Research Paper Volume 12, Issue 12 pp 12324—12341
Ovarian aging increases small extracellular vesicle CD81+ release in human follicular fluid and influences miRNA profiles
- 1 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
- 2 Department of Physics and Astronomy, University of Catania, Catania 95123, Italy
- 3 Oasi Research Institue-IRCCS, Troina 94018, Italy
- 4 CNR-IMM, Catania 95123, Italy
- 5 IPCF-CNR, viale F. Messina 98158, Italy
- 6 IVF Unit, Cannizzaro Hospital, Catania 95126, Italy
Received: February 11, 2020 Accepted: May 25, 2020 Published: June 17, 2020
https://doi.org/10.18632/aging.103441How to Cite
Copyright © 2020 Battaglia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.