Ovarian aging increases small extracellular vesicle CD81+ release in human follicular fluid and influences miRNA profiles

Rosalia Battaglia, Paolo Musumeci, Marco Ragusa, Davide Barbagallo, Marina Scalia, Massimo Zimbone, Maria Josè Lo Faro, Placido Borzì, Paolo Scollo, Michele Purrello, Maria Elena Vento, Cinzia Di Pietro

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)12324-12341
Number of pages18
Issue number12
Publication statusPublished - Jun 30 2020


  • Extracellular vesicles
  • Follicular fluid
  • MicroRNAs
  • Reproductive aging

ASJC Scopus subject areas

  • Ageing
  • Cell Biology


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