Format

Send to

Choose Destination
EMBO Mol Med. 2018 Apr 16. pii: e8515. doi: 10.15252/emmm.201708515. [Epub ahead of print]

PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice.

Author information

1
Genetics, Epigenetics and Therapies of Infertility, Institute for Advanced Biosciences, Inserm U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.
2
UM GI-DPI, CHU de Grenoble, Grenoble, France.
3
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
4
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
5
IRMB, INSERM U1183, CHRU Montpellier, Université Montpellier, Montpellier, France.
6
Grenoble Neuroscience Institute, INSERM 1216, Université Grenoble Alpes, Grenoble, France.
7
UM de Génétique Chromosomique, CHU de Grenoble, Grenoble, France.
8
Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia.
9
Service de Médecine de la Reproduction, Centre Hospitalier Universitaire Jean Verdier, Assistance Publique - Hôpitaux de Paris, Bondy, France.
10
Univ. Grenoble Alpes/CNRS, TIMC-IMAG CNRS UMR 5525, Grenoble, France.
11
Genetics, Epigenetics and Therapies of Infertility, Institute for Advanced Biosciences, Inserm U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France christophe.arnoult@univ-grenoble-alpes.fr.

Abstract

The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects, respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA regulators) suggest an original role for Patl2 in mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2-/- animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.

KEYWORDS:

Patl2; female sterility; oocyte developmental competence; oocyte maturation arrest; oocyte maturation failure

PMID:
29661911
DOI:
10.15252/emmm.201708515
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center