title: Cytokine expression in the uterus of mice with pregnancy loss: effect of maternal immunopotentiation with GM-CSF.
abstract: It is believed that failure of the maternal immune system to actively support embryonic development, through production of the appropriate cytokine network, might be responsible for embryonic death. Thus, the aim of this study was to evaluate the possible involvement of cytokines such as tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta2 (TGF-beta2), which are crucial for normal embryonic development, in the early stages of mechanisms that mediate induced pregnancy loss. The early stages of the resorption process induced by lipopolysaccharide (LPS) were characterized by blood accumulation in the vicinity of the embryo, preceding any visible embryonic damage. At that time, immunohistochemical analysis revealed an increased expression of TNF-alpha in the primary and secondary decidua, which was reduced as the resorption process was completed. In contrast, TGF-beta2 expression was decreased in the primary and secondary decidua, as well as in the glandular epithelium, at all the times assessed. Maternal immunopotentiation with granulocyte macrophage-colony stimulating factor (GM-CSF), which controls maternal immune activities supporting normal embryonic development, decreased the resorption rate in LPS-treated mice while normalizing the expression of TNF-alpha and TGF-beta2 in the uterus of these animals throughout the ongoing resorption process. These results indicate a possible role for maternal immunopotentiation with GM-CSF in the mechanisms mediating the early stages of pregnancy loss, possibly via modulation of TNF-alpha and TGF-beta2 activity.
authors.affiliation: Department of Embryology and Teratology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. shoshans@plato.tau.ac.il
authors.forename: S
authors.initials: S
authors.lastname: Savion
authors.forename: E
authors.initials: E
authors.lastname: Zeldich
authors.forename: H
authors.initials: H
authors.lastname: Orenstein
authors.forename: J
authors.initials: J
authors.lastname: Shepshelovich
authors.forename: A
authors.initials: A
authors.lastname: Torchinsky
authors.forename: H
authors.initials: H
authors.lastname: Carp
authors.forename: V
authors.initials: V
authors.lastname: Toder
authors.forename: A
authors.initials: A
authors.lastname: Fein
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D016207:Cytokines / Q000032:analysis*; D005260:Female; D005865:Gestational Age; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D007150:Immunohistochemistry / Q000379:methods; D008070:Lipopolysaccharides; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014599:Uterus / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor