Open AccessPATL 2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice
Author(s) -
ChristouKent Marie,
Kherraf ZineEddine,
AmiriYekta Amir,
Le Blévec Emilie,
Karaouzène Thomas,
Conne Béatrice,
Escoffier Jessica,
Assou Said,
Guttin Audrey,
Lambert Emeline,
Martinez Guillaume,
Boguenet Magalie,
Fourati Ben Mustapha Selima,
Cedrin Durnerin Isabelle,
Halouani Lazhar,
Marrakchi Ouafi,
Makni Mounir,
Latrous Habib,
Kharouf Mahmoud,
Coutton Charles,
ThierryMieg Nicolas,
Nef Serge,
Bottari Serge P,
Zouari Raoudha,
Issartel Jean Paul,
Ray Pierre F,
Arnoult Christophe
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708515
Subject(s) - infertility , epigenetics , medicine , library science , gynecology , genetics , biology , pregnancy , computer science , gene
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 PATL 2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects, respectively. PATL 2'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, PATL 2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.