Sindik Neda, Pereza Nina, Dević Pavlić Sanja
Faculty of Medicine, Department of Medical Biology and Genetics, University of Rijeka, Braće Branchetta 20, 51000, Rijeka, Croatia.
Arch Gynecol Obstet. 2025 Feb;311(2):183-190. doi: 10.1007/s00404-024-07882-8. Epub 2024 Dec 18.
Epigenetic changes include all modifications affecting the expression of genes without changing the nucleotide sequence of the genome. Most studied epigenetic changes include DNA methylation, histone alterations and non-coding RNAs. DNA methylation is an important epigenetic mark, protecting the genome during gametogenesis and early embryo development. Demethylation process is a genome-wide event, taking place in two distinct waves during gametogenesis. The first event helps restore naïve pluripotency of the zygote, while the second event aids in the loss of parental epigenetic memory and facilitates specification of gametes. Histone modifications were recognized in murine and human primordial germ cells where their subsets condense chromatin, protecting it from dynamic changes taking place during gamete maturation. Deacetylation of histones was recognized as an important prerequisite of chromosomal segregation during metaphase II. Germline-specific ncRNAs and piRNAs are important in inhibiting transposon activity during gametogenesis, protecting overall genome stability. All epigenetic changes are prone to disruption, especially by exogenous factors. In recent years, with the increase in infertility, the association between assisted reproductive technology (ART) and its effects on epigenome remodeling of gametes have gained importance. The aim of this review is to summarize the epigenetic modifications crucial for oocyte development, while highlighting their role in reproductive disorders and ART.
表观遗传变化包括所有影响基因表达但不改变基因组核苷酸序列的修饰。研究最多的表观遗传变化包括DNA甲基化、组蛋白改变和非编码RNA。DNA甲基化是一种重要的表观遗传标记,在配子发生和早期胚胎发育过程中保护基因组。去甲基化过程是一个全基因组范围的事件,在配子发生过程中以两种不同的波发生。第一个事件有助于恢复合子的原始多能性,而第二个事件有助于消除亲本表观遗传记忆并促进配子的特化。组蛋白修饰在小鼠和人类原始生殖细胞中被识别,其亚组使染色质浓缩,保护其免受配子成熟过程中发生的动态变化影响。组蛋白去乙酰化被认为是减数分裂中期II染色体分离的重要前提。生殖系特异性非编码RNA和piRNA在配子发生过程中抑制转座子活性、保护整体基因组稳定性方面很重要。所有表观遗传变化都容易受到干扰,尤其是受到外源因素的干扰。近年来,随着不孕症的增加,辅助生殖技术(ART)与其对配子表观基因组重塑的影响之间的关联变得越来越重要。本综述的目的是总结对卵母细胞发育至关重要的表观遗传修饰,同时强调它们在生殖障碍和ART中的作用。