Granulosal cells form highly specialized membrane connections with the oocyte and each other, allowing the passage of regulatory molecules and metabolites between cells. Gene expression changes in granulosal cells may adversely affect oocyte competence resulting in early embryonic loss. The present study was conducted to analyze global gene expression profiles in granulosal cells from persistent ovarian follicles in cows. Cows were assigned randomly to two groups: growing follicles on day 8 and persistent follicles on day 15 of the estrous cycle (estrus=day 0). Cows in the persistent follicle group received progesterone from CIDR-B devices on days 4 through 13. Granulosal cells were collected from both growing and persistent follicles and used in a direct comparison microarray experiment using a bovine long oligo array representing approximately 8400 known genes. Analysis of the microarray data revealed up-regulation of 272 genes (M-value>or=0.9) and down-regulation of 203 genes (M-value<or=-0.9) in granulosal cells from persistent follicles in comparison to growing follicles. Grouping of these genes into themes revealed altered expression of many genes involved in energy and protein metabolism, amino acid transport and apoptosis in granulosal cells of persistent follicles. These data suggest that aged granulosal cells may have a reduced capacity to provide energy and amino acids to the oocyte.