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Paul Burgoyne group project:

Further studies of the causes of XYY male infertility

During the pachytene stage of male meiotic prophase the sex chromosomes become transcriptionally silenced (meiotic sex chromosome inactivation; MSCI) and are sequestered in a specialised chromatin domain termed the XY- or sex-body. We have shown that this silencing is due to a meiotic surveillance mechanism that silences the chromatin associated with chromosome axes that have not achieved full synapsis on reaching the pachytene stage. X and Y synapsis is mediated by their terminal pseudoautosomal regions (PARs) and much of the X and Y chromosomal axes remain unsynapsed thus triggering the silencing. However, in XYY males a proportion of pachytene spermatocytes achieve YY synapsis and thus the Y chromosomes escape the silencing. These spermatocytes are selectively eliminated by apoptosis during mid pachytene and we have presumed this is a consequence of ‘inappropriate’ Y gene expression.

In a collaborative study with the Turner group of our Y transgenic lines we have shown that just two genes from the Y short arm when expressed in pachytene cells of normal males lead to mid pachytene apoptosis.

Selected publications

Turner, JMA; Mahadevaiah, SK; Ellis, PJI; Mitchell, MJ and Burgoyne, PS (2006)
Pachytene asynapsis drives meiotic sex chromosome inactivation and leads to substantial postmeiotic repression in spermatids.
Developmental Cell 10, 521-529 PubMed abstract
Turner, JMA; Mahadevaiah, SK; Fernandez-Capetillo, O; Nussenzweig, A; Xu, X; Deng, CX and Burgoyne, PS (2005)
Silencing of unsynapsed meiotic chromosomes in the mouse.
Nature Genetics 37, 41-47 PubMed abstract