Attenuating effect of zinc on abnormal placental morphology in 6-mercaptopurine treated rats.

Pregnant Sprague-Dawley rats were fed diets containing 9 (marginal level), 100 (control level), or 1,000 (very high level) ppm zinc and were given a single intraperitoneal injection of 6-mercaptopurine (6-MP, 55 mg/kg) or an equivalent volume of carboxymethylcellulose on day 11 of gestation. Live young and their placentas were recovered at surgery on day 21 of gestation: they were weighed, measured, and placentas were examined histologically. Placentas from drug treated animals were smaller in diameter and lighter in weight than controls; however, the placentas of animals fed the 1,000 ppm zinc diet were significantly heavier than those of the other drug-treated groups. Histologically, the placentas of the 6-MP treated dams showed a highly disproportionate reduction in the labyrinthine layer with larger, less subdivided maternal sinuses than in controls, reduction of fetal vasculature, vesiculation of trophoblast nuclei, deposition of PAS positive material in the septal wall, and fibrinous degeneration of trophoblast cells. These morphological changes were reduced in placental tissues of drug treated rats given 1,000 ppm of zinc. In contrast, no placental abnormalities were observed in rats not treated with 6-MP.