Diabetes teratogenicity is accompanied by alterations in macrophages and T cell subpopulations in the uterus and lymphoid organs.
Insulin-dependent diabetes mellitus is a well-known teratogen, which might cause growth retardation, malformations and fetal death. We have previously shown, that potentiation of the maternal immune system (immunopotentiation) might protect the embryo from diabetes teratogenicity. Therefore, in the present study we further inquired whether diabetes teratogenicity might be associated with alterations in the level of immune effector cells in systemic and local lymphoid organs as well as in the uterus throughout pregnancy and whether the protection exerted by maternal immunopotentiation might be realized through its effect on those cells. Streptozotocin-induced diabetes in ICR mice was found to reduce pregnancy rate and fetal weight while increasing the resorption rate and the percentage of litters with malformed fetuses. These teratogenic effects were accompanied by a decreased percentage of cells expressing Mac-1, Thy-1.2, CD4 or CD8 in the spleen and inguinal as well as paraaortic lymph nodes, except for Mac-1 expression by splenocytes, which increased significantly in the beginning of pregnancy and decreased later. A different pattern was observed in the uterus, when the percentage of cells expressing these markers tended to increase in the beginning of pregnancy and decrease later. Intrauterine immunopotentiation with rat splenocytes was found to improve the reproductive performance of diabetic animals. This protective effect was accompanied by a general normalization of the level of the various cell surface markers, when in most cases their expression returned to that found in nonimmunopotentiated mice. Our results suggest that the protection exerted by maternal immunopotentiation on the embryo against diabetes teratogenicity might be mediated via its effect on the level of immune effector cells localized to uterus and lymphoid organs, which was found to be altered in diabetic mice.
Savion
S
S
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. shoshans@post.tau.ac.il
Gidon-Dabush
S
S
Fein
A
A
Torchinsky
A
A
Toder
V
V
D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology / Q000473:pathology; D005260:Female; D020567:Fetal Weight; D005333:Fetus / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications* / Q000276:immunology / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D014599:Uterus / Q000276:immunology / Q000473:pathology*