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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

Rosalia Battaglia1, Paolo Musumeci2, Marco Ragusa1,3, Davide Barbagallo1, Marina Scalia1, Massimo Zimbone4, Josè Maria Lo Faro2,4,5, Placido Borzì6, Paolo Scollo6, Michele Purrello1, Elena Maria Vento6, Cinzia Di Pietro1
  • 1Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy
  • 2Department of Physics and Astronomy, University of Catania, Catania 95123, Italy
  • 3Oasi Research Institue-IRCCS, Troina 94018, Italy
  • 4CNR-IMM, Catania 95123, Italy
  • 5IPCF-CNR, viale F. Messina 98158, Italy
  • 6IVF Unit, Cannizzaro Hospital, Catania 95126, Italy
Received: February 11, 2020Accepted: May 25, 2020Published: June 17, 2020
https://doi.org/10.18632/aging.103441

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.