Role of Oocyte Loss in Ovarian Surface Mesothelial Cell Transformation
Annual rept. 1 Oct 2001-1 Oct 2002
MASSACHUSETTS GENERAL HOSPITAL BOSTON
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Three Specific Aims SA were proposed to test in mice the hypothesis that accelerated oocyte loss caused by Bclw deficiency or Bax gain-of-function drives ovarian surface mesothelial cell OSMC transformation 1 characterize preneoplastic changes in OSMC of between mice with increasing age 2 determine if disruption of the gene encoding Bax, a Bclw interacting partner required for oocyte apoptosis, rescues the compromised oocyte survival and the OSMC transformation phenotype observed in aging bclw mice and 3 test if targeting overexpression of bax to only growing oocytes accelerates oocyte depletion and causes OSMC transformation To date we have generated the mice needed to complete SA 1 and 2, and have confirmed the occurrence of OSMC transformation in 9 month bclw mutants SA 1 However, there is no evidence of progression to invasive carcinoma by 20 months of age SA 1 We have confirmed that simultaneous inactivation of bax restores the compromised oocyte endowment in bclw mutants to normal SA 2 Finally, we have constructed the zp3-bax minigene and have begun to generate transgenic mice expressing Bax only in growing oocytes SA 3 1 and have shown in another mouse model that accelerated oocyte loss is directly involved in ovarian tumorigenesis.
- Medicine and Medical Research