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Changes in the Expression of Steroidogenic and Antioxidant Genes in the Mouse Corpus Luteum During Luteolysis¹

Department of Obstetrics, Gynecology, and Reproductive Science,³ Yale University School of Medicine, New Haven, Connecticut 06520 Department of Physiological Chemistry,⁴ Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan

Luteal cell death plays a key role in the regulation of the reproductive process in all mammals. It is also known that prostaglandin (PG) F₂ is one of the main factors that cause luteal demise; still, the effects of PGF₂ 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 PGF₂ 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 PGF₂ 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.

corpus luteum function, female reproductive tract, ovary, pregnancy

² Correspondence: Carlos Stocco, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208063, New Haven, CT 06520. FAX: 203 785 7134; carlos.stocco{at}yale.edu

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