The murine 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene family: a postulated role for 3beta-HSD VI during early pregnancy.

The enzyme 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) is essential for the biosynthesis of all active steroid hormones. The 3beta-HSD enzyme consists in multiple isoforms, each the product of a distinct gene. In the mouse, six tissue-specific isoforms have been identified. These isoforms are expressed in a tissue- and temporal specific manner. Mouse 3beta-HSD VI is the only isoform expressed in decidua and giant trophoblast cells during the first half of mouse pregnancy. The tissue- and temporal-specific expression of 3beta-HSD VI during mouse pregnancy, as determined by in situ hybridization and immunohistochemistry, shows that 3beta-HSD is expressed exclusively in the antimesometrial decidua on E6.5 and E7.5. By E9.5, expression of 3beta-HSD is observed in giant trophoblast cells with a marked increase in expression by E10.5. No expression of 3beta-HSD is seen in decidua after E7.5 and no expression of 3beta-HSD is seen in the embryo at any of the times investigated. Giant trophoblast cells in culture from E9.5 and E10.5 synthesize progesterone with cells from E10.5 producing about 3.5-fold more progesterone during the first 24 h in culture. Western blot analysis of 3beta-HSD VI protein demonstrates that the amount of 3beta-HSD VI protein correlates with the amount of progesterone biosynthesis in giant trophoblast cells from E9.5 and E10.5. We propose that progesterone produced during the first half of mouse pregnancy in decidua and giant trophoblast cells acts as an immunosuppressant at the fetal maternal interface to prevent rejection of the fetus.

Uterine and placental expression of steroidogenic genes during rodent pregnancy.

The ontogeny and functional role of steroidogenesis during mammalian gestation is poorly understood. This review provides a summary of our recent findings on the spatio-temporal expression of key steroidogenic genes controlling progesterone synthesis in the uterus during mouse pregnancy. We have shown that onset of cholesterol side chain cleavage cytochrome P450 (P450scc) and a newly identified isoform of murine 3beta-hydroxysteroid dehydrogenase/isomerase type VI (3betaHSD VI) expression occurs upon decidualization of the uterine wall induced by implantation. This unexpected early expression of the enzymes in the maternal decidua is terminated at mid-pregnancy when the steroidogenic ability reappears in the extraembryonic giant cells at the time of placentation. The giant cells express another protein indispensable for steroid hormone synthesis in the adrenal and gonads, Steroidogenic Acute Regulatory (StAR) protein. Unlike the human placenta, the steroidogenic genes are not expressed in the cells of the mature mouse placenta during the second half of gestation. Finally, our studies suggest that transcriptional regulation of P450scc is mediated by a non-SF-1 protein that substitutes SF-1 functions in the extraembryonic cells. Collectively, the results of the present study suggest that, during early phases of pregnancy, local progesterone synthesis in the maternal decidua and the trophoblast layers surrounding the embryonal cavity is important for successful implantation and/or maintenance of pregnancy. We propose that the local production of progesterone acts as an immunosuppressant at the maternofetal interface preventing the rejection of the fetal allograft.