During decidualization, cells of the endometrium grow and differentiate giving rise to two different decidual tissues located in either the antimesometrial or mesometrial site of the uterus in the rat. These tissues have different functions in pregnancy. The antimesometrial decidua is an endocrine gland that secretes hormones, whereas the mesometrial decidua appears to play an important role in limiting trophoblast invasion. Since the decidual tissue of the rat produces alpha-2-macroglobulin (alpha-2MG), we examined whether this potent protease inhibitor is specifically expressed by the mesometrial tissue, the site of trophoblast invasion, and whether the alpha-2MG gene is regulated by decidual luteotropin (DLt), the PRL-like hormone secreted by the neighboring antimesometrial cells. To determine the secretory proteins of the rat decidua, antimesometrial and mesometrial tissues were dissected out from pseudopregnant rats and cultured with [S-35]methionine. The major protein secreted by the antimesometrial cell was the 29-kilodalton decidual luteotropin, whereas a 180-kilodalton protein was predominantly secreted hy the mesometrial tissue. Immunoprecipitation studies of S-35-radiolabeled proteins revealed that this high mol wt protein is alpha-2MG and that it is secreted exclusively by the cells forming the mesometrial tissue. To examine whether the alpha-2MG gene was also expressed specifically in the mesometrial decidua, total RNA was isolated from both mesometrial and antimesometrial tissues of day 9-12 pseudopregnant rats and hybridized with alpha-2MG cDNA. Northern blot analysis revealed a 5.4-kilobase message, which was abundantly expressed in the mesometrial decidua. Little, if any, alpha-2MG mRNA was detected in antimesometrial decidua. The ontogeny of the message in the decidua correlated well with the development of the mesometrial tissue. To examine whether alpha-2MG expression is regulated by DLt and/or PRL, a highly specific polyclonal antibody to DLt was generated and decidual tissues were cultured in the presence or absence of DLt antibodies with or without PRL. Neutralization of DLt caused a marked decrease in alpha-2MG mRNA levels. This down-regulation was totally reversed by the addition of PRL and was not affected by alpha-2MG antibodies. In summary, the results of this investigation revealed a compartmentalized gene expression, synthesis and secretion Of alpha-2MG in the decidua. The secretion of this protease inhibitor, specifically by the mesometrial tissue which is the site of trophoblast invasion, may be the reason for the minimal amount of tissue damage that occurs during placentation. The results also revealed an up-regulation of mesometrial decidua-specific alpha-2MG by antimesometrial decidua-derived DLt, indicating that in addition to its endocrine role, DLt also acts locally through a paracrine mechanism to maintain an appropriate microenvironment for normal placentation during pregnancy.
