What Do We Know About Spontaneous Abortion Mechanisms?

Clark, David A.; Chaouat, Gérard

doi:10.1111/j.1600-0897.1989.tb00544.x

Cited by 62 publications

(22 citation statements)

References 80 publications

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“…IL-2 probably plays important roles in the CBAXDBA/2 system, since the injection of anti-IL-2 antibodies results in decreased resorption rates [2]. IL-2 and TNFao may synergize to stimulate lymphokine-activated killers (LAK) [43], which have been shown to lyse trophoblast cells [44,45].…”

Section: Discussionmentioning

confidence: 99%

“…covery of the CBAXDBA/2 mouse combination, matings between which result in abnormally high rates of spontaneous fetal resorptions [2,11,12]. Matings between CBA/J females and DBA/2 males result in resorption of up to 50% of the litter, while normal matings with males bearing the same H-2 haplotype as DBA/2 result in less than 7% resorptions.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Cytokines in Placentas of Mice Undergoing Immunologically Mediated Spontaneous Fetal Resorptions1

Tangri

Raghupathy

1993

Biology of Reproduction

120

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It is clear that the immune system and the reproductive system interact with and influence each other and that the immune system can have positive and negative regulatory effects on the outcome of pregnancy. The discovery of murine models of immunologically mediated spontaneous fetal resorptions has proved to be very useful for the study of immunological influences on pregnancy. In an attempt to elucidate the mechanisms underlying pregnancy impairment in one such "natural" model of pregnancy loss, we compared the expression of the cytokines tumor necrosis factor alpha, interferon tau, and interleukin-2 in placental tissue from a resorption-prone strain combination with the expression from a normal combination. We found significantly enhanced expression of these three cytokines in placentas from the resorption-prone combination using dot-blot hybridization and Northern hybridizations. Since these cytokines are abortifacients in vivo and have detrimental effects on the placenta, and hence on fetal development and survival, our demonstration of enhanced expression of these deleterious cytokines may give insight into the mechanisms involved in immunologically mediated spontaneous abortions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Cytokines in Placentas of Mice Undergoing Immunologically Mediated Spontaneous Fetal Resorptions1

Tangri

Raghupathy

1993

Biology of Reproduction

120

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“…This is achieved with the help of oth er factors reported to be associated with the tolerance to and maintenance of normal pregnancy, such as prosta glandins, interleukin-2 inhibitors, histamine, GM-CSF, CSF-1, etc. [2][3][4][5][43][44][45][46][47], Finally, the presence of cytotoxic antibodies to immu nizing cells was found to correlate with the appearance of the suppressors and reduced response to immunizing cells. This contrasting association between the two arms of the immune response in immunized women is proba bly balanced by active idiotypic and anti-idiotypic anti bodies that we and others have recently described [38,48], Our study shows that immunizing habitually aborting women with their husbands' cells alters the lymphocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

Differential Suppression Activity Induced by Paternal Leukocyte Immunization in Habitual Abortion

Behar¹,

Carp²,

Livneh

et al. 1993

Gynecol Obstet Invest

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In order to investigate the possible role of suppressor cells in paternal leukocyte immunization to prevent recurrent miscarriages, peripheral blood lymphocytes from habitually aborting women before and after immunization were assessed. Immunization-induced suppressor activity as shown by (1) rise in CD8-positive cells and a decline in the CD4/CD8 ratio, (2) failure of cyclosporine A to inhibit the proliferation of phytohemagglutinin- and alloantigen-stimulated cells and (3) unresponsiveness to the immunizing spouses’ antigen. These findings resembled those in normal pregnant women. Hence, paternal leukocyte immunization may induce specific and nonspecific T cell suppression which may induce the immune tolerance necessary to maintain pregnancy.

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“…Spontaneous abortions are common medical events and may account during the first trimester for one fifth of all intended pregnancies [1]. The mechanisms mediating the survival of the embryo/fetus and those leading to pregnancy loss (PL) are far from understood.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 10 Gene Promoter Polymorphisms in Women with Pregnancy Loss: Preferential Association with Embryonic Wastage1

Cochery-Nouvellon¹,

Nguyên²,

Attaoua³

et al. 2009

Biology of Reproduction

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Interleukin 10 (IL10) is associated with maternal immunotolerance. IL10 also down-regulates decidual cell tissue factor expression, the main molecule triggering coagulation activation: this antithrombotic effect may protect the umbilicoplacental vasculature from the 10th wk of gestation onward. IL10 down-regulation may thus dispose to early pregnancy loss (PL) due to maternal immunotolerance defect or late pregnancy failure due to placental vascular insufficiency. IL10 gene promoter polymorphisms associated with cytokine down-regulation may help to identify the actual and probable mechanisms of IL10 modulation in pregnancy outcomes. We investigated the following four IL10 promoter polymorphisms associated with IL10 down-regulation: two single-nucleotide polymorphisms rs1800871 and rs1800872 and two polymorphic CA repeat microsatellites IL10 X78437.2:g8134CA(14_29) and IL10 X78437.2:g.5325CA(11_15). Each microsatellite was analyzed as a biallelic polymorphism. Based on a review of the literature, we define a short allele and a long allele for each microsatellite. We compared their frequencies in early PL occurring before 10 wk of amenorrhea (n = 342) and in PL occurring later on (n = 123). The mutated alleles rs1800871T (odds ratio, 3.083; 95% confidence interval, 1.984-4.792) and rs1800872A (odds ratio, 3.013; 95% confidence interval, 1.924-4.719) were associated with early PL. The haplotype rs1800872A/rs1800871T/X78437.2:g.8134CA[14_25]/X78437.2:g.5325CA[11_13], which includes the two mutated alleles, was significantly associated with the risk of early PL in a dose-dependent manner. Positivity for one haplotype was significantly associated with a 5.6-fold increase in the risk of early pregnancy failure, and positivity for two haplotypes was associated with an 8-fold increase in risk. In women with PL, some polymorphisms of the IL10 gene promoter seem to be constitutional risk factors for early (embryonic) pregnancy failure.

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What Do We Know About Spontaneous Abortion Mechanisms?

Cited by 62 publications

References 80 publications

Expression of Cytokines in Placentas of Mice Undergoing Immunologically Mediated Spontaneous Fetal Resorptions1

Expression of Cytokines in Placentas of Mice Undergoing Immunologically Mediated Spontaneous Fetal Resorptions1

Differential Suppression Activity Induced by Paternal Leukocyte Immunization in Habitual Abortion

Interleukin 10 Gene Promoter Polymorphisms in Women with Pregnancy Loss: Preferential Association with Embryonic Wastage1

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