Enhancement of the efficiency of oocyte vitrification through regulation of histone deacetylase 6 expression

J Assist Reprod Genet. 2018 Jul;35(7):1179-1185. doi: 10.1007/s10815-018-1221-6. Epub 2018 Jul 4.

Abstract

Objective: Successful oocyte vitrification (OV) is critical for cryopreservation of the oocytes from female patients with infertility, polycystic ovaries, and gynecologic cancers. Recent evidence suggests that relatively low levels of histone acetylation are critical for maintenance of the maturation capacity of cryopreserved oocytes. However, previous studies have only demonstrated a key role of histone deacetylases (HDAC) 1 and 2 in the cryopreservation of oocytes.

Methods: In this study, we investigated the role of HDAC6 in these settings. We found that mouse oocytes with low HDAC6 levels decreased survival rate, cleavage rate, and blastocyst rate after OV. Bioinformatics analyses were used to predict HDAC6-targeting microRNAs (miRNAs), while the functional binding of miRNAs to HDAC6 mRNA was evaluated by a dual luciferase reporter assay.

Results: Among all HDAC6-targeting miRNAs, we detected expression of miR-558, miR-527, and miR-762 in mouse oocytes. Specifically, we found that only miR-762 significantly inhibited protein translation of HDAC6 via binding to the 3'-UTR of the HDAC6 mRNA. Transfection of oocytes with HDAC6 or antisense of miR-762 significantly increased the survival rate, the cleavage rate, and blastocyst rate after OV.

Conclusion: As a result, our data suggest that induction of HDAC6 levels by miR-762 suppression may improve the current protocol for OV.

Keywords: Histone deacetylases 6 (HDAC6); Oocyte vitrification (OV); miR-337-3p.

MeSH terms

  • Acetylation
  • Animals
  • Blastocyst / metabolism
  • Blastocyst / physiology
  • Cryopreservation / methods
  • Female
  • Histone Deacetylase 6 / metabolism*
  • In Vitro Oocyte Maturation Techniques / methods
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • Oocytes / metabolism*
  • Oocytes / physiology*
  • Pregnancy
  • RNA, Messenger / genetics
  • Vitrification

Substances

  • MicroRNAs
  • RNA, Messenger
  • Histone Deacetylase 6