Effect of paternal administration of an antiestrogen, tamoxifen on embryo development in rats.

We have earlier reported that oral administration of tamoxifen causes a dose-dependent reduction in the fertility of adult male rats. The decrease in fertility was mainly due to an increase in pre-implantation loss without an effect on fertilizing ability. During the study, an increased incidence of post-implantation loss of conceptuses sired by tamoxifen-treated male rats was observed. A detailed study was undertaken to investigate dose-related changes in pre- and post-implantation loss and the stage(s) of development at which these losses occurred. The present study demonstrates that tamoxifen treatment produced few normal litters as well as significantly increased pre-implantation loss without affecting the rate of fertilization. Also a significant increase in the number of degenerating embryos at the 2-4-cell stage (days 1-2 of gestation), retrieved from the oviduct/uterus of females mated with tamoxifen-treated males was observed. Histology of the resorbed fetuses, in both control and treated groups, showed presence of trophoblast outgrowth indicative of early placenta formation, which normally occurs on days 8-9 of gestation. The present results suggest that pre-implantation loss occurred at the 2-4-cell stage and the post-implantation loss occurred around days 8-9 of gestation, i.e. around midgestation. The possible effects of paternal tamoxifen treatment on embryogenesis may be due to the reduction of androgens or by the blockage of the estrogen receptor by tamoxifen, thereby affecting germ cell maturation during spermatogenesis.