Epigenetics最新文献_第3页

Placental malaria induces a unique methylation profile associated with fetal growth restriction. 胎盘疟疾诱导与胎儿生长限制相关的独特甲基化谱。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-06 DOI: 10.1080/15592294.2025.2475276

Nida Ozarslan, Corina Mong, John Ategeka, Lin Li, Sirirak Buarpung, Joshua F Robinson, Jimmy Kizza, Abel Kakuru, Moses R Kamya, Grant Dorsey, Philip J Rosenthal, Stephanie L Gaw

{"title":"Placental malaria induces a unique methylation profile associated with fetal growth restriction.","authors":"Nida Ozarslan, Corina Mong, John Ategeka, Lin Li, Sirirak Buarpung, Joshua F Robinson, Jimmy Kizza, Abel Kakuru, Moses R Kamya, Grant Dorsey, Philip J Rosenthal, Stephanie L Gaw","doi":"10.1080/15592294.2025.2475276","DOIUrl":"10.1080/15592294.2025.2475276","url":null,"abstract":"Fetal growth restriction (FGR) is associated with perinatal death and adverse birth outcomes, as well as long-term complications, including increased childhood morbidity, abnormal neurodevelopment, and cardio-metabolic diseases in adulthood. Placental epigenetic reprogramming associated with FGR may mediate these long-term outcomes. Placental malaria (PM), characterized by sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous space, is the leading global cause of FGR, but its impact on placental epigenetics is unknown. We hypothesized that placental methylomic profiling would reveal common and distinct mechanistic pathways of non-malarial and PM-associated FGR. We analyzed placentas from a US cohort with no malaria exposure (n = 12) and a cohort from eastern Uganda, a region with a high prevalence of malaria (n = 12). From each site, 8 cases of FGR and 4 healthy controls were analyzed. PM was diagnosed by placental histopathology. We compared the methylation levels of over 850K CpGs of the placentas using Infinium MethylationEPIC v1 microarray. Non-malarial FGR was associated with 65 differentially methylated CpGs (DMCs), whereas PM-FGR was associated with 133 DMCs, compared to their corresponding controls without FGR. One DMC (cg16389901, located in the promoter region of BMP4) was commonly hypomethylated in both groups. We identified 522 DMCs between non-malarial FGR vs. PM-FGR placentas, independent of differing geographic location or cellular composition. Placentas with PM-associated FGR have distinct methylation profiles compared to placentas with non-malarial FGR, suggesting novel epigenetic reprogramming in response to malaria. Larger cohort studies are needed to determine the distinct long-term health outcomes in PM-associated FGR pregnancies.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2475276"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic signatures of maternal-fetal health: insights from cord blood and placenta. 母胎健康的表观遗传特征：来自脐带血和胎盘的见解。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-23 DOI: 10.1080/15592294.2025.2508067

Jagadeesh Puvvula, Joseph M Braun, Emily A DeFranco, Shuk-Mei Ho, Yuet-Kin Leung, Shouxiong Huang, Xiang Zhang, Ann M Vuong, Stephani S Kim, Zana Percy, Aimin Chen

{"title":"Epigenetic signatures of maternal-fetal health: insights from cord blood and placenta.","authors":"Jagadeesh Puvvula, Joseph M Braun, Emily A DeFranco, Shuk-Mei Ho, Yuet-Kin Leung, Shouxiong Huang, Xiang Zhang, Ann M Vuong, Stephani S Kim, Zana Percy, Aimin Chen","doi":"10.1080/15592294.2025.2508067","DOIUrl":"10.1080/15592294.2025.2508067","url":null,"abstract":"The placenta is vital for fetal growth, and its methylation patterns reflect placental function, affecting the fetus and providing insights into disease origins. While cord blood methylation is convenient for assessing the fetal environment, methylation profiles vary by tissue due to variance in cell populations, function, and life stage. As tissue differences extensively contribute to the DNA methylation patterns, using surrogate samples such as cord blood may result in inconsistent findings. In this study, we aim to quantify the correlation of cytosine-phosphate-guanine dinucleotides (CpGs) between paired cord blood and placenta samples. Using the Infinium Human Methylation 450 K BeadChip, we compared methylation patterns in cord blood mononuclear cells (CBMC; n = 54), the maternally-facing side of placental tissue (MP; n = 68), and the fetal-facing side of placental tissue (FP; n = 67). Methylation patterns from the FP (6,021 CpGs) were significantly correlated with CBMC compared to the MP (2,862 CpGs). These CpGs were related to the biological (mitotic cell) process and molecular function (ribonucleoprotein complex binding). Our findings quantified CpG site correlation between cord blood and placenta, providing a valuable reference for future studies on placental health that rely on cord blood methylation in the absence of placental biospecimens.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2508067"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methylation profile of individuals with sickle cell trait. 镰状细胞特征个体的甲基化谱。

IF 3.2 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-08-04 DOI: 10.1080/15592294.2025.2539234

Ana Gabriela Vasconcelos, Mari Johnson, Yanwei Cai, Li Hsu, Nora Franceschini, Paul L Auer, Charles Kooperberg, Laura M Raffield, Alex P Reiner

{"title":"Methylation profile of individuals with sickle cell trait.","authors":"Ana Gabriela Vasconcelos, Mari Johnson, Yanwei Cai, Li Hsu, Nora Franceschini, Paul L Auer, Charles Kooperberg, Laura M Raffield, Alex P Reiner","doi":"10.1080/15592294.2025.2539234","DOIUrl":"10.1080/15592294.2025.2539234","url":null,"abstract":"Sickle cell trait (SCT) is due to heterozygosity for the β-globin sickle cell mutation. SCT recently has been associated with increased risk of various adverse health outcomes. DNA methylation (DNAm) is one potential mechanism by which SCT may impact disease risk. To identify DNAm sites associated with SCT, we conducted an epigenome-wide association (EWAS) meta-analysis using whole blood Illumina EPIC array data available in a total of 3,677 African American participants (including 1,071 with SCT) from the Women's Health Initiative and Jackson Heart Study. We identified 103 differentially methylated CpGs and 119 differentially methylated regions associated with SCT. The strongest signals were hypermethylated cis loci within predicted regulatory elements within or near the β-globin gene cluster on chromosome 11. Beyond the globin locus, SCT-associated DMPs were enriched in genes involved in redox regulation and oxidative stress. We also demonstrate an association of SCT with differences in biological age and epigenetic age acceleration, though the pattern and strength of association differ according to the epigenetic clock used. Specifically, more recent epigenetic clocks that incorporate clinical phenotypes or laboratory biomarkers related to adverse health outcomes are associated with accelerated aging among individuals with SCT compared to African American controls. Our results lay the groundwork for future study of the role of DNAm in biologic aging and related health outcomes among individuals with SCT.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2539234"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts. 性别分层piRNA表达分析揭示围产期铅（Pb）暴露对小鼠心脏功能的共同影响。

IF 3.2 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-08-10 DOI: 10.1080/15592294.2025.2542879

Kimberley E Sala-Hamrick, Kai Wang, Bambarendage P U Perera, Maureen A Sartor, Laurie K Svoboda, Dana C Dolinoy

{"title":"Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts.","authors":"Kimberley E Sala-Hamrick, Kai Wang, Bambarendage P U Perera, Maureen A Sartor, Laurie K Svoboda, Dana C Dolinoy","doi":"10.1080/15592294.2025.2542879","DOIUrl":"10.1080/15592294.2025.2542879","url":null,"abstract":"The landscape of PIWI-interacting RNA (piRNA) expression in the heart is poorly understood, particularly regarding sex differences. Altered piRNA expression has been reported in cardiovascular disease (CVD), and although exposure to the metal lead (Pb) is strongly associated with CVD risk, no studies have investigated Pb's effects on cardiac piRNAs. This study aimed to characterize piRNA expression in the murine heart and assess sex-specific effects of human-relevant maternal Pb exposure on adult offspring cardiac piRNA expression. piRNAs were identified from whole mouse hearts using sodium periodate exclusion of small RNA and subsequent sequencing. Control mice expressed 18,956 piRNAs in combined-sex analysis; sex-specific analyses revealed 9,231 piRNAs in female hearts and 5,972 piRNAs in male hearts. Genomic mapping showed 28-41% aligned to introns, while 12-28% mapped to exons. Comparing control and Pb-exposed hearts, we found more potential Pb-induced expression changes in females (847) compared to males (187) (p-value < 0.05 and |logFC| > 1). These piRNAs were significantly enriched near genes involved in biological processes related to heart function and CVD development, including mitochondrial function, energy metabolism, and cardiac muscle structure (FDR < 0.05). Overall, we characterized combined and sex-stratified piRNA expression in both control and Pb-exposed murine hearts. In addition to providing a foundation for sex-specific piRNA expression in the heart, these findings suggest a novel epigenetic mechanism by which developmental Pb exposure may impact CVD risk later in life. Future studies will link these sex-specific molecular changes to Pb-induced alterations in cardiac function.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2542879"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci. 基于CpG位点相对甲基化顺序的黑色素瘤定性预后生物标志物。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-04-03 DOI: 10.1080/15592294.2025.2487316

Yue Huo, Yaru Gao, Jiayi Ruan, Lingli Wang, Hongdong Li, Guini Hong

{"title":"A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci.","authors":"Yue Huo, Yaru Gao, Jiayi Ruan, Lingli Wang, Hongdong Li, Guini Hong","doi":"10.1080/15592294.2025.2487316","DOIUrl":"10.1080/15592294.2025.2487316","url":null,"abstract":"Skin cutaneous melanoma (SKCM) is an aggressive tumor with a poor prognosis. We developed SKCM-P8, a novel qualitative prognostic biomarker based on the relative methylation orderings of eight pairs of loci. Analysis of a training cohort and two independent validation datasets revealed a significant difference in overall survival between high- and low-risk groups stratified by SKCM-P8 (p < 0.05, log-rank test), with average area under the curve values of 0.83, 0.80, and 0.61, respectively. The differential methylation loci between high- and low-risk patients were enriched in immune-related biological processes and signaling pathways. Furthermore, low-risk patients exhibited higher CD8+ T cells and B levels, while high-risk patients had higher monocytes. The methylation levels of SKCM-P8 were also correlated with immune cell levels, indicating that they can reflect prognosis-related immune information. The low-risk group had a significantly higher mutation burden (p < 0.05, Wilcoxon test), suggesting potential benefits from immune checkpoint inhibitors. Patients stratified by SKCM-P8 displayed differential responses to therapy and immunotherapy (p < 0.05, Wilcoxon test), with low-risk patients showing better sensitivity and response. Furthermore, SKCM-P8 demonstrated super-predictive accuracy compared to six published models. Overall, SKCM-P8 offers a promising tool for predicting prognosis and guiding therapeutic decisions in SKCM.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2487316"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle. 洞察WDR5：揭示其功能、调控和对骨骼肌的影响。

IF 3.2 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-10-13 DOI: 10.1080/15592294.2025.2573998

Erick Bahena-Culhuac, Mauricio Hernández-Somilleda, José Manuel Hernández-Hernández

{"title":"Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.","authors":"Erick Bahena-Culhuac, Mauricio Hernández-Somilleda, José Manuel Hernández-Hernández","doi":"10.1080/15592294.2025.2573998","DOIUrl":"https://doi.org/10.1080/15592294.2025.2573998","url":null,"abstract":"WD40-repeat-containing protein 5 (WDR5) is a highly conserved multifunctional scaffold protein with a toroidal structure, facilitating interactions with numerous partners through its WDR5-binding motif (WBM) and WDR5-interacting (WIN) sites. It plays a critical role in histone modifications, including H3K4 methylation (H3K4me), histone acetylation, and deacetylation, influencing stem cell maintenance and differentiation. Recent studies highlight its involvement in muscle homeostasis, particularly in skeletal muscle progenitor cells, where it regulates PAX7-driven myogenic factor expression. Additionally, WDR5 governs epigenetic programs in smooth muscle by modulating H3K4me marks on lineage-specific genes. Despite extensive research on its role in cancer and chromatin remodeling, its broader physiological functions remain underexplored. This review examines WDR5's regulatory mechanisms, including its modulation by long non-coding RNAs (lncRNAs), post-translational modifications (PTMs), and microproteins, while emphasizing its relevance to muscle biology. Understanding WDR5's interactome and regulatory networks could provide novel insights into muscle regeneration, stem cell dynamics, and potential therapeutic strategies for muscular disorders and regenerative medicine.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2573998"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic remodeling of sheep oocytes and embryos induced by maternal methionine supplementation. 母体补充蛋氨酸诱导绵羊卵母细胞和胚胎的表观遗传重塑。

IF 3.2 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1080/15592294.2025.2567459

Jessica Townsend, Mehmet Kizilaslan, Zeynep Kizilaslan, Todd Taylor, Hasan Khatib

{"title":"Epigenetic remodeling of sheep oocytes and embryos induced by maternal methionine supplementation.","authors":"Jessica Townsend, Mehmet Kizilaslan, Zeynep Kizilaslan, Todd Taylor, Hasan Khatib","doi":"10.1080/15592294.2025.2567459","DOIUrl":"10.1080/15592294.2025.2567459","url":null,"abstract":"Environmental factors can influence gene expression and developmental outcomes through epigenetic modifications. Although maternal diet influences offspring DNA methylation and phenotypes, its effects on the oocyte and the resulting embryonic epigenome remain poorly understood. Here, we investigated the effect of maternal methionine supplementation on DNA methylation patterns in oocytes and embryos in Polypay sheep. Whole-genome bisulfite sequencing (WGBS) was performed on oocytes collected from 16 twin ewe pairs (8 methionine-treated and 8 controls). These ewes were later bred to control rams, and embryos were flushed for WGBS as well. In oocytes, 2,056 differentially methylated cytosines (DMCs) were identified. Additionally, 17 mitochondrial DMCs were identified, with 12 hypermethylated and 5 hypomethylated. In embryos, 113 DMCs were identified. Mitochondrial DNA analysis revealed 22 hypermethylated DMCs. To assess the inheritance of methyl marks, we compared DMCs between oocytes and embryos. While no direct overlaps were found in nuclear DNA, 3 CpGs exhibited opposite methylation trends - hypomethylated in oocytes but hypermethylated in embryos. In contrast, 5 mitochondrial DMCs overlapped between oocytes and embryos. To functionally assess the role of differentially methylated genes, we performed siRNA-mediated knockdown of 2 embryo DMC-associated genes: SCRIB and CERS3. Knockdown of SCRIB led to a 16.4% average decrease in blastocyst formation rate (p = 0.001), while CERS3 knockdown resulted in a 9.5% decrease (p = 0.005). These results demonstrate that maternal methionine supplementation alters nuclear and mitochondrial DNA methylation in oocytes and embryos, and that affected genes may play critical roles in early embryonic development, contributing to fetal programming.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2567459"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA methylation markers of insulin resistance surrogate measures in the Atherosclerosis Risk in Communities (ARIC) study. 社区动脉粥样硬化风险（ARIC）研究中胰岛素抵抗的DNA甲基化标志物替代措施

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-06 DOI: 10.1080/15592294.2025.2498857

Jeewoen Shin, Jan Bressler, Megan L Grove, Michael Brown, Elizabeth Selvin, James S Pankow, Myriam Fornage, Alanna C Morrison, Chloé Sarnowski

{"title":"DNA methylation markers of insulin resistance surrogate measures in the Atherosclerosis Risk in Communities (ARIC) study.","authors":"Jeewoen Shin, Jan Bressler, Megan L Grove, Michael Brown, Elizabeth Selvin, James S Pankow, Myriam Fornage, Alanna C Morrison, Chloé Sarnowski","doi":"10.1080/15592294.2025.2498857","DOIUrl":"https://doi.org/10.1080/15592294.2025.2498857","url":null,"abstract":"Insulin resistance (IR) is a risk factor for cardiovascular diseases and type 2 diabetes. Associations between DNA methylation (DNAm) and IR have been less studied in African ancestry (AA) populations than those of European ancestry (EA). We aimed to identify associations between whole blood DNAm and IR in up to 1,811 AA and 964 EA participants from the Atherosclerosis Risk in Communities (ARIC) study. We quantified IR using three surrogate measures: the homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride-glucose index (TyG), and the triglyceride glucose-body mass index (TyG-BMI). We used ancestry-stratified linear regression models to conduct epigenome-wide association studies of IR, adjusting for batch effects and relevant covariates. Among 484,436 tested CpG sites, 39 were significantly associated with IR, of which 31% (10 in AA and two in EA) were associated with TyG-BMI and not previously reported for IR or related traits. These include a positive association at cg18335991-SEMA7A in AA. SEMA7A inhibits adipogenesis of preadipocytes and lipogenesis of mature adipocytes. DNAm levels at cg18335991 have been reported to be negatively associated with SEMA7A expression in blood. After additionally adjusting for smoking and drinking status, 15 of the 39 significant CpG sites remained significant or suggestive. Our study identified novel IR-associated CpG sites, contributing to a broader understanding of the epigenetic mechanisms underlying IR in diverse populations.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2498857"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Higher sperm H3K4me3 levels are associated with idiopathic recurrent pregnancy loss. 较高的精子H3K4me3水平与特发性复发性妊娠丢失有关。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-04-29 DOI: 10.1080/15592294.2025.2498859

Delna Irani, Deepshikha Arya, Deepti Tandon, Vandana Bansal, Anushree Patil, Dipty Singh

{"title":"Higher sperm H3K4me3 levels are associated with idiopathic recurrent pregnancy loss.","authors":"Delna Irani, Deepshikha Arya, Deepti Tandon, Vandana Bansal, Anushree Patil, Dipty Singh","doi":"10.1080/15592294.2025.2498859","DOIUrl":"https://doi.org/10.1080/15592294.2025.2498859","url":null,"abstract":"During fertilization, spermatozoa contribute genetic and epigenetic factors such as chromatin packaged with protamines and histones; DNA methylome, non-coding RNAs, etc. Human sperm chromatin retains 5-15% nucleosomes which can play a key role in embryonic development. Recurrent pregnancy loss (RPL) is a condition mainly attributed to defects in embryo and placenta development. Majority of the known RPL factors are of maternal contribution, while ~50% RPL cases are termed idiopathic (iRPL). In addition to paternal genetic factors, epigenetic factors via sperm could also be responsible for iRPL. Hence, we investigated alterations in retained nucleosome content of iRPL sperm (n = 46) as compared to fertile male population (n = 40). We measured the relative abundance of core histone H4 and Protamine-2 content along with the modified histones H4Ac, H3K4me3, H3K27me3 and H3K9me3 by flow cytometry. H4 and Protamine-2 levels were comparable in both groups and showed significant negative correlation. The iRPL group had significantly higher levels of sperm H3K4me3 as compared to the fertile control group. The other modified histones and protamine levels showed no significant alterations. Furthermore, sperm DFI was found to be significantly positively correlated with H4 levels in both groups. No significant correlation was observed between sperm 5-mC levels with H4 and other modified histone levels. A fraction of H3K4me3 enrichment is now known to resist embryonic epigenetic reprogramming; and hence, such elevated levels in the sperm would question its developmental competence leading to RPL pathology. Also, incidence of sperm DNA fragmentation is associated with increased histone retention in both fertile and iRPL cases.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2498859"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucocorticoid receptor epigenetic activity in the heart. 心脏中糖皮质激素受体的表观遗传活性。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-25 DOI: 10.1080/15592294.2025.2468113

Olukunle Akinborewa, Mattia Quattrocelli

{"title":"Glucocorticoid receptor epigenetic activity in the heart.","authors":"Olukunle Akinborewa, Mattia Quattrocelli","doi":"10.1080/15592294.2025.2468113","DOIUrl":"10.1080/15592294.2025.2468113","url":null,"abstract":"The glucocorticoid receptor (GR) is a critical nuclear receptor that regulates gene expression in diverse tissues, including the heart, where it plays a key role in maintaining cardiovascular health. GR signaling influences essential processes within cardiomyocytes, including hypertrophy, calcium handling, and metabolic balance, all of which are vital for proper cardiac function. Dysregulation of GR activity has been implicated in various cardiovascular diseases (CVDs), highlighting the potential of GR as a therapeutic target. Remarkably, recent insights into GR's epigenetic regulation and its interaction with circadian rhythms reveal opportunities to optimize therapeutic strategies by aligning glucocorticoid administration with circadian timing. In this review, we provide an overview of the glucocorticoid receptor's role in cardiac physiology, detailing its genomic and non-genomic pathways, interactions with epigenetic and circadian regulatory mechanisms, and implications for cardiovascular disease. By dissecting these molecular interactions, this review outlines the potential of epigenetically informed and circadian-timed interventions that could change the current paradigms of CVD treatments in favor of precise and effective therapies.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2468113"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0