Modulation of granulosa cell apoptosis

Abstract

The present invention relates to a method of modulating apoptosis of a granulosa cell. The method includes one or more of the following steps: (i) modulating the concentration and/or activity of BMP-15 and/or BMP-6 that the granulosa cell is exposed to; (ii) modulating activity of a BMP-15 dependent signalling pathway in the granulosa cell; and (iii) modulating activity of a BMP-6 dependent signalling pathway in a granulosa cell.

1 . A medium comprising:
 (a) a growth factor component comprising:
 (i) at least one of epidermal growth factor (EGF), amphiregulin and epiregulin; and 
 (ii) at least one of Growth Differentiation Factor 9 (GDF-9), Bone Morphogenetic Protein 15 (BMP-15) and Bone Morphogenetic Protein 6 (BMP-6); and optionally 
   (b) at least one of the following:
 (i) one or more denuded oocytes; 
 (ii) oocyte-conditioned medium; 
 (iii) one or more oocyte secreted factors; 
 (iv) an agent that increases the activity of a GDF-9-dependent signalling pathway in one or more of an oocyte, a cumulus cell associated with an oocyte, and an embryo; 
 (v) an agent that increases the activity of a BMP-15-dependent signalling pathway in one or more of an oocyte, a cumulus cell associated with an oocyte, and an embryo; and 
 (vi) an agent that increases the activity of a BMP-6-dependent signalling pathway in one or more of an oocyte, a cumulus cell associated with an oocyte, and an embryo, 
   
       wherein the growth factor component supports culture of a cumulus oocyte complex. 
     
     
         2 . A combination product including:
 (a) at least one of epidermal growth factor (EGF), amphiregulin and epiregulin;   (b) at least one of GDF-9, BMP-15 and BMP-6; and   (c) a medium that supports the culture of a cumulus oocyte complex; and optionally   (d) at least one of the following:
 (i) one or more oocyte secreted factors; 
 (ii) oocyte conditioned medium; 
 (iii) an agent that increases the activity of a GDF-9-dependent signalling pathway in one or more of an oocyte, a cumulus cell associated with an oocyte, and an embryo; 
 (iv) an agent that increases the activity of a BMP-15-dependent signalling pathway in one or more of an oocyte, a cumulus cell associated with an oocyte, and an embryo; and 
 (v) an agent that increases the activity of a BMP-6-dependent signalling pathway in one or more of an oocyte, a cumulus cell associated with an oocyte, and an embryo; 
   
       wherein components (a), (b) and (d) are provided in a form for addition to the medium that supports the culture of the cumulus oocyte complex.