title: Evidence that meiotic sex chromosome inactivation is essential for male fertility.
abstract: The mammalian X and Y chromosomes share little homology and are largely unsynapsed during normal meiosis. This asynapsis triggers inactivation of X- and Y-linked genes, or meiotic sex chromosome inactivation (MSCI). Whether MSCI is essential for male meiosis is unclear. Pachytene arrest and apoptosis is observed in mouse mutants in which MSCI fails, e.g., Brca1(-/-), H2afx(-/-), Sycp1(-/-), and Msh5(-/-). However, these also harbor defects in synapsis and/or recombination and as such may activate a putative pachytene checkpoint. Here we present evidence that MSCI failure is sufficient to cause pachytene arrest. XYY males exhibit Y-Y synapsis and Y chromosomal escape from MSCI without accompanying synapsis/recombination defects. We find that XYY males, like synapsis/recombination mutants, display pachytene arrest and that this can be circumvented by preventing Y-Y synapsis and associated Y gene expression. Pachytene expression of individual Y genes inserted as transgenes on autosomes shows that expression of the Zfy 1/2 paralogs in XY males is sufficient to phenocopy the pachytene arrest phenotype; insertion of Zfy 1/2 on the X chromosome where they are subject to MSCI prevents this response. Our findings show that MSCI is essential for male meiosis and, as such, provide insight into the differential severity of meiotic mutations' effects on male and female meiosis.
authors.affiliation: Department of Stem Cell Research and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: Hélène
authors.initials: H
authors.lastname: Royo
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Polikiewicz
authors.forename: Shantha K
authors.initials: SK
authors.lastname: Mahadevaiah
authors.forename: Haydn
authors.initials: H
authors.lastname: Prosser
authors.forename: Mike
authors.initials: M
authors.lastname: Mitchell
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.forename: Paul S
authors.initials: PS
authors.lastname: Burgoyne
authors.forename: James M A
authors.initials: JM
authors.lastname: Turner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D023902:Chromosome Pairing; D005260:Female; D005298:Fertility / Q000235:genetics*; D020868:Gene Silencing; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D014960:X Chromosome / Q000235:genetics*; D014998:Y Chromosome / Q000235:genetics*