Maternal Alloimmune Stimulation: Variable actions

Carp, Howard; Torchinsky, Arkady; Toder, V.

doi:10.1007/978-94-011-4197-0_20

Cited by 3 publications

(5 citation statements)

References 60 publications

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“…It was earlier demonstrated that maternal immunopotentiation may increase the embryo's resistance to the effect of the embryolethal and teratogenic stimuli, whether chemical, physical, or intrinsic [21,[30][31][32]. In this work, we have found that maternal immunopotentiation increased the level of TGF-β2 mRNA and protein expression in the uteri and placentae of diabetic mice at all examined time points.…”

Section: Discussionsupporting

confidence: 63%

Diabetes teratogenicity in mice is accompanied with distorted expression of TGF‐β2 in the uterus

Fein

Magid

Savion

et al. 2001

Teratog Carcinog Mutagen

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Early embryonic deaths as well as malformed newborns are among complications of the diabetic pregnancy. Cytokines and growth factors operating in the embryonic vicinity are found to be among factors that determine the sensitivity of embryos to external and internal detrimental stimuli, including diabetes. Transforming Growth Factor-β2 (TGF-β2) has been shown to be essential for embryonic development and survival. In the present work, we evaluated the pattern of TGF-β2 expression in the uterus of streptozotocin-induced diabetic mice, demonstrating a decreased reproductive performance and elevated percentage of litters with severely malformed fetuses. Since stimulation of the maternal immune system was found to increase the resistance of mouse embryos to the teratogenic effect of diabetes, the effect of immunopotentiation on the expression of the cytokine was also investigated. TGF-β2 expression was studied at the mRNA level by using the in situ hybridization technique and at the protein level by using the immunohistochemical analysis. A clear decrease in TGF-β2 mRNA expression in the uterus of diabetic mice was observed at examined time points: days 1, 5, and 9 of pregnancy. Also, an evident reduction in TGF-β2, the protein expression in the uterus of diabetic mice, was demonstrated at these time points. Maternal immunopotentiation that improved the reproductive performance of diabetic mice and reduced the number of the litters with malformed fetuses was also accompanied by a clear increase in the level of TGF-β2 mRNA expression in the pregnant uteri. The above results clearly demonstrate that the embryotoxic effect of diabetes is accompanied by an alteration of TGF-β2 ex- pression. Immunopotentiation that was shown to improve the reproductive performance of the diabetic mice was accompanied by a partial normalization of TGF-β2 expression in embryonic vicinity. Teratogenesis Carcinog. Mutagen. 22:59-71, 2002.

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Section: Discussionsupporting

confidence: 63%

Diabetes teratogenicity in mice is accompanied with distorted expression of TGF‐β2 in the uterus

Fein

Magid

Savion

et al. 2001

Teratog Carcinog Mutagen

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“…The balance between these two families of cytokines has been reported to be altered in mice with a high incidence of spontaneous pregnancy loss 78 , 79 . Maternal immunopotentiation has been reported to improve the reproductive performance of these animals 79 , 82 . Maternal immunopotentiation has also been shown to increase the resistance of the embryos to developmental toxicants 83 …”

Section: Introductionmentioning

confidence: 99%

The Role of Pro‐ and Anti‐apoptotic Molecular Interactions in Embryonic Maldevelopment

Toder

Carp

Fein

et al. 2002

American J Rep Immunol

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“…For many years the placenta was thought to be nonimmunogenic as it does not express class II MHC molecules, and class I MHC expression is restricted to certain trophoblast cells. Neither class I nor II MHC molecules are expressed on the surface of human trophoblast in intimate contact with maternal blood (19), except nonclassical MHC class I molecules HLA-G, HLA-C and HLA-E (20). Expression of HLA-G may be beneficial for pregnancy.…”

Section: Basic Mechanisms Of Recurrent Spontaneous Abortion Mediated mentioning

confidence: 99%

“…The proposed experimental treatment of those patients could be immunization with paternal lymphocytes, though the exact mechanism through which this therapy exerts its effect is still unknown. Many authors suggest that lymphocyte alloimmunization alters the number and activity of particular subpopulations of peripheral blood and decidual lymphocytes and/or modulate of immunity in women with unexplained RSA by contra-shift in the balance of cytokine profiles away from Th 1 to a Th 2 profile after immunotherapy (19,22). In research of Hayakawa et al (30) seven of nine patients who exhibited remarkable decreases in Th 1 /Th 2 activity ratios became pregnant within 6 months after three courses of immunotherapy, and four women delivered healthy babies, while none of the three patients who exhibited an increased or unchanged Th 1 /Th 2 activity ratio had fullterm pregnancies (30).…”

Section: Basic Mechanisms Of Recurrent Spontaneous Abortion Mediated mentioning

confidence: 99%

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Induction of thymic tolerance as possibility in prevention of recurrent spontaneous abortion

Bubanovic¹

2003

Medical Hypotheses

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Summary A major process through which the immune system becomes tolerant to self-proteins involves the deletion of self-reactive cells in the thymus and/or inhibition of specific Th 1 cells clones. Deletion process includes two selection mechanisms in which the thymus eliminates unwanted thymocytes are known as positive selection and negative selection. The thymus is an antigenically privileged site, mainly for it is discrete by blood-thymus barrier. Many researches were shown that intrathymic inoculation of any antigen resulted in specific tolerance induction. The embryo/fetus and placenta are an allograft to which the mother must remain immunologically tolerant in order for the fetus to survive. Today, there is much interest focused on the immunology of recurrent spontaneous abortion (RSA). Up to 50% of RSA may be mediated by the immune system via inadequate maternal anti-paternal response. Nature of this maternal-fetal disturbance represents disbalance in Th 1 =Th 2 activity. Contra-shift in Th 1 =Th 2 activity is the basis for immunotherapy with paternal leukocyte immunization (PLI). PLI induce some kind of peripheral tolerance on embryonic/fetal/trophoblast antigens, but problems of central tolerance are still open. Intrathymic inoculation of fetal or paternal cells (like leukocyte, thymic dendritic cells, trophoblast cells) or paternal set of MHC molecules may cause central specific tolerance and may be a new possibility for immunotherapy in RSA patients. ª

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Maternal Alloimmune Stimulation: Variable actions

Cited by 3 publications

References 60 publications

Diabetes teratogenicity in mice is accompanied with distorted expression of TGF‐β2 in the uterus

Diabetes teratogenicity in mice is accompanied with distorted expression of TGF‐β2 in the uterus

The Role of Pro‐ and Anti‐apoptotic Molecular Interactions in Embryonic Maldevelopment

Induction of thymic tolerance as possibility in prevention of recurrent spontaneous abortion

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