Department of Women's and Children's Health and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, Naples, Italy.
Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry SMS, University of Salerno, Salerno, Italy.
Clin Epigenetics. 2024 Jun 22;16(1):82. doi: 10.1186/s13148-024-01683-1.
Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls.
Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin).
The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.
遗传和环境因素都与许多发育过程有关。然而，最近的证据表明，表观遗传变化也可能影响青春期的开始或一生中易患多种疾病的倾向。本研究旨在通过分析来自三个不同组别的受试者的人外周血白细胞，来研究与青春期开始相关的基因组 DNA 甲基化谱的变化：19 名患有中枢性性早熟 (CPP) 的女孩、14 名年龄匹配的健康青春期前女孩和 13 名青春期阶段匹配的健康青春期女孩。为此，将 CPP 患者与青春期前和青春期前的对照组进行比较，以确定正常青春期过渡和 CPP 与青春期前和青春期前的对照组之间的变化。
与正常青春期过渡相关的甲基化变化分析确定了 1006 个差异甲基化 CpG 位点，其中 86%在青春期前的对照组中呈高甲基化。这些 CpG 位点中的一些位于与初潮年龄相关的基因或参与青春期发育过程的转录因子中。CPP 患者的甲基组谱分析显示，与青春期前和青春期对照组相比，分别有 65%和 55%的 CpG 位点呈低甲基化。此外，有趣的是，我们的结果显示存在 43 个差异甲基化基因，这些基因编码锌指 (ZNF) 蛋白。在研究的三组中进行的基因本体论和 IPA 分析显示，它们在一些与神经元通讯 (神经鞘和味觉途径)、雌激素作用、某些癌症 (特别是乳腺癌和卵巢癌) 或代谢 (特别是沉默调节蛋白) 相关的途径中显著富集。
正常和性早熟青春期女孩的不同甲基化谱表明，人类青春期的调节与特定的表观遗传变化有关。差异甲基化基因包括 ZNF 基因，它们可能在发育控制中发挥作用。此外，我们的数据强调了决定 GnRH 神经元迁移和功能以及代谢和肿瘤性疾病开始的信号通路中基因的甲基化状态变化，这些变化可能与 CPP 相关。
