TGF beta 2 mRNA expression and pregnancy failure in mice

PROBLEM: We describe here a pattern of transforming growth factor (TGF) bet a 2 mRNA expression at the fetomaternal interface in mice with high rate of resorptions as well as its expression following maternal immunopotentiatio n. METHOD OF STUDY: TGF beta 2 mRNA expression was evaluated in the uteroplace ntal units of mice with spontaneous (CBA/J x DBA/2J mouse combination) or c yclophosphamide (CP)-induced pregnancy loss. The effect of immunopotentiati on on TGF beta 2 mRNA expression was determined in CP-treated females who u nderwent nonspecific immunostimulation with xenogeneic (rat) leukocytes. A quantitative analysis of TGF beta 2 mRNA level was performed using RNase pr otection assay. Distribution of TGF beta 2 mRNA transcipts at the felomater nal interface was studied by in situ hybridization analysis. RESULTS: RNase protection analysis revealed four TGF beta 2 specific mRNA f orms (330, 270, 230, and 170 bp) in the uteroplacental units of mice with e ither normal or decreased reproductive performance. A significant decrease (about 50%) in the level of TGF beta 2 mRNA was registered in the uteroplac ental unit of mice with pregnancy loss as compared to the control mice. TGF beta 2 transcripts were abundant in the uterine epithelium and stroma. A s pecific hybridization signal was detected also in metrial gland cells and i t was found to be substantially lower in CP-treated as compared to intact m ice. In the resorbing. uteroplacental unit, the expression of TGF beta 2 mR NA was completely lost in the uterine epithelium. and the number of TGF bet a 2 mRNA-positive metrial gland cells was lower as compared to the control. Immunopotentiation decreased the resorption rate in mice with CP-induced p regnancy loss and caused;I dramatic increase in TGF beta 2 mRNA expression: the level of TGF beta 2 mRNA uas found to be higher by 2.0-3.2 fold in the uteroplacental unit of immunized as compared to nonimmunized CP-treated mi ce. CONCLUSIONS: These data suggest that distortion of TGF beta 2 expression at the fetomaternal interface may be associated with pregnancy failure. It st ems that beneficial effect of maternal immunostimulation may at least partl y be due to the strong increase in TGF beta 2 mRNA expression at the fetoma ternal interface.