'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Thu, 07 Aug 2025 11:52:53 EDT Thu, 07 Aug 2025 11:52:53 EDT jirtle@radonc.duke.edu james001@jirtle.com Personalizing cancer therapy: the role of pharmacogenetics in overcoming drug resistance and toxicity. Nafchi HM, Solatzadeh H, Hajimaghsoudi E, Babakhanzadeh E
Mol Biol Rep (Aug 2025)

Cancer pharmacogenetics has become a cornerstone of precision oncology. It offers the potential to optimize therapeutic outcomes by tailoring treatments to individual genetic profiles. This review explores the central role of pharmacogenomics in addressing key challenges in cancer therapy, including drug resistance, variability in drug response between patients and chemotherapy-induced toxicity. We highlight key pharmacogenetic markers - such as DPYD, TPMT, UGT1A1, CYP2D6, ERCC1 and XRCC1 - that influence the metabolism, efficacy and toxicity of widely used chemotherapeutic agents. In addition, we discuss the role of ATP-binding cassette transporters (ABC transporters), including ABCB1, ABCG2 and ABCC2, in mediating drug resistance and their importance for personalized treatment strategies. Despite significant progress, the clinical translation of pharmacogenomics still faces several challenges. These include the need for large-scale validation of biomarkers in different populations, the integration of gene-environment interactions and the clarification of ethical and privacy concerns related to genetic testing. New technologies such as next-generation sequencing (NGS), liquid biopsies and artificial intelligence (AI)-based predictive models can overcome these obstacles by enabling real-time monitoring of tumor dynamics and refining personalized treatment protocols. The future of cancer pharmacogenetics lies in the integration of multi-omics data encompassing genomics, epigenomics, transcriptomics and proteomics to provide a comprehensive understanding of tumor biology and drug response. Collaboration between academic institutions, pharmaceutical companies and regulatory authorities is essential to establish standardized protocols for biomarker validation and expand pharmacogenomic databases. In addition, the development of ethical frameworks and patient-centered approaches will ensure the responsible integration of pharmacogenomics into clinical practice. By addressing current challenges and utilizing new technologies, cancer pharmacogenetics holds great promise for advancing precision oncology. This review highlights the importance of personalized medicine in improving therapeutic efficacy, minimizing adverse effects and ultimately improving patient outcomes in the fight against cancer.]]> Wed, 31 Dec 1969 19:00:00 EST Molecular aspects of Angelman Syndrome: Defining the new path forward. Almeida JFM, Tonazzini I, Daniele S
Biomol Biomed (Aug 2025)

As a rare neuro-genetic disease, Angelman syndrome (AS) affects about 15 to 500 thousand people worldwide. The AS is an imprinting genomic disease characterized by the loss of function of the maternal UBE3A gene, located in the 15q11-q13. This gene encodes a ~100 kDa protein, the Ubiquitin-protein ligase E3A (UBE3A), that participates in the ubiquitination process, one of the post-translational protein modifications. In the brain, under normal conditions, the paternal allele of the UBE3A gene is silenced, with only the maternal allele being active. However, in individuals with AS, the maternal loss of function of this gene leads to the complete absence of UBE3A expression, resulting in multiple pathological features. Clinically, children diagnosed with AS exhibit a characteristic behavioral phenotype, including a happy demeanor, frequent and unmotivated laughter, movement, speech impairment, severe intellectual disability, and sleep problems. Since its discovery in 1965, significant progress has been made in understanding the genetic and pathophysiological aspects of AS. However, despite these advances, the molecular mechanisms underlying the disease remain incompletely understood, and no effective treatment currently exists. Current therapies focus solely on symptom management, and no approach has yet succeeded in reactivating the silenced paternal UBE3A allele. Therefore, this review highlights the epigenetic aspects involved in the AS in order to provide a better understanding and clarification of the mechanisms, hopefully paving the way for future research to improve the treatment of affected individuals.]]> Wed, 31 Dec 1969 19:00:00 EST The myoblast methylome: multiple types of associations with chromatin and transcription. Sen S, Lacey M, Baribault C, Ponnaluri VKC, Esteve PO, Ehrlich KC, Meletta M, Pradhan S, Ehrlich M
Epigenetics (Dec 2025)

Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (., and ). In contrast, brain-specific was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The -linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.]]> Wed, 31 Dec 1969 19:00:00 EST CT Biomarkers for Phenotypic Biological Aging: Emerging Concepts and Advantages. Lee MH, Garrett JW, Liu D, Pickhardt PJ
Radiographics (Aug 2025)

Aging is a complex phenomenon reflecting the time-dependent accumulation of damage that results in progressive structural and functional decline, disease risk, and death. Chronological age (CA) is an imperfect measure of health but remains an important driver of health care decisions. Biological age (BA) is a construct that attempts to provide a more holistic evaluation of the cumulative effects of aging and aging-related disease. The emergence of "omics"-based aging clocks (eg, epigenomics) has improved BA estimation, but imaging remains underutilized. CT biomarkers of muscle, fat, aortic calcification, and bone are examples of biomarkers of aging that can be used to construct a BA model (ie, CT-based biological age). As opposed to cellular and subcellular "frailomics" used in existing BA models, CT biomarkers are accessible and reproducible and reflect big-picture net phenotypic effects of aging at the tissue level (eg, using tissue segmentation). Recent technological advancements and improvements in artificial intelligence (AI) technologies have transformed our understanding of aging, and rapid automated AI tools enable scaling of image-based approaches for population-level impact. The understandable nature of explainable AI imaging tools instills trust in a model's prediction compared with opaque black box methodologies. Automated imaging-based body composition tools also can be applied opportunistically in either a retrospective or prospective fashion without the need for additional imaging, specialized testing, or patient time. Using a CT-based phenotypic approach to BA estimation is a practical example of opportunistic imaging that could be used to improve existing medical decision making and risk prediction for individual patient and societal benefit in ways that existing frailomics have failed. RSNA, 2025 See the invited commentary by Pyrros and Siddiqui in this issue.]]> Wed, 31 Dec 1969 19:00:00 EST Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. Martin CL, Chen J, D'Alessio AS, Ward-Caviness CK, Ye A, Lodge EK, Ghastine L, Dhingra R, Jima DD, Murphy SK, Hoyo C
Epigenetics (Dec 2025)

Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.]]> Wed, 31 Dec 1969 19:00:00 EST Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis. Kulecka M, O'Sullivan J, Fitzgerald R, Velikonja A, Huseyin CE, Laserna-Mendieta EJ, Ruiz-Limón P, Eckenberger J, Vidal-Marín M, Truppel BA, Singh R, Naik S, Croft NM, Temko A, Zomer A, MacSharry J, Melgar S, Deb P, Sanderson IR, Claesson MJ
Nat Commun (Aug 2025)

Current first-line treatments of paediatric ulcerative colitis (UC) maintain a 6-month remission in only half of the patients. Relapse prediction at diagnosis could enable earlier introduction of immunosuppressants. We collected intestinal biopsies from 56 treatment-naïve children, combining mucosal quantitative microbial profiling with host epigenomics, transcriptomics, genotyping, and in vitro and in vivo experiments on selected bacteria. Baseline bacterial diversity is lower in relapsing children, who have fewer butyrate producers but more oral-associated bacteria, whereof Veillonella parvula induces inflammation in epithelial cell lines and IL10 mice. Microbiota has the strongest association with future relapse, followed by host epigenome and transcriptome. Interferon gamma signalling is also linked to relapse-associated bacteria. Relapse-prediction using separate omics data is outperformed by a robust machine learning approach combining microbiomes and epigenomes. In summary, host-microbe data have prognostic potential in paediatric UC. Our translational findings also suggest that pro-inflammatory oral-associated colonizers can exploit the reduced colonic bacterial diversity of relapsing children.]]> Wed, 31 Dec 1969 19:00:00 EST use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes. Mmatli M, Mbelle NM, Fourie B, Osei Sekyere J
Virulence (Dec 2025)

Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs).]]> Wed, 31 Dec 1969 19:00:00 EST Dot1L-H3K79me2-Tbx6 Axis: A Novel Therapeutic Target for Preventing Cardiac Failure. Peralta TM, Zelarayán LC
Circ Res (Aug 2025)

]]> Wed, 31 Dec 1969 19:00:00 EST Host-microbe multi-omics and succinotype profiling have prognostic value for future relapse in patients with inflammatory bowel disease. O'Sullivan J, Patel S, Leventhal GE, Fitzgerald RS, Laserna-Mendieta EJ, Huseyin CE, Konstantinidou N, Rutherford E, Lavelle A, Dabbagh K, DeSantis TZ, Shanahan F, Temko A, Iwai S, Claesson MJ
Gut Microbes (Dec 2025)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory bowel disorders (IBD), the pathogenesis of which is uncertain but includes genetic susceptibility factors, immune-mediated tissue injury and environmental influences, most of which appear to act via the gut microbiome. We hypothesized that host-microbe alterations could be used to prognostically stratify patients experiencing relapses up to four years after endoscopy. We therefore examined multiple omics data, including published and new datasets, generated from paired inflamed and non-inflamed mucosal biopsies from 142 patients with IBD (54 CD; 88 UC) and from 34 control (non-diseased) biopsies. The relapse-predictive potential of 16S rRNA gene and transcript amplicons (standing and active microbiota) were investigated along with host transcriptomics, epigenomics and genetics. While standard single-omics analysis could not distinguish between patients who relapsed and those that remained in remission within four years of colonoscopy, we did find an association between the number of flares and a patient's succinotype. Our multi-omics machine learning approach was also able to predict relapse when combining features from the microbiome and human host. Therefore multi-omics, rather than single omics, better predicts relapse within 4 years of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.]]> Wed, 31 Dec 1969 19:00:00 EST and are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Daskeviciute D, Sainty B, Chappell-Maor L, Bone C, Russell S, Iglesias-Platas I, Arnaud P, Monteagudo-Sánchez A, Greenberg MVC, Chen K, Manerao-Azua A, Perez de Nanclares G, Lartey J, Monk D
Epigenetics (Dec 2025)

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, and , both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.]]> Wed, 31 Dec 1969 19:00:00 EST Deciphering sarcoidosis immunopathogenesis through systems biology. Jbeli AH, Crouser ED, Bhargava M
Curr Opin Pulm Med (Sep 2025)

Sarcoidosis is a complex, multisystem disease characterized by granulomatous inflammation and variable clinical outcomes. Its pathogenesis and progression are driven by intricate biological interactions, involving a complex interplay between patient-specific factors such as genetic background, sex, and environmental exposures, as well as epigenetic modifications that regulate gene expression and protein levels. These interconnected layers ultimately drive immune response to yet unidentified trigger(s), culminating in granuloma formation and, in some cases, with an aberrant repair response leading to irreversible organ dysfunction in some cases. In this review, we aim to synthesize recent multiomics research that unravels the underlying biological networks, offering a systems-level understanding of sarcoidosis.]]> Wed, 31 Dec 1969 19:00:00 EST Dynamic epigenomic landscape and gene regulatory networks during embryonic development in Pacific white shrimp (Litopenaeus vannamei) as revealed by histone modification profiling using CUT&Tag. Shi J, Qi Z, Yin M, Zeng Q, Hu J, Bao Z, Ye Z
Epigenetics Chromatin (Aug 2025)

The Pacific white shrimp (Litopenaeus vannamei) is the most widely farmed shrimp species globally, yet the epigenetic regulation underlying its embryonic development remains largely unexplored. Histone modifications are known to orchestrate gene expression during early development in model organisms, but their role in crustaceans is poorly understood.]]> Wed, 31 Dec 1969 19:00:00 EST Accounting for differences between Infinium MethylationEPIC v2 and v1 in DNA methylation-based tools. Zhuang BC, Jude MS, Konwar C, Yusupov N, Ryan CP, Engelbrecht HR, Whitehead J, Halberstam AA, MacIsaac JL, Dever K, Tran TK, Korinek K, Zimmer Z, Lee NR, McDade TW, Kuzawa CW, Huffman KM, Belsky DW, Binder EB, Czamara D, Korthauer K, Kobor MS
Life Sci Alliance (Sep 2025)

The recently launched Illumina Infinium MethylationEPIC v2.0 (EPICv2), successor of MethylationEPIC v1.0 (EPICv1), retains most of the probes in EPICv1, while expanding coverage of regulatory elements. The concordance between the two EPIC versions in DNA methylation-based tools has not yet been investigated. To address this, DNA methylation was profiled on both versions using matched blood samples across four cohorts spanning early to late adulthood. High concordance between versions at the array level but variable agreement at the individual probe level was noted. A significant contribution of the EPIC version to DNA methylation variation was observed, though it was to a smaller extent compared with sample relatedness and cell-type composition. Modest but significant differences in DNA methylation-based estimates between versions were observed, irrespective of the data preprocessing method used. Adjustments for EPIC version or calculation of estimates separately for each version largely mitigated these version-specific discordances. This work emphasizes the importance of accounting for EPIC version differences in research scenarios, especially in meta-analyses and longitudinal studies that require data harmonization across versions.]]> Wed, 31 Dec 1969 19:00:00 EST GenomicLayers: sequence-based simulation of epi-genomes. Gerrard DT
BMC Bioinformatics (Aug 2025)

Cellular development and differentiation in Eukaryotes depends upon sequential gene regulatory decisions that allow a single genome to encode many hundreds of distinct cellular phenotypes. Decisions are stored in the regulatory state of each cell, an important part of which is the epi-genome-the collection of proteins, RNA and their specific associations with the genome. Additionally, further cellular responses are, in part, determined by this regulatory state. To date, models of regulatory state have failed to include the contingency of incoming regulatory signals on the current epi-genetic state and none have done so at the whole-genome level.]]> Wed, 31 Dec 1969 19:00:00 EST Parent-of-origin effects on complex traits in up to 236,781 individuals. Hofmeister RJ, Cavinato T, Karimi R, van der Graaf A, Pajuste FD, Kronberg J, Taba N,  , Mägi R, Vaudel M, Rubinacci S, Johansson S, Milani L, Delaneau O, Kutalik Z
Nature (Aug 2025)

Parent-of-origin effects (POEs) occur when the effect of a genetic variant depends on its parental origin. Traditionally linked to genomic imprinting, POEs are believed to occur due to parental conflict over resource allocation to offspring, resulting in opposing parental influences. Despite their importance, POEs remain underexplored in complex traits, owing to the lack of parental genomes. Here we present an approach to infer the parent of origin of alleles without parental genomes, leveraging interchromosomal phasing, mitochondrial and X chromosome data, and sex-specific crossover in siblings. Applied to the UK Biobank, this enabled parent-of-origin inference for up to 109,385 individuals. Genome-wide association study scans for 59 complex traits and over 14,000 protein quantitative trait loci contrasting maternal and paternal effects identified over 30 POEs and confirmed more than 50% of known associations. More than one third of these showed opposite parental influences, especially for traits related to growth (for example, IGF1 and height) and metabolism (for example, type 2 diabetes and triglyceride levels). Replication in up to 85,050 individuals from the Estonian Biobank and 42,346 offspring from the Norwegian Mother, Father and Child Cohort Study (MoBa) validated 87% of testable associations. Overall, our findings highlight the contribution of POEs to complex traits and support the parental conflict hypothesis, providing compelling evidence for this understudied evolutionary phenomenon.]]> Wed, 31 Dec 1969 19:00:00 EST [Example of a genetic condition caused by an imprinting disorder: Angelman syndrome]. Coquisart C, Skouri S, Delplancq G, Spentchian M, Maneglier B, Guberto M, Brisset S
Ann Biol Clin (Paris) (Aug 2025)

An 18-months old boy was seen in a clinical genetics consultation with both his parents for a global developmental delay, hypotonia, post-natal microcephaly, as well as cognitive impairment including an absence of language acquisition. High throughput exome sequencing identified a pathogenic variant in the UBE3A gene that was inherited from his asymptomatic mother. This variant causes the child to lose the contribution of the maternal allele, through loss of UBE3A genetic expression. UBE3A is localized into a genomic imprinting region which undergoes transcriptional regulation based on parental origin, an epigenetic phenomenon described in certain specific regions of the human genome. Its expression is repressed on the paternal chromosome at locus 15q11-13. The truncating variant on the maternal allele then leads to a complete loss of UBE3A expression. This results in Angelman syndrome. Angelman syndrome is a genetic neurodevelopmental disorder whose transmission mode depends on the causative molecular mechanism, which consists of a lack of contribution from the maternal 15q11-q13 region. Angelman's phenotype and evolution varies according to causative molecular mechanism. Precise laboratory diagnosis is especially important for genetic counselling: in our patient's family, the recurrence risk amounts to 50 % in the event of a future pregnancy, and the family's relatives must me informed and offered medical counsel.]]> Wed, 31 Dec 1969 19:00:00 EST NanoTag is an improved method to map interactions between DNA and proteins not requiring IgG. Dimitriu MA, Arzate-Mejía RG, Steg LC, Germain PL, Mansuy IM
Sci Rep (Aug 2025)

Genome-wide profiling of DNA-protein interactions in cells can provide important information about mechanisms of gene regulation. Most current methods for genome-wide profiling of DNA-bound proteins such as ChIP-seq and CUT&Tag use conventional IgG antibodies to bind the target protein(s). This limits their applicability to targets with available high affinity and specificity antibodies and prevents their use for other targets. Here we describe NanoTag, an IgG-free method derived from CUT&Tag to profile DNA-protein interactions. NanoTag is based on a fusion between an anti-GFP nanobody and Tn5 transposase that can map GFP-tagged proteins associated with chromatin in a fast, cost-effective and animal-free manner. We used NanoTag to indirectly profile the histone mark H3K4me3 genome-wide via its binding partner TATA box-binding protein-associated factor 3 (TAF3) and the transcription factors Nanog and CTCF in mouse embryonic stem cells (mESCs). NanoTag results show high inter-replicate reproducibility, high signal-to-noise ratio and strong correlation with CUT&Tag datasets, validating its accuracy and reliability. NanoTag provides a novel, flexible and cost-effective IgG-free method to generate high resolution DNA-binding profiles in cells and tissues.]]> Wed, 31 Dec 1969 19:00:00 EST De novo assembly and delivery of synthetic megabase-scale human DNA into mouse early embryos. Liu Y, Zhou J, Liu D, Hu X, Yang L, Song XR, Jin XD, Xie W, Yang L, Liu Z, Yuan YJ
Nat Methods (Aug 2025)

Epigenetic modifications on natural chromosomes are inherited and maintained in a default state, making it challenging to remove intrinsic marks to study the fundamental principles of their establishment and further influence on transcriptional regulation. In this study, we developed SynNICE, a method for assembling and delivering intact, naive, synthetic megabase (Mb)-scale human DNA into early mouse embryos, to study de novo epigenetic regulation. By assembling and delivering a 1.14-Mb human AZFa (hAZFa) locus, we observed the spontaneous incorporation of murine histones and the establishment of DNA methylation at the one-cell stage. Notably, DNA methylation from scratch strongly enriches at repeat sequences without H3K9me3 reinforcement. Furthermore, the transcription of hAZFa initiated at the four-cell stage is regulated by newly established DNA methylation. This method provides a unique platform for exploring de novo epigenomic regulation mechanisms in higher animals.]]> Wed, 31 Dec 1969 19:00:00 EST Multigenerational exposure to DEHP drives dysregulation of imprinted gene Snurf to impair decidualization. Tan L, Gao R, Su Y, Zhang Y, Geng Y, Liu Q, Ma Y, Chen X, Li F, He J
J Hazard Mater (Aug 2025)

Phthalate-induced female reproductive health issues, particularly those related to di (2-ethylhexyl) phthalate (DEHP), are growing global concerns. Although most studies have focused on single-generation exposure, studies on prolonged DEHP exposure across multiple generations are limited. This study assessed the effects of multigenerational DEHP exposure on endometrial decidualization, which is crucial for embryo implantation. The results showed that sustained DEHP exposure over three generations exacerbated decidualization injury and led to adverse pregnancy outcomes. RNA sequencing revealed upregulation of the imprinted gene Snurf in the decidua, with changes that may not depend on alterations in DNA methylation. Knockdown of Snurf significantly alleviated in vitro decidualization deficiency induced by mono(2-ethylhexyl) phthalate (MEHP), the biologically active metabolite of DEHP. Proteomic analysis and the AlphaFold 3 algorithm indicated that Stn1 is a downstream target of Snurf, with silencing Stn1 resensitizing Snurf-knockdown stromal cells to MEHP. Human decidual stromal cells (hDSCs) from healthy participants showed sensitivity to MEHP, with the inhibition of decidualization. Epidemiological data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) indicated a positive association between DEHP exposure and female infertility. This study highlighted the cumulative toxic effects of multigenerational DEHP exposure on female reproduction and revealed the contribution of imprinted genes.]]> Wed, 31 Dec 1969 19:00:00 EST Mediators of maternal intergenerational epigenetic inheritance in mammals. Belton C, Kelsey G
Epigenomics (Aug 2025)

Experimental models and epidemiological data suggest that environmental factors, for example, adverse nutrition prior to conception, can lead to phenotypes in offspring of exposed parents in the absence of continued exposure. As a result these phenotypes have been described as epigentically inherited. The mechanistic basis for such phenomena has not been established in most cases. In this review, we consider possible contributing mechanisms for environmentaly induced epigenetic inheritance, with a focus on maternally transmitted effects and by comparing to paradigms of epigenetic inheritance with a clear mechanistic understanding. Genomic imprinting has provided an important conceptual framework for how the epigenetic states of parental germlines can determine allelic expression in offspring, yet, generally speaking, imprinted genes appear resilient to epigenetic disruption from altered parental environments. Metastable epialleles are environmentally sensitive and variably expressed loci that can impact organism phenotype, but the nature of any epigenetic marker at these loci transferred to offspring is unclear. Studies of examples across these forms of epigenetic inheritance show predominant effects are mediated by oocyte factors involved inreprogramming of the genome post-fertilization, rather than direct effects on gametic DNA methylation, with the exception of genomic imprinting. The potential contribution of additional oocyte chromatin features to the specific liability of phenotypic effector genes and their potential to persist through this reprogramming, however, remains to be investigated.]]> Wed, 31 Dec 1969 19:00:00 EST