title: Mammalian meiotic silencing exhibits sexually dimorphic features.
abstract: During mammalian meiotic prophase I, surveillance mechanisms exist to ensure that germ cells with defective synapsis or recombination are eliminated, thereby preventing the generation of aneuploid gametes and embryos. Meiosis in females is more error-prone than in males, and this is in part because the prophase I surveillance mechanisms are less efficient in females. A mechanistic understanding of this sexual dimorphism is currently lacking. In both sexes, asynapsed chromosomes are transcriptionally inactivated by ATR-dependent phosphorylation of histone H2AFX. This process, termed meiotic silencing, has been proposed to perform an important prophase I surveillance role. While the transcriptional effects of meiotic silencing at individual genes are well described in the male germ line, analogous studies in the female germ line have not been performed. Here we apply single- and multigene RNA fluorescence in situ hybridization (RNA FISH) to oocytes from chromosomally abnormal mouse models to uncover potential sex differences in the silencing response. Notably, we find that meiotic silencing in females is less efficient than in males. Within individual oocytes, genes located on the same asynapsed chromosome are silenced to differing extents, thereby generating mosaicism in gene expression profiles across oocyte populations. Analysis of sex-reversed XY female mice reveals that the sexual dimorphism in silencing is determined by gonadal sex rather than sex chromosome constitution. We propose that sex differences in meiotic silencing impact on the sexually dimorphic prophase I response to asynapsis.
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Cloutier
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Mahadevaiah
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
authors.forename: E
authors.initials: E
authors.lastname: ElInati
authors.affiliation: Institute of Physiological Chemistry, Technische Universität Dresden, Dresden, 01307, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Tóth
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, NW7 1AA, UK. James.Turner@crick.ac.uk.
authors.forename: James
authors.initials: J
authors.lastname: Turner
mesh_terms: D000818:Animals; D005260:Female; D020868:Gene Silencing; D005854:Germ Cells / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis; D051379:Mice / Q000235:genetics* / Q000502:physiology; D012727:Sex Characteristics; D012730:Sex Chromosomes / Q000235:genetics* / Q000378:metabolism
keywords: Checkpoints; Epigenetics; Meiosis; Meiotic silencing; Oocytes; Sex differences