The impairment of metrial gland development in tamoxifen exposed rats.

We examined the sequential histopathological changes in the placenta from rats exposed to tamoxifen. Tamoxifen was administered intraperitoneally at doses of 0 and 2 mg/kg/day on gestation days (GDs) 8, 9 and 10, and the placentas were sampled on GDs 11, 13, 15, 17, and 21. The fetal mortality rates in the tamoxifen group were increased up to 56%. However, there were no effects on the weights of live embryos/fetuses and their placentas. Histopathologically, the size of metrial gland in the tamoxifen group was reduced on all sampling times. The spiral arteries appeared less well developed in the hypoplastic metrial gland. A decrease in uterine natural killer (uNK) cells and mitotic uNK cells around the spiral arteries in the metrial gland was detected from GD 13 onward and on GDs 11 and 13, respectively. There were no obvious changes in the labyrinth zone or basal zone. We consider that the anti-estrogen effect of tamoxifen inhibits the proliferation of decidualized endometrial stromal cells in the metrial gland and leads to inhibition of the proliferative activity of uNK cells, followed by defective development of spiral arteries, and metrial gland hypoplasia. It is assumed that the metrial gland hypoplasia might be involved in the tamoxifen-induced embryo/fetus-toxicity.