MRC National Institute for Medical Research, London
Science for Health
Paul Burgoyne group project:
The causes of XY female infertility
In 1985 we established that XO females have increased perinatal oocyte atresia leading to a reduction of the oocyte pool by half; we have in the past viewed this as a response to the presence of the asynapsed X per se, or to a pachytene checkpoint response to the presence of unrepaired DSBs on the X chromosome. Once again, our discovery of the MSUC response has necessitated a reappraisal. During the pachytene stage (which occurs prenatally) the univalent X remains unsynapsed and is subject to MSUC, or self synapses to form a 'hairpin' structure in which case it escapes silencing. Since the X chromosome carries many genes essential for cell survival, the silencing of the X chromosome in those cells with an unsynapsed X provides a sufficient explanation for the increased oocyte atresia.
XY females also have increased prenatal or perinatal oocyte loss, such that immediately after birth XY and XO females have similar numbers of surviving oocytes. Since these females have a high frequency of X-Y asynapsis this perinatal atresia may also be due to silencing of the unsynapsed X. However, whereas XO females breed reasonably well, most XY females are sterile or nearly so. XYd1 females, that have a deletion of most copies of the Rbmy gene family, are exceptional in that they are regularly fertile. This suggested that Rbmy gene function is in some way deleterious for oocyte survival and consistent with this, we found that this normally testis-specific gene is expressed in the ovaries of XY females.
Selected publications
- Burgoyne PS, Baker TG.
633-45 (1985)
Perinatal oocyte loss in XO mice and its implications for the aetiology of gonadal dysgenesis in XO women.
J Reprod Fertil 75, 633-45 PubMed abstract - Mahadevaiah SK, Odorisio T, Elliott DJ, Rattigan A, Szot M, Laval SH, Washburn LL, McCarrey JR, Cattanach BM, Lovell-Badge R, Burgoyne PS. (1998)
Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities.
Hum Mol Genet. 7, 715-27 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
Burgoyne group
Recent publications
Research projects
- The role of Sly in sex chromosome repression and sperm development
- A Y short arm gene required for the apoptotic response to sex chromosome univalence
- A Y short arm gene required for sperm head elongation and formation of the sperm tail
- X-attached-Y/O males and the MI checkpoint response to univalent sex chromosomes
- Further studies of the causes of XYY male infertility
- The causes of XY female infertility
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