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Human Reproduction, Vol 12, 1313-1320, Copyright © 1997 by Oxford University Press


ARTICLES

Deficient syncytiotrophoblast tumour necrosis factor-alpha characterizes failing first trimester pregnancies in a subgroup of recurrent miscarriage patients

RG Lea, M Tulppala and HO Critchley
Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, UK.

Pregnancy failure in mice has been associated with increased placental concentrations of the pro-inflammatory cytokine tumour necrosis factor- alpha (TNF-alpha). To investigate the role of uterine TNF-alpha in human first trimester miscarriage, we have collected human decidual and trophoblast tissue from women (i) undergoing surgical termination of pregnancy (n = 27), (ii) undergoing a sporadic miscarriage (n = 20) and (iii) with a history of recurrent pregnancy loss [>3 consecutive pregnancy losses (n = 26)] undergoing a further miscarriage. Formalin fixed tissues were examined for TNF-alpha mRNA (in-situ hybridization) and protein (immunohistochemistry). In decidua from all three groups, TNF-alpha protein and mRNA were co-localized to the decidual stroma, the luminal surface of some maternal vessels and to the glandular epithelium. Chorionic villi from the normal pregnancy and the sporadic miscarriage group exhibited co-localized TNF-alpha protein and mRNA in the syncytiotrophoblast and cytotrophoblast. In the recurrent miscarriage group, however, 63.6% of the biopsies showed positive immunostaining in only the cytotrophoblast, compared with 4.0% of women undergoing surgical termination of pregnancy and 0.0% of women with a sporadic failed pregnancy (P < 0.001). TNF-alpha mRNA was also localized exclusively to this layer. This may be a secondary effect caused by a different mechanism of pregnancy loss unique to this subgroup.
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