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The loss of global DNA methylation due to decreased DNMT expression in the postnatal mouse ovaries may associate with infertility emerging during ovarian aging.
Histochemistry and Cell Biology ( IF 2.1 ) Pub Date : 2020-06-08 , DOI: 10.1007/s00418-020-01890-w
Fatma Uysal 1, 2 , Saffet Ozturk 1
Affiliation  

Ovarian aging is one of the main causes of female infertility, and its molecular background is still largely unknown. As DNA methylation regulates many oogenesis/folliculogenesis-related genes, the expression levels and cellular localizations of DNA methyltransferases (DNMTs) playing key roles in this process is important in the ovaries from early to aged terms. In the present study, we aimed to evaluate the spatial and temporal expression of the Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3l genes as well as global DNA methylation levels in the mouse ovaries during aging. For this purpose, the following groups were created: young (1- and 2-week old; n = 3 from each week), prepubertal (3- and 4-week-old; n = 3 from each week), pubertal (5- and 6-week-old; n = 3 from each week), postpubertal (16- and 18-week-old; n = 3 from each week), and aged (52-, 60- and 72-week-old; n = 3 from each week). We found here that Dnmt1, Dnmt3a, and Dnmt3l genes’ expression at mRNA and protein levels as well as global DNA methylation profiles were gradually and significantly decreased in the postnatal ovaries from young to aged groups (P < 0.05). In contrast, there was a remarkable increase of Dnmt3b expression in the pubertal, postpubertal and aged groups (P < 0.05). Our findings suggest that the significantly altered DNMT expression and global DNA methylation levels during ovarian aging may contribute to female infertility development at the later terms of lifespan. Also, new researches are required to determine the molecular biological mechanism(s) that how altered DNMT expression and decreased DNA methylation lead to ovarian aging.



中文翻译:


由于出生后小鼠卵巢中 DNMT 表达减少而导致的整体 DNA 甲基化丧失可能与卵巢衰老过程中出现的不孕症有关。



卵巢衰老是女性不孕的主要原因之一,其分子背景仍很大程度上未知。由于 DNA 甲基化调节许多卵子发生/卵泡发生相关基因,因此在此过程中发挥关键作用的 DNA 甲基转移酶 (DNMT) 的表达水平和细胞定位对于从早期到老年的卵巢都很重要。在本研究中,我们旨在评估衰老过程中小鼠卵巢中Dnmt1Dnmt3aDnmt3bDnmt3l基因的空间和时间表达以及总体 DNA 甲基化水平。为此,创建了以下组:青年组(1 周龄和 2 周龄;每周n = 3 名)、青春期前组(3 周龄和 4 周龄;每周n = 3 名)、青春期组(每周 5 名) - 和 6 周龄;每周n = 3 名)、青春期后(16 周和 18 周龄;每周n = 3 名)和老年(52 周、60 周和 72 周;每周n = 3)。我们发现,从年轻组到老年组,出生后卵巢中Dnmt1Dnmt3aDnmt3l基因的 mRNA 和蛋白水平表达以及整体 DNA 甲基化谱逐渐显着降低( P < 0.05)。相比之下,青春期、青春期后和老年组Dnmt3b表达量显着增加( P < 0.05)。我们的研究结果表明,卵巢衰老过程中 DNMT 表达和整体 DNA 甲基化水平的显着改变可能会导致女性在生命后期出现不孕症。 此外,还需要进行新的研究来确定 DNMT 表达改变和 DNA 甲基化减少如何导致卵巢衰老的分子生物学机制。

更新日期:2020-06-08
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