EMBO Molecular Medicine (May 2018)
PATL2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice
- Marie Christou‐Kent,
- Zine‐Eddine Kherraf,
- Amir Amiri‐Yekta,
- Emilie Le Blévec,
- Thomas Karaouzène,
- Béatrice Conne,
- Jessica Escoffier,
- Said Assou,
- Audrey Guttin,
- Emeline Lambert,
- Guillaume Martinez,
- Magalie Boguenet,
- Selima Fourati Ben Mustapha,
- Isabelle Cedrin Durnerin,
- Lazhar Halouani,
- Ouafi Marrakchi,
- Mounir Makni,
- Habib Latrous,
- Mahmoud Kharouf,
- Charles Coutton,
- Nicolas Thierry‐Mieg,
- Serge Nef,
- Serge P Bottari,
- Raoudha Zouari,
- Jean Paul Issartel,
- Pierre F Ray,
- Christophe Arnoult
Affiliations
- Marie Christou‐Kent
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Zine‐Eddine Kherraf
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Amir Amiri‐Yekta
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Emilie Le Blévec
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Thomas Karaouzène
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Béatrice Conne
- Department of Genetic Medicine and Development University of Geneva Medical School Geneva Switzerland
- Jessica Escoffier
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Said Assou
- IRMB INSERM U1183 CHRU Montpellier Université Montpellier Montpellier France
- Audrey Guttin
- Grenoble Neuroscience Institute INSERM 1216 Université Grenoble Alpes Grenoble France
- Emeline Lambert
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Guillaume Martinez
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Magalie Boguenet
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Selima Fourati Ben Mustapha
- Polyclinique les Jasmins Centre d'Aide Médicale à la Procréation Centre Urbain Nord Tunis Tunisia
- Isabelle Cedrin Durnerin
- Service de Médecine de la Reproduction Centre Hospitalier Universitaire Jean Verdier Assistance Publique ‐ Hôpitaux de Paris Bondy France
- Lazhar Halouani
- Polyclinique les Jasmins Centre d'Aide Médicale à la Procréation Centre Urbain Nord Tunis Tunisia
- Ouafi Marrakchi
- Polyclinique les Jasmins Centre d'Aide Médicale à la Procréation Centre Urbain Nord Tunis Tunisia
- Mounir Makni
- Polyclinique les Jasmins Centre d'Aide Médicale à la Procréation Centre Urbain Nord Tunis Tunisia
- Habib Latrous
- Polyclinique les Jasmins Centre d'Aide Médicale à la Procréation Centre Urbain Nord Tunis Tunisia
- Mahmoud Kharouf
- Polyclinique les Jasmins Centre d'Aide Médicale à la Procréation Centre Urbain Nord Tunis Tunisia
- Charles Coutton
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Nicolas Thierry‐Mieg
- Univ. Grenoble Alpes/CNRS, TIMC‐IMAG CNRS UMR 5525 Grenoble France
- Serge Nef
- Department of Genetic Medicine and Development University of Geneva Medical School Geneva Switzerland
- Serge P Bottari
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Raoudha Zouari
- Polyclinique les Jasmins Centre d'Aide Médicale à la Procréation Centre Urbain Nord Tunis Tunisia
- Jean Paul Issartel
- Grenoble Neuroscience Institute INSERM 1216 Université Grenoble Alpes Grenoble France
- Pierre F Ray
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- Christophe Arnoult
- Genetics, Epigenetics and Therapies of Infertility Institute for Advanced Biosciences Inserm U1209 CNRS UMR 5309 Université Grenoble Alpes Grenoble France
- DOI
- https://doi.org/10.15252/emmm.201708515
- Journal volume & issue
-
Vol. 10,
no. 5
pp. n/a – n/a
Abstract
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
- female sterility
- oocyte developmental competence
- oocyte maturation arrest
- oocyte maturation failure
- Patl2