Luteal cell death plays a key role in the regulation of the reproductive process in all mammals. It is also known that prostaglandin (PG) F_2α is one of the main factors that cause luteal demise; still, the effects of PGF_2α on luteal gene transcription have not been fully explored. Using microarray and reverse transcription-polymerase chain reaction, we have profiled gene expression in the corpus luteum (CL) of wild-type and PGF_2α receptor knockout mice on Day 19 of pregnancy. Western blot analysis of selected genes was also performed. Because luteolysis has been shown to be associated with increased oxygen radical production and decreased progesterone synthesis, we report here changes observed in the expression of antioxidant and steroidogenic genes. We found that luteal cells express all genes necessary for progesterone synthesis, whether or not they had undergone luteolysis; however, an increase in mRNA levels of enzymes involved in androgen production, along with a decrease in the expression of enzymes implicated in estrogen synthesis, was observed. We also identified six genes committed to the elimination of free radical species that are dramatically down-regulated in the CL of wild-type animals with respect to PGF_2α receptor knockout mice. Similar changes in the expression of steroidogenic and antioxidant genes were found in the CL of wild-type animals between Days 15 and 19 of pregnancy. It is proposed that an increase in the androgen:estrogen biosynthesis ratio, along with a significantly reduced expression of free radical scavenger proteins, may play an important role in the luteolytic process.