A fertilin-derived peptide improves in vitro maturation and ploidy of human oocytes

Abstract

Objective: To analyze the effect of a cyclic fertilin-derived peptide (cFEE) on in vitro maturation of human oocytes.

Design: Randomized study.

Setting: Fertility center in an academic hospital.

Patient(s): Not applicable.

Intervention(s): Human immature germinal vesicle-stage oocytes (n = 1,629) donated for research according to French bioethics laws were randomly allocated to groups treated with 1 or 100 μM of cFEE or to a control group. They were incubated at 37 °C in 6% CO₂ and 5% O₂, and their maturation was assessed using time-lapse microscopy over 24 hours. In vitro maturated metaphase II oocytes were analyzed for chromosomal content using microarray comparative genomic hybridization, and their transcriptomes were analyzed using Affymetrix Clariom D microarrays.

Main outcome measure(s): The percentage of oocytes undergoing maturation in vitro was observed. Aneuploidy and euploidy were assessed for all chromosomes, and differential gene expression was analyzed in oocytes treated with cFEE compared with the control to obtain insights into its mechanism of action.

Result(s): cFEE significantly increased the percentage of oocytes that matured in vitro and improved euploidy in meiosis II oocytes by the up-regulation of FMN1 and FLNA genes, both of which encode proteins involved in spindle structure.

Conclusion(s): cFEE improves human oocyte maturation in vitro and reduces aneuploidy. It may prove useful for treating oocytes before fertilization in assisted reproductive technology and for in vitro maturation in fertility preservation programs to improve oocyte quality and the chances for infertile couples to conceive.

Keywords: FLNA; FMN1; Human oocyte; chromosome segregation; invitro maturation.