Extracellular microRNAs in follicular fluid and their potential association with oocyte fertilization and embryo quality: an exploratory study

Abstract

Purpose

The purpose of this study is to determine the profile of extracellular microRNAs (exmiRNAs) in follicular fluid (FF) and explore their association with fertilization potential and embryo quality.

Methods

We collected FF from single follicles containing mature oocytes from 40 women undergoing IVF and we screened for the expression of 754 exmiRNAs in FF using the TaqMan OpenArray® qPCR platform. To determine the association of exmiRNAs and IVF outcomes, we compared their expression levels in FF samples that differ by fertilization status (normally, abnormally, and failed to fertilize) and embryo quality (top vs. non-top).

Results

We detected 207 exmiRNAs, of which miR-30d-5p, miR-320b, miR-10b-3p, miR-1291, and miR-720 were most prevalent. We identified four exmiRNAs with significant fold change (FC) when FF that contained normally fertilized was compared to failed to fertilize oocytes [miR-202-5p (FC = 1.82, p = 0.01), miR-206 (FC = 2.09, p = 0.04), miR-16-1-3p (FC = 1.88, p = 0.05), and miR-1244 (FC = 2.72, p = 0.05)]. We also found four exmiRNAs to be significantly differentially expressed in FF that yielded top quality versus non-top quality embryos [(miR-766-3p (FC = 1.95, p = 0.01), miR-663b (FC = 0.18, p = 0.02), miR-132-3p (FC = 2.45, p = 0.05), and miR-16-5p (FC = 3.80, p = 0.05)]. In-silico analysis revealed that several of these exmiRNAs are involved in pathways implicated in reproductive system diseases, organismal abnormalities, and organ development.

Conclusions

Our findings suggest that exmiRNAs in the follicular fluid can lead to downstream events that will affect fertilization and day 3 embryo morphology. We encourage further observational and experimental studies to confirm our findings and to determine the role of exmiRNAs in human reproduction.

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Acknowledgements

We thank the patients that donated the follicular fluid and the IVF team contributing to this study.

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Correspondence to Ronit Machtinger.

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Funding

This study was funded by Grant Award no. RPGA1301 from the Environmental and Health Fund (EHF), Israel and by grants P30ES00002 and R21ES024236 from the National Institute of Environmental Health Sciences, USA.

Additional information

Ronit Machtinger and Rodosthenis S. Rodosthenous contributed equally to this work.

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Machtinger, R., Rodosthenous, R.S., Adir, M. et al. Extracellular microRNAs in follicular fluid and their potential association with oocyte fertilization and embryo quality: an exploratory study. J Assist Reprod Genet 34, 525–533 (2017). https://doi.org/10.1007/s10815-017-0876-8

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Keywords

  • Follicular fluid
  • MicroRNAs
  • Extracellular vesicles
  • Exosomes
  • Fertilization
  • Reproduction