Clinical Epigenetics最新文献

{"title":"MGMT epimutations and risk of incident cancer of the colon, glioblastoma multiforme, and diffuse large B cell lymphomas.","authors":"Oleksii Nikolaienko, Garnet L Anderson, Rowan T Chlebowski, Su Yon Jung, Holly R Harris, Stian Knappskog, Per E Lønning","doi":"10.1186/s13148-025-01835-x","DOIUrl":"10.1186/s13148-025-01835-x","url":null,"abstract":"<p><strong>Background: </strong>Constitutional BRCA1 epimutations (promoter hypermethylation) are associated with an elevated risk of triple-negative breast cancer and high-grade serous ovarian cancer. While MGMT epimutations are frequent in colon cancer, glioblastoma, and B-cell lymphoma, it remains unknown whether constitutional MGMT epimutations are associated with risk of any of these malignancies.</p><p><strong>Methods: </strong>We designed a nested case-control study, assessing potential associations between MGMT epimutations in blood from healthy individuals and subsequent risk of incident cancer. The study cohort was drawn from postmenopausal women, participating in the Women's Health Initiative (WHI) study, who had not been diagnosed with either colon cancer, glioblastoma, or B-cell lymphoma prior to study entry. The protocol included n = 400 women developing incident left-sided and n = 400 women developing right-sided colon cancer, n = 400 women developing diffuse large B-cell lymphomas, all matched on a 1:2 basis with cancer-free controls, and n = 195 women developing incident glioblastoma multiforme, matched on a 1:4 basis. All cancers were confirmed in centralized medical record review. Blood samples, collected at entry, were analyzed for MGMT epimutations by massive parallel sequencing. Associations between MGMT methylation and incident cancers were analyzed by Cox proportional hazards regression.</p><p><strong>Results: </strong>Analyzing epimutations affecting the key regulatory area of the MGMT promoter, the hazard ratio (HR) was 1.07 (95% CI 0.79-1.45) and 0.80 (0.59-1.08) for right- and left-sided colon cancer, respectively, 1.13 (0.78-1.64) for glioblastoma, and 1.11 (0.83-1.48) for diffuse large B-cell lymphomas. Sensitivity analyses limited to subregions of the MGMT promoter and to individuals with different genotypes of a functional SNP in the MGMT promoter (rs16906252), revealed no significant effect on HR for any of the cancer forms. Neither did we observe any effect of rs16906252 status on HR for any of the cancer forms among individuals methylated or non-methylated at the MGMT promoter.</p><p><strong>Conclusions: </strong>Constitutional MGMT promoter methylation in normal tissue is not associated with an increased risk of developing colon cancer, glioblastoma, or B-cell lymphoma.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"28"},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic utility of single-locus DNA methylation mark in Sotos syndrome developed by nanopore sequencing-based episignature.","authors":"Takeshi Mizuguchi, Nobuhiko Okamoto, Taiki Hara, Naoto Nishimura, Masamune Sakamoto, Li Fu, Yuri Uchiyama, Naomi Tsuchida, Kohei Hamanaka, Eriko Koshimizu, Atsushi Fujita, Kazuharu Misawa, Kazuhiko Nakabayashi, Satoko Miyatake, Naomichi Matsumoto","doi":"10.1186/s13148-025-01832-0","DOIUrl":"10.1186/s13148-025-01832-0","url":null,"abstract":"<p><strong>Background: </strong>In various neurodevelopmental disorders (NDDs), sets of differential methylation marks (referred to as DNA methylation signatures or episignatures) are syndrome-specific and useful in evaluating the pathogenicity of detected genetic variants. These signatures have generally been tested using methylation arrays, requiring additional experimental and evaluation costs. As an alternative, long-read sequencing can simultaneously and accurately evaluate genetic and epigenetic changes. In addition, genome-wide DNA methylation profiling with more complete sets of CpG using long-read sequencing (than methylation arrays) may provide alternative but more comprehensive DNA methylation signatures, which have yet to be adequately investigated.</p><p><strong>Methods: </strong>Nine and seven cases of molecularly diagnosed Sotos syndrome and ATR-X syndrome, respectively, were sequenced using nanopore long-read sequencing, together with 22 controls. Genome-wide differential DNA methylation analysis was performed. Among these differential DNA methylation sites, a single-locus DNA methylation mark at part of the NSD1 CpG island (CpGi) was subsequently studied in an additional 22 cases with a NSD1 point mutation or a 5q35 submicroscopic deletion involving NSD1. To investigate the potential utility of a single-locus DNA methylation test at NSD1 CpGi for differential diagnosis, nine cases with NSD1-negative clinically overlapping overgrowth intellectual disability syndromes (OGIDs) were also tested.</p><p><strong>Results: </strong>Long-read sequencing enabled the successful extraction of two sets of differential methylation marks unique to each of Sotos syndrome and ATR-X syndrome, referred to as long-read-based DNA methylation signatures (LR-DNAm signatures), as alternatives to reported DNA methylation signatures (obtained by methylation array). Additionally, we found that a part, but not all, of the NSD1 CpGi were hypomethylated compared with the level in controls in both cases harboring NSD1 point mutations and those with a 5q35 submicroscopic deletion. This difference in methylation is specific to Sotos syndrome and lacking in other OGIDs.</p><p><strong>Conclusions: </strong>Simultaneous evaluation of genetic and epigenetic alterations using long-read sequencing may improve the discovery of DNA methylation signatures, which may in turn increase the diagnostic yields. As an example of the outcomes of these analyses, we propose that a single-locus DNA methylation test at NSD1 CpGi may streamline the molecular diagnosis of Sotos syndrome, regardless of the type of NSD1 aberration.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"27"},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LSD1 is a targetable vulnerability in gastric cancer harboring TP53 frameshift mutations.","authors":"Suzeng Wang, Chunyu Yang, Junhui Tang, Kaiqing Wang, Hao Cheng, Surui Yao, Zhaohui Huang, Bojian Fei","doi":"10.1186/s13148-025-01829-9","DOIUrl":"10.1186/s13148-025-01829-9","url":null,"abstract":"<p><strong>Background: </strong>TP53 mutations are linked to aggressive progression and chemoresistance in gastric cancer (GC). Frameshift mutation is the second most common mutation type of TP53. However, the consequences of this mutation type in GC were not well understood, and targeted therapies for cancer patients harboring frameshift mutations were also not established. Histone methylation significantly influences tumorigenesis in TP53-mutated cancers, and related inhibitors are emerging as specific therapeutic strategies.</p><p><strong>Methods and results: </strong>By treating GC cell lines harboring various TP53 mutation types with a library of histone demethylase inhibitors, we identified that GSK690, a reversible inhibitor of lysine-specific demethylase 1 (LSD1), selectively inhibits GC cells harboring TP53 frameshift mutations without nuclear localization sequence (NLS) (termed TP53 Frameshift ^NLS), which accounts for 89% TP53 frameshift mutations in GC patients. GSK690 showed significant specific inhibition in vitro and in vivo against this subtype by inducing G1/S cell cycle arrest via the LSD1-CCNA2 axis. Importantly, dual-luciferase assays and ChIP-qPCR confirmed that the loss of transcriptional repression activities of p53 in drives LSD1 upregulation in TP53 Frameshift ^NLS cancer cells.</p><p><strong>Conclusions: </strong>In summary, our results indicate that the nuclear localization deficiency of p53 accounts for increased expression of LSD1 in TP53 Frameshift ^NLS GCs. GSK690 inhibits cell cycle progression and tumor growth by suppressing aberrantly activated LSD1-CCNA2 signaling in this GC subtype, counteracting malignant proliferation and thereby providing a precise therapeutic strategy for GC patients with TP53 Frameshift ^NLS.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"26"},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of 17 novel epigenetic biomarkers associated with anxiety disorders using differential methylation analysis followed by machine learning-based validation.","authors":"Yoonsung Kwon, Asta Blazyte, Yeonsu Jeon, Yeo Jin Kim, Kyungwhan An, Sungwon Jeon, Hyojung Ryu, Dong-Hyun Shin, Jihye Ahn, Hyojin Um, Younghui Kang, Hyebin Bak, Byoung-Chul Kim, Semin Lee, Hyung-Tae Jung, Eun-Seok Shin, Jong Bhak","doi":"10.1186/s13148-025-01819-x","DOIUrl":"10.1186/s13148-025-01819-x","url":null,"abstract":"<p><strong>Background: </strong>The changes in DNA methylation patterns may reflect both physical and mental well-being, the latter being a relatively unexplored avenue in terms of clinical utility for psychiatric disorders. In this study, our objective was to identify the methylation-based biomarkers for anxiety disorders and subsequently validate their reliability.</p><p><strong>Methods: </strong>A comparative differential methylation analysis was performed on whole blood samples from 94 anxiety disorder patients and 296 control samples using targeted bisulfite sequencing. Subsequent validation of identified biomarkers employed an artificial intelligence-based risk prediction models: a linear calculation-based methylation risk score model and two tree-based machine learning models: Random Forest and XGBoost.</p><p><strong>Results: </strong>Seventeen novel epigenetic methylation biomarkers were identified to be associated with anxiety disorders. These biomarkers were predominantly localized near CpG islands, and they were associated with two distinct biological processes: 1) cell apoptosis and mitochondrial dysfunction and 2) the regulation of neurosignaling. We further developed a robust diagnostic risk prediction system to classify anxiety disorders from healthy controls using the 17 biomarkers. Machine learning validation confirmed the robustness of our biomarker set, with XGBoost as the best-performing algorithm, an area under the curve of 0.876.</p><p><strong>Conclusion: </strong>Our findings support the potential of blood liquid biopsy in enhancing the clinical utility of anxiety disorder diagnostics. This unique set of epigenetic biomarkers holds the potential for early diagnosis, prediction of treatment efficacy, continuous monitoring, health screening, and the delivery of personalized therapeutic interventions for individuals affected by anxiety disorders.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"24"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiogenomic method combining DNA methylation profiles and magnetic resonance imaging radiomics predicts patient prognosis in skull base chordoma.","authors":"Xiaoyu Deng, Peiran Li, Kaibing Tian, Fan Zhang, Yumeng Yan, Yanghua Fan, Zhen Wu, Junting Zhang, Jiang Du, Wei Chen, Liang Wang","doi":"10.1186/s13148-025-01836-w","DOIUrl":"10.1186/s13148-025-01836-w","url":null,"abstract":"<p><strong>Background: </strong>Chordoma is a rare malignant bone tumor exhibiting poor survival and prognosis. Hence, it is crucial to develop a convenient and effective prognostic classification method for the rehabilitation and management of patients with chordoma. In this study, we combined DNA methylation profiles and magnetic resonance imaging (MRI) images to generate a radiogenomic signature to assess its effectiveness for prognosis classification in patients with skull base chordoma.</p><p><strong>Results: </strong>DNA methylation profiles from chordoma tissue samples of 40 patients were factorized into eight DNA methylation signatures. Among them, Signature 4 was identified as the prognosis-specific signature. Based on the Signature 4 loading values, the patients were categorized into low-signature (LLG) and high-signature (HLG) loading groups. HLG patients had higher progression-free survival times than LLG patients. Combined analysis with external single-cell RNA-seq data revealed higher tumor cell proportions and lower natural killer cell proportions in the HLG than in the LLG. Additionally, 2,553 radiomic features were extracted from T1, T2, and enhanced T1 MRI images of the patients, and a radiogenomic signature comprising 14 radiomic features was developed. In a validation cohort of 122 patients, the radiogenomic signature successfully distinguished between the two groups (P = 0.027). Furthermore, the existence of Signature 4 was confirmed in an additional dataset of 14 patients.</p><p><strong>Conclusion: </strong>We developed a prognostic radiogenomic signature using a radiogenomic classification method, which leverages MRI images to extract features that reflect the DNA methylation signature associated with prognosis, enabling the stratification of patients based on their prognostic risk. This method offers the advantages of being noninvasive and convenient.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"23"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOXA9 methylation is not associated with survival in Brazilian patients with lung adenocarcinoma.","authors":"Anna Luiza Silva Almeida Vicente, Fabiana Aparecida de Souza Santos, Welinton Yoshio Hirai, Delphine Lissa, Rodrigo de Oliveira Cavagna, Aline Larissa Virginio da Silva, Mariana Bisarro Dos Reis, Eduardo Caetano Albino da Silva, Flávio Augusto Ferreira da Silva, Josiane Dias Mourão, Pedro De Marchi, Ana Carolina de Carvalho, Letícia Ferro Leal, Rui Manuel Reis","doi":"10.1186/s13148-025-01831-1","DOIUrl":"10.1186/s13148-025-01831-1","url":null,"abstract":"<p><p>Homeobox A9 promoter methylation (HOXA9) has been reported as a biomarker for early lung adenocarcinoma patients' prognosis. We aim to evaluate its prognostic value, regardless of disease stage. Using droplet digital PCR, we measured HOXA9 methylation in a cohort comprising 161 Brazilian patients. Low HOXA9 methylation was associated with higher cancer-specific survival but showed no significance after adjustment for clinical covariates. While low HOXA9 methylation was associated with earlier stages, no survival association was observed in this subset of patients. Overall, HOXA9 promoter methylation is not an independent prognostic biomarker of cancer-specific survival in Brazilian lung adenocarcinomas patients.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"25"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation-based telomere length is more strongly associated with long-term all-cause mortality than quantitative polymerase chain reaction-based telomere length among middle-aged and older hypertensive adults.","authors":"Qianhui Wang, Yuanfeng Gao, Dilare Taiwaikuli, Huanhuan Ding, Jie Song, Xinchun Yang, Baopeng Tang, Xianhui Zhou","doi":"10.1186/s13148-025-01833-z","DOIUrl":"10.1186/s13148-025-01833-z","url":null,"abstract":"<p><strong>Background: </strong>Telomere length (TL) has been linked to mortality risk across various populations. However, its predictive value for mortality risk specifically in hypertensive adults remains unclear.</p><p><strong>Methods: </strong>This cohort study utilized data from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition Examination Survey (NHANES). TL was assessed using DNA methylation (DNAmTL) and quantitative polymerase chain reaction (qPCRTL). Cox proportional hazards models were employed to examine the relationship between TL and mortality risk.</p><p><strong>Results: </strong>This study included 1601 participants, with 988 deaths occurring during a median follow-up of 184 months, including 279 from cardiovascular disease (CVD). Deceased participants exhibited significantly lower levels of DNAmTL (6.45 ± 0.30 vs. 6.70 ± 0.28, P < 0.001) and qPCRTL (0.89 ± 0.22 vs. 0.99 ± 0.24, P < 0.001) compared to survivors. After full adjustment, each 1-kb decrement in DNAmTL and qPCRTL was associated with a 52% and 38% reduction in all-cause mortality risk, respectively. Participants in the highest TL quartile (Q4) for DNAmTL and qPCRTL had a 36% and 25% reduced risk of all-cause mortality than those in the lowest quartile (Q1), respectively. Receiver operating characteristic (ROC) curves demonstrated that DNAmTL had superior predictive value compared to qPCRTL (area under curve [AUC] 0.73 vs. 0.63, P < 0.001).</p><p><strong>Conclusion: </strong>TL is inversely associated with all-cause mortality risk in middle-aged and older hypertensive adults, with DNAmTL showing greater predictive accuracy for long-term mortality than qPCRTL.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"22"},"PeriodicalIF":4.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific role of epigenetic modification of a leptin upstream enhancer in adipose tissue.","authors":"Luise Müller, Rebecca Oelkrug, Jens Mittag, Anne Hoffmann, Adhideb Ghosh, Falko Noé, Christian Wolfrum, Esther Guiu Jurado, Nora Klöting, Arne Dietrich, Matthias Blüher, Peter Kovacs, Kerstin Krause, Maria Keller","doi":"10.1186/s13148-025-01830-2","DOIUrl":"10.1186/s13148-025-01830-2","url":null,"abstract":"<p><strong>Objective: </strong>Maternal hormonal status can have long-term effects on offspring metabolic health and is likely regulated via epigenetic mechanisms. We elucidated the effects of maternal thyroid hormones on the epigenetic regulation of leptin (Lep) transcription in adipose tissue (AT) and subsequently investigated the role of DNA methylation at a Lep upstream enhancer (UE) in adipocyte biology.</p><p><strong>Results: </strong>Pregnant mice treated with triiodothyronine (T3) produced offspring with reduced body weight, total fat mass, and gonadal white adipose tissue (gWAT) mass at 6 months of age (treatment: N = 8; control: N = 12). Compared with control offspring, exclusively female offspring of T3-treated mothers presented lower Lep mRNA levels and higher Lep UE methylation in gWAT. In murine preadipocytes, targeted demethylation of the Lep UE via a dCas9-SunTag-TET1 system reduced methylation by ~ 20%, but this effect was insufficient to alter Lep expression or lipid accumulation after differentiation. In human omental visceral AT (OVAT) samples from the Leipzig Obesity BioBank (LOBB, N = 52), LEP UE methylation was associated with body fat percentage, and mediation analysis indicated that leptin serum levels partially mediate this association exclusively in females.</p><p><strong>Conclusion: </strong>Findings from the animal model suggest that maternal thyroid hormones influence offspring gWAT Lep expression in a sex-specific manner, potentially through changes in Lep UE methylation. However, in vitro experiments indicate that Lep UE methylation alone is not sufficient to regulate Lep expression or adipocyte lipid accumulation. In humans with obesity, LEP UE methylation is associated with body fat percentage, with leptin serum levels potentially acting as a mediator exclusively in females.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"21"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitrification affects the post-implantation development of mouse embryos by inducing DNA damage and epigenetic modifications.","authors":"Yurong Chen, Haibo Zhu, Fucheng Guo, Luyao Wang, Wenli Zhang, Ruizhi Liu, Xiaoling Zhang, Xiangpeng Dai","doi":"10.1186/s13148-025-01826-y","DOIUrl":"10.1186/s13148-025-01826-y","url":null,"abstract":"<p><p>Vitrification is widely used in assisted reproductive technology (ART) for female infertility, but the long-term effect on the embryo of vitrification has not been comprehensively studied. The study aimed to investigate the effect of vitrification on long-term development of mouse embryos. The warmed embryos which were frozen at 8-cell stage were cultured in vitro until the blastocyst stage and were transferred into recipients. Immunofluorescence staining was performed to evaluate the reactive oxygen species (ROS) level, mitochondrial function, cell apoptosis, DNA damage and histone epigenetic modification in blastocysts. Transmission electron microscopy (TEM) analysis was performed to exam the mitochondrial ultrastructure in blastocysts. The related gene expression and transcriptome profiles were investigated by RT-qPCR and RNA-seq, respectively. Blastocyst and implantation frequencies were not significantly affected by vitrification. However, vitrification significantly reduced blastocyst cell number and the live pup frequency. Vitrification induced ROS accumulation, DNA damage, and apoptosis in mouse blastocysts. The homologous recombination (NHEJ) is the major DNA repair pathway for vitrified embryos. Vitrification elevated H3K4me2/3, H4K12ac, and H4K16ac levels and reduced m⁶A modification in blastocysts. Moreover, vitrification significantly altered transcriptome profiles of mice placentas and brains at embryonic day 18.5 (E18.5). Thus, vitrification exhibited a long-term effect on mouse embryo viability by increasing ROS levels, DNA damage, altering the epigenetic modifications and transcriptome profiles.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"20"},"PeriodicalIF":4.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal maternal glycemia during pregnancy and placental epigenetic age acceleration.","authors":"Tesfa Dejenie Habtewold, Prabhavi Wijesiriwardhana, Richard J Biedrzycki, Cuilin Zhang, Katherine L Grantz, Jagteshwar Grewal, Fasil Tekola-Ayele","doi":"10.1186/s13148-025-01825-z","DOIUrl":"10.1186/s13148-025-01825-z","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of maternal glucose homeostasis has been related to an increased risk of morbidity and mortality in mothers and fetuses, yet the mechanism remains unclear. This study investigated the association between maternal glycemic levels and placental epigenetic age acceleration (PAA) in a multiethnic cohort.</p><p><strong>Methods: </strong>In a sample of 301 pregnant women (102 Hispanic, 77 White, 72 Black, and 50 Asian/Pacific Islander), the association of glycemic markers cumulative exposure with PAA was tested using linear regression adjusting for fetal sex, maternal age, educational status, and health insurance status. Models were applied in the full cohort and stratified by race/ethnicity. Further, sensitivity analyses were performed after excluding women with GDM or preeclampsia.</p><p><strong>Results: </strong>Among Black women, high glucose, HbA1c, and insulin cumulative exposure levels were associated with lower PAA compared to low cumulative exposure levels (β = - 0.75 weeks, 95% CI = - 1.41 to - 0.08); β = - 0.86, 95% CI = - 1.51 to - 0.21; and β = - 0.76, 95% CI = - 1.49 to - 0.03, respectively). Among Asian/Pacific Islander women, medium insulin cumulative exposure level was associated with lower PAA (β = - 0.94 weeks, 95% CI = - 1.74 to - 0.14). No significant association was observed among White and Hispanic women as well as in the full cohort.</p><p><strong>Conclusions: </strong>Elevated glucose, HbA1c, and insulin cumulative levels throughout pregnancy were associated with lower PAA in Black and Asian/Pacific Islander women. Placental epigenetic aging may be altered by maternal elevated glycemia and may in part underlie early programming of health outcomes in pregnancy and childhood health outcomes.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"19"},"PeriodicalIF":4.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}