Effects of DL111-IT or combined with RU486 on uterine polyamines biosynthesis in rats during early gestation

DL111-IT, a non-hormonal contragestional agent, revealed synergistic effects in combination with mifepristone (RU486) in some species. The present study was undertaken to clarify the rule of DL111-IT when used alone or plus RU486 on uterine polyamines biosynthesis, histologic alteration of decidual cells, and antifertility activity in rats. The levels of polyamines in pregnant rat uterus were determined by formed benzoyl chloride derivatives of polyamines for RP-HPLC. The results showed that all the treated groups including DL111-IT 2.8 mg (.) kg(-1) d(-1), RU486 3.0 mg (.) kg(-1) d(-1), and DL111-IT 0.56 mg (.) kg(-1) d(-1) plus RU486 0.6 mg (.) kg(-1) d(-1) caused 100% early pregnancy arrest. Uterine putrescine, spermidine, and spermine levels in comparison with vehicle control were declined significantly from d7 of gestation (1 day after treatment) to d9 or d14 (3 days or 8 days after treatment) by Duncan's multiple range test, and accompanied by histologic alterations, edema, degeneration and dissolution of decidual cells with nuclei indefinite in appearance on d8 of gestation (2 days after treatment). The combined administration at lower doses caused the most injury. The data verified that the decrease in uterine polyamine levels and subsequent decidual cells injuries were the critical role of early pregnancy arrest induced by DL111-IT or RU486. The two compounds used in combination with lower dosages revealed greatly synergistic effects. (C) 2001 Elsevier Science Inc. All rights reserved.