Bruno Oliveira-Lopes , Nuno Tiago Tavares , Rui Henrique , Carmen Jerónimo , João Lobo
{"title":"睾丸生殖细胞肿瘤和不孕症:探索男性生殖细胞向新的生物标志物和治疗的旅程中的表观遗传失调","authors":"Bruno Oliveira-Lopes , Nuno Tiago Tavares , Rui Henrique , Carmen Jerónimo , João Lobo","doi":"10.1016/j.bbcan.2025.189437","DOIUrl":null,"url":null,"abstract":"<div><div>The development of male germ cells comprises a series of differentiation events that culminate in the formation of spermatozoa. From the primordial germ cell (PGC) to the spermatid, an array of epigenetic events take place in different stages of life. Disruptions in these mechanisms due to external factors can ultimately lead to decreased fertility and to testicular germ cell tumors (TGCTs). In this review, we highlight how DNA methylation, histone modifications and non-coding RNAs (ncRNAs) contribute to normal male germ cell development and discuss how disturbances in this epigenetic machinery can compromise fertility and induce neoplasia. Furthermore, the bidirectional relationship between infertility and TGCTs is discussed. Finally, we disclose the utility of “epidrugs” and ncRNAs as promising therapeutic options and TGCT biomarkers, respectively.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189437"},"PeriodicalIF":9.7000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Testicular germ cell tumors and infertility: Exploring epigenetic dysregulation in the journey of the male germ cell towards new biomarkers and therapeutics\",\"authors\":\"Bruno Oliveira-Lopes , Nuno Tiago Tavares , Rui Henrique , Carmen Jerónimo , João Lobo\",\"doi\":\"10.1016/j.bbcan.2025.189437\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The development of male germ cells comprises a series of differentiation events that culminate in the formation of spermatozoa. From the primordial germ cell (PGC) to the spermatid, an array of epigenetic events take place in different stages of life. Disruptions in these mechanisms due to external factors can ultimately lead to decreased fertility and to testicular germ cell tumors (TGCTs). In this review, we highlight how DNA methylation, histone modifications and non-coding RNAs (ncRNAs) contribute to normal male germ cell development and discuss how disturbances in this epigenetic machinery can compromise fertility and induce neoplasia. Furthermore, the bidirectional relationship between infertility and TGCTs is discussed. Finally, we disclose the utility of “epidrugs” and ncRNAs as promising therapeutic options and TGCT biomarkers, respectively.</div></div>\",\"PeriodicalId\":8782,\"journal\":{\"name\":\"Biochimica et biophysica acta. Reviews on cancer\",\"volume\":\"1880 5\",\"pages\":\"Article 189437\"},\"PeriodicalIF\":9.7000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochimica et biophysica acta. Reviews on cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0304419X25001799\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Reviews on cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304419X25001799","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Testicular germ cell tumors and infertility: Exploring epigenetic dysregulation in the journey of the male germ cell towards new biomarkers and therapeutics
The development of male germ cells comprises a series of differentiation events that culminate in the formation of spermatozoa. From the primordial germ cell (PGC) to the spermatid, an array of epigenetic events take place in different stages of life. Disruptions in these mechanisms due to external factors can ultimately lead to decreased fertility and to testicular germ cell tumors (TGCTs). In this review, we highlight how DNA methylation, histone modifications and non-coding RNAs (ncRNAs) contribute to normal male germ cell development and discuss how disturbances in this epigenetic machinery can compromise fertility and induce neoplasia. Furthermore, the bidirectional relationship between infertility and TGCTs is discussed. Finally, we disclose the utility of “epidrugs” and ncRNAs as promising therapeutic options and TGCT biomarkers, respectively.
期刊介绍:
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.