TGF beta 2 mRNA expression and pregnancy failure in mice.
OBJECTIVE
We describe here a pattern of transforming growth factor (TGF) beta2 mRNA expression at the fetomaternal interface in mice with high rate of resorptions as well as its expression following maternal immunopotentiation.


METHODS
TGF beta 2 mRNA expression was evaluated in the uteroplacental units of mice with spontaneous (CBA/J x DBA/2J mouse combination) or cyclophosphamide (CP)-induced pregnancy loss. The effect of immunopotentiation on TGF beta 2 mRNA expression was determined in CP-treated females who underwent nonspecific immunostimulation with xenogeneic (rat) leukocytes. A quantitative analysis of TGF beta 2 mRNA level was performed using RNase protection assay. Distribution of TGF beta 2 mRNA transcripts at the fetomaternal interface was studied by in situ hybridization analysis.


RESULTS
RNase protection analysis revealed four TGF beta 2 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 TGF beta 2 mRNA was registered in the uteroplacental 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 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 TGF beta 2 mRNA was completely lost in the uterine epithelium, and the number of TGF beta 2 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 TGF beta 2 mRNA expression: the level of TGF beta 2 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 TGF beta 2 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 TGF beta 2 mRNA expression at the fetomaternal interface.
Gorivodsky
M
M
Department of Embryology and Teratology, Sackler School of Medicine, Tel Aviv University, Israel.
Torchinsky
A
A
Zemliak
I
I
Savion
S
S
Fein
A
A
Toder
V
V
D000028:Abortion, Induced; D000022:Abortion, Spontaneous / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D020964:Embryo Loss / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D020318:Rats, Long-Evans; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D000276:Adjuvants, Immunologic; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta