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首页> 外文期刊>Current Biology: CB >Evidence that Meiotic Sex Chromosome Inactivation Is Essential for Male Fertility
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Evidence that Meiotic Sex Chromosome Inactivation Is Essential for Male Fertility

机译：减数分裂性染色体失活对男性生育必不可少的证据

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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) [1]. 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(-/-), H3afx(-/-), Sycp1(-/-), and Msh5(-/-) [2, 3]. However, these also harbor defects in synapsis and/or recombination and as such may activate a putative pachytene checkpoint [4]. 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 [5]. 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 Zfy1/2 paralogs in XY males is sufficient to phenocopy the pachytene arrest phenotype; insertion of Zfy1/2 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.
机译：哺乳动物的X和Y染色体几乎没有同源性，并且在正常减数分裂过程中基本上没有突触。这种突触触发X和Y连锁基因的失活，或减数分裂性染色体失活（MSCI）[1]。尚不清楚MSCI是否对男性减数分裂至关重要。在其中MSCI失败的小鼠突变体中观察到粗线拘捕和凋亡，例如Br​​ca1（-/-），H3afx（-/-），Sycp1（-/-）和Msh5（-/-）[2，3]。然而，这些在突触和/或重组中也存在缺陷，因此可能会激活假定的粗线检查点[4]。在这里，我们提供了MSCI失败足以引起粗线停滞的证据。 XYY雄性表现出Y-Y突触和Y染色体从MSCI逃逸而没有伴随的突触/重组缺陷[5]。我们发现XYY男性，如突触/重组突变体，显示粗线逮捕，这可以通过防止Y-Y突触和相关的Y基因表达来规避。在常染色体上作为转基因插入的单个Y基因的粗线表达表明，在XY雄性中Zfy1 / 2旁系同源物的表达足以表型化粗线逮捕的表型。 Zfy1 / 2插入MSCI的X染色体上会阻止这种反应。我们的发现表明，MSCI对于雄性减数分裂必不可少，因此，可以深入了解减数分裂突变对男性和女性减数分裂作用的不同严重性。

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