title: Possible role for TNF-alpha in early embryopathy associated with maternal diabetes in the rat.
abstract: Tumor necrosis factor (TNF) bioactivity was assessed in culture media conditioned with uterine cells collected from control or diabetic rats on days 5 and 8 of pregnancy. On both days, diabetic uterine cells released significantly more biologically active TNF than did control cells, and this activity was significantly decreased by the addition of anti-TNF-alpha antibodies but not by the addition of normal IgG when WEHI 164 cells were used as a target. When uterine tissues from day 5 or day 8 pregnant diabetic rats were tested by Northern blot analysis, TNF-alpha mRNAs were twofold more abundant than in control samples, but the difference was not statistically significant (P = 0.086 and 0.100, respectively). Immunohistochemical analysis of diabetic day 5 uterine sections revealed that most of the TNF-alpha synthesis occurs in the epithelium lining the uterine lumen. Finally, the growth of day-5 embryos in culture medium conditioned with day-5 diabetic uterine cells was significantly reduced when compared with that of embryos in medium conditioned with control cells. Embryonic development was markedly improved when anti-TNF-alpha antibodies were added to the diabetic-cell conditioned medium. Our data support the hypothesis that TNF-alpha may be implicated in the developmental deficiencies observed in preimplantation embryos from pregnant diabetic rats.
authors.affiliation: Physiology of Human Reproduction Research Unit, University of Louvain Medical School, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Pampfer
authors.forename: I
authors.initials: I
authors.lastname: Vanderheyden
authors.forename: Y D
authors.initials: YD
authors.lastname: Wuu
authors.forename: L
authors.initials: L
authors.lastname: Baufays
authors.forename: O
authors.initials: O
authors.lastname: Maillet
authors.forename: R
authors.initials: R
authors.lastname: De Hertogh
mesh_terms: D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology*; D017077:Culture Media, Conditioned; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D047108:Embryonic Development; D005260:Female; D007150:Immunohistochemistry; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation; D014599:Uterus / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha