strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data develop evidence-based strategies. methods addressing questions pathways toward their answers will inevitably vary based on variations cultural, geopolitical, health-related contexts. To address issues, conjoint ESHRE Male Reproductive Health Initiative (MRHI) Campus workshop was convened. OBJECTIVE AND RATIONALE three objectives were: first, assess current state MRH around world; second, identify some key gaps knowledge; and, third, examine how stakeholders can collaboratively generate intelligent effective paths forward. SEARCH METHODS Each expert reviewed summarized literature that subsequently used provide comprehensive overview challenges related OUTCOMES This narrative report an data, opinions, arguments presented during workshop. A number outcomes are be following overarching themes: serious issue plethora our understanding; need international collaborative networks undertake multidisciplinary research into fundamental lifestyle/environmental exposure studies, high-quality clinical trials; urgent strategies educate young people general public safeguard improve across diverse population demographics resources. LIMITATIONS, REASONS FOR CAUTION where worldwide leading experts from wide range disciplines discussed evidence regarding While each placed it context, areas limited and/or sparse. Equally, important consideration may have been missed. Moreover, clear knowledge base, which makes conclusions necessarily speculative warranting further study. WIDER IMPLICATIONS Poor suffers low awareness among public, patients, heathcare professionals. Addressing this require coordinated approach. significant policy makers prioritizing its funding. STUDY FUNDING/COMPETING INTEREST(S) authors would like extend gratitude providing financial support Budapest Workshop, well Microptic S.L. (Barcelona) kindly sponsoring P.B. Director not-for-profit organization Global Action Men’s receives fees expenses his work, (which includes preparation manuscript). Conflicts interest: C.J.D.J., C.L.R.B., R.A.A., P.B., M.P.C., M.L.E., N.G., N.J., C.K., AAP, M.K.O., S.R.-H., M.H.V.-L.: Workshop 2022 (Travel support—personal). C.J.D.J.: Cambridge University Press (book royalties—personal). Annual Meeting Yale Panel 2023 C.L.R.B.: Ferring IBSA (Lecture), RBMO editor (Honorarium travel, etc.), ExSeed ExScentia (University Dundee), Bill & Melinda Gates Foundation (for contraception). M.P.C.: Previously received funding pharmaceutical companies economic research. not relation work had no bearing contents work. No other sources provided (funding company Market Access Solutions). M.L.E.: Advisor Ro, Doveras, Next, Hannah, Sandstone. C.K.: European Academy Andrology (Past president UNPAID), S.K.: CEO His Turn, fertility Diagnostic Therapeutic (No payments or profits date). R.I.M.: www.healthymale.org.au (Australian Government funded profit men’s sector (Employed Medical 0.2 FET), Monash IVF Pty Ltd (Equity holder)). N.J.: Merck (consulting fees), Gedeon Richter (honoraria). S.R.-H.: reimbursements). C.N.: LLC (Nursing educator); COMMIT (Core Outcomes Measures Infertility Trials) Advisor, meeting attendee, co-author; COMMA Menopause) International Federation Gynecology Obstetrics (FIGO) Delegate Letters Sciences; ReproNovo, Advisory board; American Board Urology Examiner; Urological Association Journal subsection editor, committee member, guidelines co-author Scientific trial NexHand Chief Technology Officer, stock ownership Posterity ownership. A.P.: Economic Social Research Council (A collaborator grant ES/W001381/1). Member advisory Serono (November 2022), board Exceed Health, Speaker educational events organized Mealis Group; Chairman Cryos External Committee: All associated with paid former employer Sheffield. Trustee Progress Educational Trust (Unpaid). M.K.O.: National Australian (Funding topic fertility), aimed at development gamete-based contraception), Future Fund defining long-term consequences infertility). Department Sexual (SRH)/Human Reproduction Programme (HRP) Project RP2/WHO Review Member; MRHI Group Member), (member), EGOI (Member); Human (Associate Editor), Fertility Sterility (Editor), AndroLATAM (Founder Coordinator).

Language: Английский

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Early Life Stress and Major Depressive Disorder—An Update on Molecular Mechanisms and Synaptic Impairments

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 6469 - 6483

Published: Feb. 3, 2024

Language: Английский

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Contribution of the seminal microbiome to paternal programming

Biology of Reproduction, Journal Year: 2024, Volume and Issue: 111(2), P. 242 - 268

Published: May 2, 2024

Abstract The field of Developmental Origins Health and Disease has primarily focused on maternal programming offspring health. However, emerging evidence suggests that paternal factors, including the seminal microbiome, could potentially play important roles in shaping developmental trajectory long-term health outcomes. Historically, microbes present semen were regarded as inherently pathogenic agents. this dogma recently been challenged by discovery a diverse commensal microbial community within healthy males. In addition, recent studies suggest transmission semen-associated into female reproductive tract during mating potentials to not only influence fertility embryo development but also contribute offspring. review, we summarize current knowledge microbiota both humans animals followed discussing their potential involvement We propose discuss mechanisms through which influences are transmitted via microbiome. Overall, review provides insights microbiome-based programing, will expand our understanding currently epigenetic modifications, oxidative stresses, cytokines.

Language: Английский

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Acquired sperm hypomethylation by gestational arsenic exposure is re-established in both the paternal and maternal genomes of post-epigenetic reprogramming embryos

Epigenetics & Chromatin, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 16, 2025

DNA methylation plays a crucial role in mammalian development. While methylome changes acquired the parental genomes are believed to be erased by epigenetic reprogramming, accumulating evidence suggests that sperm caused environmental factors involved disease phenotypes of offspring. These findings imply transferred embryo after reprogramming. However, our understanding this process remains incomplete. Our previous study showed arsenic exposure F0 pregnant mice paternally increased tumor incidence F2 The arsenic-exposed F1 males exhibited characteristic features, including enrichment hypomethylated cytosines at promoters retrotransposons LINEs and LTRs. Hypomethylation is potentially detrimental. Determining whether these hypomethylation important confirming molecular pathway intergenerational transmission paternal effects exposure. We investigated male embryos reprogramming reduced representation bisulfite sequencing (RRBS) allele-specific analysis. To do so, were obtained crossing control or gestationally (C3H/HeN strain) with females (C57BL/6 strain). results revealed group was globally enriched for certain genomic regions, LTR LINE, as observed group. Unexpectedly, features detected not only genome but also maternal embryos. Furthermore, found rarely occur same positions between characteristics arsenic-induced reproduced both post-epigenetic suggest re-establishment achieved collaboration other mediate region-specific changes. highlight possibility could contribute development predisposition

Language: Английский

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

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 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.

Language: Английский

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Paternal effects on fetal programming

Animal Reproduction, Journal Year: 2023, Volume and Issue: 20(2)

Published: Jan. 1, 2023

Paternal programming is the concept that environmental signals from sire's experiences leading up to mating can alter semen and ultimately affect phenotype of resulting offspring. Potential mechanisms carrying paternal effects offspring be associated with epigenetic signatures (DNA methylation, histone modification non-coding RNAs), oxidative stress, cytokines, seminal microbiome. Several opportunities exist for sperm/semen influenced during development; these are within testicle, epididymis, or accessory sex glands. Epigenetic sperm impacted pre-natal pre-pubertal periods, sexual maturity advancing sire age. Sperm susceptible alterations as dictated by their developmental stage at time perturbation, plasma likely have both dependent independent on Research using rodent models has revealed many factors including over/under nutrition, dietary fat, protein, ingredient composition (e.g., macro- micronutrients), exercise, exposure drugs, alcohol, endocrine disruptors all elicit responses evident in phenotype. livestock species also age, fertility level, plane heat stress induce epigenetic, cytokine, microbiome profiles and/or plasma. In addition, recent findings pigs, sheep, cattle indicated blastocysts post-fertilization some continuing into post-natal life Our research group focused understanding common management scenarios nutrition growth rates bulls rams subsequent outcomes. Understanding implication imperative short-term feeding decisions potential impact productivity profitability our herds generations come.

Language: Английский

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