title: Extracellular microRNAs in follicular fluid and their potential association with oocyte fertilization and embryo quality: an exploratory study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan and Sackler School of Medicine Tel- Aviv University, Tel Aviv, Israel. Ronit.Machtinger@Sheba.health.gov.il.
authors.forename: Ronit
authors.initials: R
authors.lastname: Machtinger
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Rodosthenis S
authors.initials: RS
authors.lastname: Rodosthenous
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan and Sackler School of Medicine Tel- Aviv University, Tel Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Adir
authors.affiliation: Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan and Sackler School of Medicine Tel- Aviv University, Tel Aviv, Israel.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Mansour
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Racowsky
authors.affiliation: Human Epigenetics Laboratory, Columbia University, Mailman School of Public Health, New York, NY, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Russ
authors.initials: R
authors.lastname: Hauser
mesh_terms: D000328:Adult; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism*
chemical_list: D035683:MicroRNAs
keywords: Exosomes; Extracellular vesicles; Fertilization; Follicular fluid; MicroRNAs; Reproduction