Effect of zeranol on expression of apoptotic and cell cycle proteins in murine placentae.

ABSTRACT

Mycotoxins are chemicals produced by fungus and many of them are toxic to humans. Zeranol is a mycotoxin used to promote growth in cattle in North America; yet such a practice draws concern about the residual compound in meat in European countries. In the present study, the toxicity of zeranol was tested in a mouse model for reproduction. Pregnant ICR mice were given p.o. daily doses of zeranol at 0, 1, 10, 100mg/kg for 4 days (from E13.5 to E16.5). Increased rates of fetal resorption at late gestation (E17.5) and preterm birth (mice treated with zeranol. The apparent factors causing these perinatal conditions were subsequently investigated. Perturbation of cell death or proliferation-related proteins might deter the growth and maintenance of the placentae, and the subsequent fetal resorption and preterm birth. Placental tissue isolated from pregnant mice at E17.5 showed that the expressions of Cdk2 and 4, Cyclin D1 and Bcl-xL were reduced in zeranol-treatment groups. The downregulations might signify growth or maintenance failure in the placentae. Furthermore, reduction in the signaling proteins Erk-1/2 in the placentae could trigger the decrease in the cell cycle/apoptosis proteins. In addition, relaxin is associated with preterm labor. An increase in placental Relaxin-1 expression could also contribute to early delivery in this study. Result of the current study suggested that exposure to zeranol might introduce adverse effect in pregnancy.