This work is in partial fulfillment of the requirements for the Ph.D. degree of Marat Gorivodsky from the Sackler School of Medicine at Tel Aviv University.
TGFβ2 mRNA Expression and Pregnancy Failure in Mice*
Article first published online: 6 SEP 2011
American Journal of Reproductive Immunology
Volume 42, Issue 2, pages 124–133, August 1999
How to Cite
Gorivodsky, M., Torchinsky, A., Zemliak, I., Savion, S., Fein, A. and Toder, V. (1999), TGFβ2 mRNA Expression and Pregnancy Failure in Mice. American Journal of Reproductive Immunology, 42: 124–133. doi: 10.1111/j.1600-0897.1999.tb00476.x
- Issue published online: 6 SEP 2011
- Article first published online: 6 SEP 2011
- Accepted December 2, 1998
- postimplantation pregnancy loss;
PROBLEM: We describe here a pattern of transforming growth factor (TGF) β2 mRNA expression at the fetomaternal interface in mice with high rate of resorptions as well as its expression following maternal immunopotentiation.
METHOD OF STUDY: TGFβ2 mRNA expression was evaluated in the uteroplacental units of mice with spontaneous (CBA/J × DBA/2J mouse combination) or cyclophosphamide (CP)-induced pregnancy loss. The effect of immunopotentiation on TGFβ2 mRNA expression was determined in CP-treated females who underwent nonspecific immunostimulation with xenogeneic (rat) leukocytes. A quantitative analysis of TGFβ2 mRNA level was performed using RNase protection assay. Distribution of TGFβ2 mRNA transcipts at the fetomaternal interface was studied by in situ hybridization analysis.
RESULTS: RNase protection analysis revealed four TGFβ2 specific mRNA forms (330, 270, 230, and 170 bp) in the uteroplacental units of mice with either normal or decreased reproductive performance. A significant decrease (about 50%) in the level of TGFβ2 mRNA was registered in the uteroplacental unit of mice with pregnancy loss as compared to the control mice. TGFβ2 transcripts were abundant in the uterine epithelium and stroma. A specific hybridization signal was detected also in metrial gland cells and it was found to be substantially lower in CP-treated as compared to intact mice. In the resorbing uteroplacental unit, the expression of TGFβ2 mRNA was completely lost in the uterine epithelium, and the number of TGFβ2 mRNA-positive metrial gland cells was lower as compared to the control. Immunopotentiation decreased the resorption rate in mice with CP-induced pregnancy loss and caused a dramatic increase in TGFβ2 mRNA expression: the level of TGFβ2 mRNA was found to be higher by 2.0–3.2 fold in the uteroplacental unit of immunized as compared to nonimmunized CP-treated mice.
CONCLUSIONS: These data suggest that distortion of TGFβ2 expression at the fetomaternal interface may be associated with pregnancy failure. It seems that beneficial effect of maternal immunostimulation may at least partly be due to the strong increase in TGFβ2 mRNA expression at the fetomaternal interface.