Department of Histology and Embryology, Akdeniz University School of Medicine, Campus, 07070, Antalya, Turkey.
Histochem Cell Biol. 2022 Jul;158(1):79-95. doi: 10.1007/s00418-022-02102-3. Epub 2022 Apr 20.
Histone methylation is one of the main epigenetic mechanisms by which methyl groups are dynamically added to the lysine and arginine residues of histone tails in nucleosomes. This process is catalyzed by specific histone methyltransferase enzymes. Methylation of these residues promotes gene expression regulation through chromatin remodeling. Functional analysis and knockout studies have revealed that the histone lysine methyltransferases SETD1B, SETDB1, SETD2, and CFP1 play key roles in establishing the methylation marks required for proper oocyte maturation and follicle development. As oocyte quality and follicle numbers progressively decrease with advancing maternal age, investigating their expression patterns in the ovaries at different reproductive periods may elucidate the fertility loss occurring during ovarian aging. The aim of our study was to determine the spatiotemporal distributions and relative expression levels of the Setd1b, Setdb1, Setd2, and Cxxc1 (encoding the CFP1 protein) genes in the postnatal mouse ovaries from prepuberty to late aged periods. For this purpose, five groups based on their reproductive periods and histological structures were created: prepuberty (3 weeks old; n = 6), puberty (7 weeks old; n = 7), postpuberty (18 weeks old; n = 7), early aged (52 weeks old; n = 7), and late aged (60 weeks old; n = 7). We found that Setd1b, Setdb1, Setd2, and Cxxc1 mRNA levels showed significant changes among postnatal ovary groups (P < 0.05). Furthermore, SETD1B, SETDB1, SETD2, and CFP1 proteins exhibited different subcellular localizations in the ovarian cells, including oocytes, granulosa cells, stromal and germinal epithelial cells. In general, their levels in the follicles, oocytes, and granulosa cells as well as in the germinal epithelial and stromal cells significantly decreased in the aged groups when compared the other groups (P < 0.05). These decreases were concordant with the reduced numbers of the follicles at different stages and the luteal structures in the aged groups (P < 0.05). In conclusion, these findings suggest that altered expression of the histone methyltransferase genes in the ovarian cells may be associated with female fertility loss in advancing maternal age.
组蛋白甲基化是一种主要的表观遗传机制，通过该机制，甲基基团可以动态地添加到核小体中组蛋白尾巴的赖氨酸和精氨酸残基上。这个过程是由特定的组蛋白甲基转移酶催化的。这些残基的甲基化通过染色质重塑促进基因表达调控。功能分析和敲除研究表明，组蛋白赖氨酸甲基转移酶 SETD1B、SETDB1、SETD2 和 CFP1 在建立适当的卵母细胞成熟和卵泡发育所需的甲基化标记方面发挥着关键作用。随着母体年龄的增长，卵母细胞质量和卵泡数量逐渐减少，研究它们在不同生殖期的卵巢中的表达模式可能阐明卵巢衰老过程中发生的生育力丧失。我们的研究目的是确定 Setd1b、Setdb1、Setd2 和 Cxxc1（编码 CFP1 蛋白）基因在从青春期前到老年后期的新生小鼠卵巢中的时空分布和相对表达水平。为此，我们根据其生殖期和组织学结构创建了五个组：青春期前（3 周龄；n=6）、青春期（7 周龄；n=7）、青春期后（18 周龄；n=7）、早老期（52 周龄；n=7）和晚老期（60 周龄；n=7）。我们发现，Setd1b、Setdb1、Setd2 和 Cxxc1mRNA 水平在新生卵巢组之间存在显著变化（P<0.05）。此外，SETD1B、SETDB1、SETD2 和 CFP1 蛋白在卵巢细胞中的不同亚细胞定位中表现出不同的表达，包括卵母细胞、颗粒细胞、基质和生殖上皮细胞。一般来说，在老年组中，与其他组相比，卵泡、卵母细胞和颗粒细胞以及生殖上皮和基质细胞中的这些蛋白水平显著降低（P<0.05）。这些减少与不同阶段卵泡数量的减少以及老年组黄体结构的减少一致（P<0.05）。总之，这些发现表明，卵巢细胞中组蛋白甲基转移酶基因的表达改变可能与母体年龄增长导致的女性生育力丧失有关。
