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

Amira Sallem; Anne-Lyse Denizot; Ahmed Ziyyat; Audrey L'Hostis; Sophie Favier; Philippe Burlet; Jean-Michel Lapierre; Solohaja Faniaha Dimby; Catherine Patrat; Christophe Sifer; Eric Vicaut; Julie Steffann; Daniel Vaiman; Serge Pierrick Romana; Jean-Philippe Wolf

doi:10.1016/j.xfss.2021.10.004

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

F S Sci. 2022 Feb;3(1):21-28. doi: 10.1016/j.xfss.2021.10.004. Epub 2021 Nov 3.

Authors

Affiliations

¹ Team "From Gametes to Birth," Département Développement, Reproduction, Cancer, Institut Cochin, Institut de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique UMR8104, Université de Paris, 22 rue Mechain, Paris, France; Laboratoire d'Histologie-Embryologie et Cytogénétique, Faculté de Médecine de Monastir, Tunisie.
² Team "From Gametes to Birth," Département Développement, Reproduction, Cancer, Institut Cochin, Institut de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique UMR8104, Université de Paris, 22 rue Mechain, Paris, France; Service d'Histologie-Embryologie-Biologie de la Reproduction, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
³ Team "From Gametes to Birth," Département Développement, Reproduction, Cancer, Institut Cochin, Institut de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique UMR8104, Université de Paris, 22 rue Mechain, Paris, France.
⁴ Service de Génétique Moléculaire, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁶ Unité de Recherche Clinique, ACTION Study Group, Hôpital Fernand Widal, Assistance Publique-Hôpitaux de Paris, Paris, France; Statistique, Analyse et Modélisation Multidisciplinaire-EA 4543, Université Paris 1 Panthéon Sorbonne, Paris, France.
⁷ Service d'Histologie-Embryologie-Cytogénétique-Centre d'Etude et de Conservation des Œufs et du Sperme humains, Centre Hospitalo-Universitaire Jean Verdier, Assistance Publique-Hôpitaux de Paris, Bondy, France.
⁸ Unité de Recherche Clinique, ACTION Study Group, Hôpital Fernand Widal, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁹ Service de Génétique Moléculaire, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut Imagine, Université de Paris, Laboratoire des Maladies Génétiques Mitochondriales. Inserm 1163, Paris, France.
¹⁰ Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Institut Imagine, Université de Paris, Laboratoire d'Embryologie et de Génétique des Malformations Congénitales, Institut de la Santé et de la Recherche Médicale 1163, Paris, France.
¹¹ Team "From Gametes to Birth," Département Développement, Reproduction, Cancer, Institut Cochin, Institut de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique UMR8104, Université de Paris, 22 rue Mechain, Paris, France; Service d'Histologie-Embryologie-Biologie de la Reproduction, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address: jean-philippe.wolf@aphp.fr.

PMID: 35559993
DOI: 10.1016/j.xfss.2021.10.004

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.

Publication types

Randomized Controlled Trial

MeSH terms

Aneuploidy
Comparative Genomic Hybridization
Fertilins / metabolism
Humans
Oocytes*
Peptides / metabolism
Ploidies*

Substances

Peptides
Fertilins