TNF-ALPHA MESSENGER-RNA AND PROTEIN EXPRESSION IN THE UTEROPLACENTAL UNIT OF MICE WITH PREGNANCY LOSS

An elevated expression of TNF-alpha in embryonic microenvironment was found to be associated with postimplantation loss, In this work, we ex amined the pattern of TNF-alpha expression at both the mRNA and the pr otein level as well as the distribution of TNF-alpha receptor mRNA in the uteroplacental unit of mice with induced (cyclophosphamide-treated ) or spontaneous (CBA/J x DBA/2J mouse combination) pregnancy loss. RN ase protection analysis demonstrated an increase in TNF-alpha mRNA exp ression in the placentae of mice with pregnancy loss compared with tha t in control mice. TNF-alpha messages were localized to the uterine ep ithelium and stroma as well as the giant and spongiotrophoblast cells of the placenta. The intensity of the hybridization signal in placenta e of mice with pregnancy loss was substantially higher than that in co ntrol mice. The up-regulation of TNF-alpha mRNA was accompanied by an increase in the expression of TNF-alpha receptor I mRNA in the same ce ll populations. The elevation of TNF-alpha production was also demonst rated at the protein level. Western blot analysis showed an increased level of the 18- and 26-kDa TNF-alpha protein species in the uteroplac ental unit of mice with pregnancy loss. Immunostaining revealed TNF-al pha-positive leukocytes located in the uterus and placenta. Finally, m e found that immunization of mice with cyclophosphamide-induced pregna ncy loss while decreasing the resorption rate in these females resulte d in a decline in TNF-alpha expression at the fetomaternal interface, These data clearly suggest an involvement of TNF-alpha in pathways lea ding to both spontaneous and induced placental death.