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Changes in the expression of steroidogenic and antioxidant genes in the mouse corpus luteum during luteolysis Foyouzi N, ET AL .
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(2alpha) is one of the main factors that cause luteal demise; still, the effects of PGF(2alpha) 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(2alpha) 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(2alpha) 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.
The results also showed that the mRNA of all members of the peroxiredoxin (Prdx) family of proteins are expressed in the CL. Prdx1, Prdx2, Prdx3, and Prdx6 mRNA were found to be highly expressed, while Prdx4 and Prdx5 were found to be present at low levels (Fig. 3B, lower). Low relative expression levels of catalase (Cat) were found (Fig. 3, lower). Messenger RNA levels of Prdx6 were significantly lower in wild-type mice compared with PGF2 receptor knockout animals (Fig. 3B, top).
High luteal mRNA levels for glutathione peroxidase (Gpx) types 1, 3, and 4 were found in both wild-type and PGF2 receptor knockout mice (Fig. 3B, lower), and no differences were found in mRNA levels of these enzymes between these two groups (Fig. 3B, top).
It was also found that luteal cells express the mRNA for the -tocopherol transfer protein (Ttpa). Levels of Ttpa mRNA were 10-fold higher in luteal cells of PGF2 receptor knockout mice than in cells of wild-type animals (Fig. 3B). In wild-type mice, a significant decrease in microsomal glutathione S-transferase (Mgst) 2 mRNA levels was found compared with levels in PGF2 receptor knockout mice, but no differences were found in the expression of Mgst1 and Mgst3 (Fig. 3B, top). Mgst1 mRNA was found to be expressed at very high relative levels, whereas Mgst2 and Mgst3 were expressed at moderate and low relative levels, respectively.
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