Effect of a pure nonsteroidal antiestrogen, CDRI-85/287, on implantation— associated histological and biochemical changes in the rat uterus

The effect of compound CDRI-85/287, a pure, nonsteroidal antiestrogen, on implantation-associated changes in rat uterus were studied. Results provide a clear correlation between the antideciduogenic action of 85/287 (0.05 mg/kg in days 1–5 post-coitum or 2.5 mg/kg on day 1 post-coitum) and the time of its administration in relation to the secretion of prenidatory luteal phase estrogen. The antiestrogenic nature of the compound is further highlighted by inhibition of estradiol-induced increase in vascular permeability. In the present study, differences in the pattern of biochemical maturation of the pregnant, pseudopregnant and 85/287-treated rat uterus have also been illustrated. As compared to the pregnant rat uterus, absence of (the blastocyst and) decidualizing tissue in the pseudopregnant rat uterus accounts for the low uterine weight, protein, RNA, phospholipids and alkaline phosphatase at the time of implantation. Post-coital treatment with 85/287 (2.5 mg/kg, oral) inhibited increase in these parameters at the time of implantation. Glycogen levels which were lowered in the pregnant rat uterus on days 5 and 6, remain unaltered in the pseudopregnant and 85/287-treated rat uteri, suggesting nonutilization of this energy substrate. These findings provide sufficient evidence that the antiimplantation activity of 85/287 is due to its antiestrogenic property.