Article

Glial cell line-derived neurotrophic factor: an intraovarian factor that enhances oocyte developmental competence in vitro.

Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada.
Endocrinology (impact factor: 4.46). 10/2007; 148(9):4292-301. DOI:10.1210/en.2007-0021
Source: PubMed

ABSTRACT The success of early embryonic development depends on oocyte nuclear and cytoplasmic maturation. We have investigated whether glial cell line-derived neurotrophic factor (GDNF) affects the in vitro maturation (IVM) of porcine oocytes and their subsequent ability to sustain preimplantation embryo development. GDNF and both its coreceptors, GDNF family receptor alpha-1 (GFR alpha-1) and the rearranged during transformation (RET) receptor, were expressed in oocytes and their surrounding cumulus cells derived from small and large follicles. When included in IVM medium, GDNF significantly enhanced cumulus cell expansion of both small and large cumulus-oocyte complexes and increased the percentage of small follicle-derived oocytes maturing to the metaphase II stage, although nuclear maturation of large oocytes was not significantly affected. Examination of cyclin B1 protein expression as a measure of cytoplasmic maturation revealed that in the presence of GDNF, cyclin B1 levels were significantly increased in large follicle-derived oocytes, as well as in oocytes from small follicles to a level comparable to the untreated large group. After activation, a significantly higher percentage of both small and large oocytes that were matured in the presence of GDNF developed to the blastocyst stage compared with untreated controls. Indeed, GDNF enhanced the blastocyst rate of small oocytes to levels comparable to those obtained for large oocytes matured without GDNF. The effect of GDNF was specific; this was evident because its enhancement of nuclear maturation and embryo developmental potential was blocked by an antibody against GFR alpha-1. Our study provides the first functional evidence that GDNF affects oocyte maturation and preimplantation embryo developmental competence in a follicular stage-dependent manner. This finding may provide insights for improving the formulation of IVM culture systems, especially for oocytes from small follicles.

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Keywords

cumulus cell expansion
 
cyclin B1 levels
 
cyclin B1 protein expression
 
embryo developmental potential
 
follicular stage-dependent manner
 
glial cell line-derived neurotrophic factor
 
IVM culture systems
 
large cumulus-oocyte complexes
 
large follicle-derived oocytes
 
large oocytes
 
level comparable
 
levels comparable
 
oocyte nuclear
 
porcine oocytes
 
preimplantation embryo developmental competence
 
small follicle-derived oocytes
 
small oocytes
 
subsequent ability
 
surrounding cumulus cells
 
untreated large group
 

Katja Linher