PATL 2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice

• DOI: 10.15252/emmm.201708515
• Publication Date: 2018-04-16T10:20:11Z
• Authors: 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 Be...; Isabelle Cedrin D...; 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
• Keywords: Medicine (General); Maneb/adverse effects; QH426-470; Cohort Studies; Models; Lung/drug effects/ultrastructure; oocyte developmental competence; Trachea/drug effects/ultrastructure; ddc:576.5; Scanning; [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis; Research Articles; Fungicides; Mice, Knockout; Microscopy; [SDV.BDD.GAM] Life Sciences [q-bio]/Development Biology/Gametogenesis; 0303 health sciences; Patl2; Nuclear Proteins; RNA-Binding Proteins; Meiosis; Codon, Nonsense; [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]; oocyte maturation failure; Female; Epithelium/drug effects/pathology; female sterility; Adult; 570; Mice, Transgenic; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; Electron; Young Adult; 03 medical and health sciences; R5-920; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]; Exome Sequencing; Genetics; Animals; Humans; Industrial/adverse effects; Columbidae; Molecular Biology/Genomics [q-bio.GN]; info:eu-repo/classification/ddc/576.5; Gene Expression Profiling; Biological; Mice, Inbred C57BL; Zineb/adverse effects; Infertility; Oocytes; oocyte maturation arrest; Sentinel Surveillance; Electron Probe Microanalysis; Environmental Exposure/adverse effects

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.