PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9806572

Microsatellite mutations in spontaneously aborted embryos.

D A Spandidos·E Koumantakis·S Sifakis·G Sourvinos
View original source ↗Export metadata ↓

Abstract

OBJECTIVE: To evaluate the incidence of microsatellite instability in spontaneously aborted embryos. DESIGN: Retrospective study. SETTING: Laboratory of Clinical Virology and Department of Obstetrics and Gynecology, University Hospital, Medical School, University of Crete. PATIENT(S): Thirty-five women in whom spontaneous abortions occurred between the 6th and 20th weeks of pregnancy. INTERVENTION(S): Thirty-five aborted embryonic tissues were analyzed with seven microsatellite markers, and their haplotypes were compared with the corresponding pattern of their parents. MAIN OUTCOME MEASURE(S): Microsatellite DNA. RESULT(S): Microsatellite instability was observed in 8 of 35 cases (23%). In 7 of 8 positive cases, microsatellite instability was restricted to one of the seven microsatellite markers, whereas in one case, three microsatellite markers were affected by instability. A statistically significant association was found between microsatellite instability and a previous normal childbirth. CONCLUSION(S): Genetic instability is a detectable phenomenon in spontaneous abortions, representing a significant increase in the mutational rate of the embryo and providing evidence for a mechanism associated with the phenomenon of spontaneous abortion. We conclude that this elevated mutational rate affects active genomic sequences that play a critical role in the viability of the embryo, leading to cell death and abortion.

Explore related subjects

Abortion, SpontaneousAdolescentAdultFemaleGenetic HeterogeneityHaplotypesHumansMicrosatellite RepeatsMutationPolymerase Chain ReactionPregnancyPregnancy Trimester, FirstPregnancy Trimester, SecondRetrospective StudiesJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D A Spandidos, E Koumantakis, S Sifakis, G Sourvinos. 1998. Microsatellite mutations in spontaneously aborted embryos.. https://doi.org/10.1016/s0015-0282(98)00279-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Cyclosporin a improves pregnancy outcome by promoting functions of trophoblasts and inducing maternal tolerance to the allogeneic fetus in abortion-prone matings in the mouse.

The embryo expresses paternal antigens foreign to the mother, and therefore has been viewed as a natural allograft. Cyclosporin A (CsA) is an immunosuppressant for preventing allograft rejection. Little is known, however, about the modulating effect of CsA on the materno-fetal relationship. In this study, pregnant CBA/J female mice mated with DBA/2 or BALB/c male mice as abortion-prone and normal pregnancy matings were administered, respectively, with CsA at Day 4 of gestation. We demonstrated that the administration of CsA at the window of implantation resulted in maternal T-cell tolerance to paternal antigen, and it improved pregnancy outcome in the CBA/J multiply sign in box DBA/2 abortion-prone matings. CsA administration enhanced Th2 and reduced Th1 cytokine production at the materno-fetal interface, and it expanded peripheral CD4(+)CD25(+) FOXP3(+) regulatory T cells in abortion-prone matings, implying development of Th2 bias and regulatory T cells. On the other hand, we observed that treatment with CsA led to enhanced growth and invasiveness of trophoblasts in the abortion-prone matings. Together, these findings indicate that CsA in lower dosages can induce materno-fetal tolerance and improve the biologic functions of trophoblast cells in the abortion-prone matings, leading to a successful pregnancy, which is useful in clinical therapeutics for spontaneous pregnancy wastage and other pregnancy complications.

Abortion, Spontaneous↗
PubMed2007

Interleukin 10 regulates inflammatory cytokine synthesis to protect against lipopolysaccharide-induced abortion and fetal growth restriction in mice.

Interleukin 10 (IL10) is a potent immune-regulating cytokine and inhibitor of inflammatory cytokine synthesis. To evaluate the anti-inflammatory role of IL10 in pregnancy, the response of genetically IL10-deficient mice to low-dose lipopolysaccharide (LPS)-induced abortion was examined. When IL10-null mutant C57Bl/6 (Il10(-/-)) and control (Il10(+/+)) mice were administered low-dose LPS on Day 9.5 of gestation, IL10 deficiency predisposed to fetal loss accompanied by growth restriction in remaining viable fetuses, with an approximately 10-fold reduction in the threshold dose for 100% abortion. After LPS administration, inflammatory cytokines tumor necrosis factor-alpha (TNFA) and IL6 were markedly increased in serum, uterine, and conceptus tissues in Il10(-/-) mice compared with Il10(+/+) mice, with elevated local synthesis of Tnfa and Il6 mRNAs in the gestational tissues. IL1A and IL12p40 were similarly elevated in serum and gestational tissues, whereas interferon gamma (IFNG) and soluble TNFRII content were unchanged in the absence of IL10. Recombinant IL10 rescued the increased susceptibility to LPS-induced fetal loss in Il10(-/-) mice but did not improve outcomes in Il10(+/+) mice. IL10 genotype also influenced the responsiveness of mice to a TNFA antagonist, etanercept. Fetal loss in Il10(-/-) mice was partly alleviated by moderate or high doses of etanercept, whereas Il10(+/+) mice were refractory to high-dose etanercept, consistent with attenuation by IL10 status of TNFA bioavailability after etanercept treatment. These data show that IL10 modulates resistance to inflammatory stimuli by downregulating expression of proinflammatory cytokines TNFA, IL6, IL1A, and IL12, acting to protect against inflammation-induced pathology in the implantation site.

Abortion, Spontaneous↗
PubMed2007

Glucose transporter isoform-3 mutations cause early pregnancy loss and fetal growth restriction.

Glucose transporter isoform-3 (GLUT3) is the trophoblastic facilitative glucose transporter. To investigate the role of this isoform in embryonic development, we created a novel GLUT3-null mouse and observed arrested early embryonic development and loss at neurulation stage when both alleles were mutated. This loss occurred despite the presence of other related isoforms, particularly GLUT1. In contrast, when a single allele was mutated, despite increased embryonic cell apoptosis, adaptive changes in the subcellular localization of GLUT3 and GLUT1 in the preimplantation embryo led to postimplantation survival. This survival was compromised by decreased GLUT3-mediated transplacental glucose transport, causing late-gestation fetal growth restriction. This yielded young male and female adults demonstrating catch-up growth, with normal basal glucose, insulin, insulin-like growth factor-I and IGF-binding protein-3 concentrations, fat and lean mass, and glucose and insulin tolerance. We conclude that GLUT3 mutations cause a gene dose-dependent early pregnancy loss or late-gestation fetal growth restriction despite the presence of embryonic and placental GLUT1 and a compensatory increase in system A amino acid placental transport. This critical life-sustaining functional role for GLUT3 in embryonic development provides the basis for investigating the existence of human GLUT3 mutations with similar consequences during early pregnancy.

Abortion, Spontaneous↗