OBJECTIVES: The association between maternal celiac disease (CD) and both reduced fertility and increased risk
of adverse pregnancy-related events has been long documented. However, no evidences are available
regarding the pathogenic mechanisms of this link. The aim of this study was to determine whether
anti-tissue transglutaminase (anti-tTG) antibodies are involved in the damage of trophoblastic
cells in vitro .
METHODS: Human primary trophoblastic cells, isolated from term placenta, were exposed to anti-tTG immunoglobulin
G (IgG) antibodies, both commercially available and separated from sera of three
untreated celiac women. The ability of anti-tTG antibodies to bind to trophoblastic cells, invasiveness
of placental cells through a layer of extracellular matrix, and the activity of cellular matrix metalloprotease
(MMP) and cellular apoptosis were evaluated, as indicators of trophoblast damage, by
TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) and annexin V expression.
RESULTS: Anti-tTG IgG showed a specifi c dose- and time-dependent binding to human trophoblast. In addition,
trophoblastic cells, after being exposed to anti-tTG IgG antibodies, both commercially available and
separated from sera of celiac women, showed an impaired invasiveness, a decreased activity of
cellular MMP, and a greater percentage of TUNEL positivity and annexin V positivity.
CONCLUSIONS: We showed that the binding of anti-tTG antibodies to trophoblast might represent a key mechanism
by which the embryo implantation and pregnancy outcome are impaired in untreated celiac pregnant
women. Because healthy trophoblast development is essential for placental and fetal development,
these data provide a novel mechanism for CD-induced infertility, early pregnancy loss, and intrauterine
- Antibodies, Anti-Idiotypic
- Celiac Disease
- Cells, Cultured
- Flow Cytometry