Mouse Model for the Treatment of Immune Pregnancy Loss

Abstract

Spontaneous abortions can be associated with preimplantation embryo loss, implantation problems and a variety of postimplantation pregnancy failures. The long list of possible causes for the postimplantation pregnancy loss includes, among others, genetic abnormalities in fetus, anatomical abnormalities of the uterus, endocrinological insufficiency, and microbiological problems. However, more than 50% of recurrent miscarriages still have no recognized causes. The concept that many such abortions may be immunologically mediated has gained increasing support over the years. Moreover, immunization of such women with husband's or third party leukocytes has resulted in more than 70% of subsequent pregnancies resulting in live births. Since neither the mechanisms leading to pregnancy loss nor the success of immunotherapy are clear, the set-up of animal models for recurrent abortions would be of supreme significance. Our recent data show that immunopotentiation of maternal immune system by Complete Freund Adjuvant significantly improves pregnancy rate in CBA x DBA/2 mouse combination with high percentage of fetal resorptions. This effect is followed by decrease of IL 2 production in spleen; increase of MAC 1-positive cells at placenta; amplification of suppressive activity of local and systemic lymphocytes and by reverse of embryotoxic effect of maternal serum. Data obtained in this model seems to be valuable in substantiation of rationale for nonspecific immunotherapy of human abortions.

In Vitro secretion of tumor necrosis factor-α and interleukin-1 by placental macrophages in various outcomes of pregnancy

“…Our findings agree with the data on increased contents of some cytokines in the amniotic fluid after premature labor [8,11,13]. Therefore, we assume that the rise in interleukin-1 and TNF-~ levels was due to the increase in secretory activities of placental macrophages.…”

“…Placental macrophages attract much attention as the most probable natural producers of cytokines involved in the reproduction, such as tumor necrosis fac- tor-a (TNF-a), interleukin-1, colony-stimulating factors, transforming growth factor-13, and interferons a and 7 [3][4][5]13,14]. Exogenous (infections) and endogenous (cytokines, hormones, etc.)…”

Morphology and function of placental macrophagesin vitro in different outcomes of pregnancy

“…In this connection activation of PM can be considered as an event associated with preterm or fullterm delivery [7,10,14]. Recent studies revealed a positive correlation between high levels of some cytokines (tumor necrosis factor-a, interleukin-1, and interleukin-6) produced by activated macrophages and the onset of preterm or full-term labor [9,12,14,16]. We investigated the relationship between labor activity at different terms of pregnancy and the degree of PM activation in vitro, which was evaluated by the level of MHC II antigen expression and phagocytic activity of cells mediated by Fc and C3 receptors.…”

ORIGINAL ARTICLE: Syngeneic Immune‐Dependent Abortions in Mice Suggest Paternal Alloantigen‐Independent Mechanisms

“…Interestingly, replacement of the DBA/2J sires with BALB/cJ (also haplotype d/d) sires results in only baseline abortion rates (matching syngeneic matings),14,16 indicating the haplotype mismatch, alone, is not sufficient to trigger the rejection response. Moreover, although abortion frequencies can be reduced by immunizing the CBA/J dams,14,36 this effect can be achieved using non-specific (antigen-independent) immunizations 37,38. Thus, although paternal alloantigens exist in the CBA/J × DBA/2J F1 fetuses, it is not yet clear what, if any, role these might play in the selective abortion process.…”