DEFICIENT SYNCYTIOTROPHOBLAST TUMOR-NECROSIS-FACTOR-ALPHA CHARACTERIZES FAILING FIRST-TRIMESTER PREGNANCIES IN A SUBGROUP OF RECURRENT MISCARRIAGE PATIENTS

Pregnancy failure in mice has been associated with increased placental concentrations of the pro-inflammatory cytokine tumour necrosis facto r-alpha (TNF-alpha). To investigate the role of uterine TNF-alpha in h uman 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) an d (iii) with a history of recurrent pregnancy loss [>3 consecutive pre gnancy losses (n = 26)] undergoing a further miscarriage. Formalin fix ed tissues were examined for TNF-alpha mRNA (in-situ hybridization) an d protein (immunohistochemistry). In decidua from all three groups, TN F-alpha in and mRNA were co-localized to the decidual stroma, the lumi nal 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 syncyt iotrophoblast 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 preg nancy (P < 0.001). TNF-alpha mRNA was also localized exclusively to th is layer. This may be a secondary effect caused by a different mechani sm of pregnancy loss unique to this subgroup.