Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy.
Department of Physics and Astronomy, University of Catania, Catania 95123, Italy.
Aging (Albany NY). 2020 Jun 17;12(12):12324-12341. doi: 10.18632/aging.103441.
Ovarian aging affects female reproductive potential and is characterized by alterations in proteins, mRNAs and non-coding RNAs inside the ovarian follicle. Ovarian somatic cells and the oocyte communicate with each other secreting different molecules into the follicular fluid, by extracellular vesicles. The cargo of follicular fluid vesicles may influence female reproductive ability; accordingly, analysis of extracellular vesicle content could provide information about the quality of the female germ cell.In order to identify the most significant deregulated microRNAs in reproductive aging, we quantified the small extracellular vesicles in human follicular fluid from older and younger women and analyzed the expression of microRNAs enclosed inside the vesicles. We found twice as many small extracellular vesicles in the follicular fluid from older women and several differentially expressed microRNAs. Correlating microRNA expression profiles with vesicle number, we selected 46 deregulated microRNAs associated with aging. Bioinformatic analyses allowed us to identify six miRNAs involved in TP53 signaling pathways. Specifically, miR-16-5p, miR214-3p and miR-449a were downregulated and miR-125b, miR-155-5p and miR-372 were upregulated, influencing vesicle release, oocyte maturation and stress response. We believe that this approach allowed us to identify a battery of microRNAs strictly related to female reproductive aging.
卵巢衰老影响女性生殖潜能，其特征是卵巢卵泡内蛋白质、mRNA 和非编码 RNA 的改变。卵巢体细胞和卵母细胞通过细胞外囊泡相互交流，将不同的分子分泌到卵泡液中。卵泡液囊泡的货物可能会影响女性的生殖能力；因此，分析细胞外囊泡的内容可以提供有关女性生殖细胞质量的信息。为了确定生殖衰老过程中最显著的失调 microRNAs，我们定量分析了来自老年和年轻女性的人卵泡液中的小细胞外囊泡，并分析了囊泡内 microRNAs 的表达。我们发现老年女性卵泡液中的小细胞外囊泡数量增加了一倍，并且存在几种差异表达的 microRNAs。将 microRNA 表达谱与囊泡数量相关联，我们选择了 46 个与衰老相关的失调 microRNAs。生物信息学分析允许我们鉴定出六个参与 TP53 信号通路的 miRNA。具体而言，miR-16-5p、miR214-3p 和 miR-449a 下调，miR-125b、miR-155-5p 和 miR-372 上调，影响囊泡释放、卵母细胞成熟和应激反应。我们相信，这种方法使我们能够鉴定出与女性生殖衰老密切相关的一系列 microRNAs。
