ABSTRACT: Experiments were performed to (1) verify the inhibitory effect of bovine trophoblast protein-1 (bTP-1) on uterine prostaglandin synthesis, (2) evaluate whether other interferon-α (IFN-α) molecules also inhibit prostaglandin secretion, and (3) test whether the enzyme 2′,5′-oligoadenylate synthetase (2-5A synthetase) can be induced in endometrium by interferon-α. In experiment 1, all interferon molecules (bTP-1, oTP-1, bIFN-α and hIFN-α) equally inhibited secretion of PGF and PGE2 from endometrial explant cultures obtained at day 17 of the estrous cycle. In experiment 2, endometrial explants obtained from day 17 of the cycle were cultured with and without bovine serum albumin (BSA; 50 μg/ml) and bIFN-α (0, 0.84, 4.2, and 42 nM). Addition of BSA to the culture medium greatly enhanced the accumulation of PGF into the medium. The bIFN-α inhibited accumulation of PGF and PGE2 in both the presence or absence of BSA by 12 h. All three concentrations of bIFN-α were equally effective in inhibiting prostaglandin accumulation. Additionally, all concentrations of bIFN-α increased the amounts of 2-5A synthetase in endometrium. In conclusion, these results confirm the inhibitory effect of bTP-1 on PGF release from endometrium and demonstrate that bTP-1 can also inhibit PGE2 secretion. Furthermore, other interferon-α molecules, including bIFN-α, hIFN-α, and oTP-1, also reduced PGF and PGE2 secretion in culture. It is likely, therefore, that conceptus and other interferon-α molecules exert similar effects on endometrium in vitro and that the antiluteolytic effects of bIFN-α in vivo are mediated in part by changes in endometrial prostaglandin synthesis.