In vitroZidovudine-Induced Apoptosis Demonstrated by a Model of Placental Histoculture Useful for the Study of the Apoptotic Effects of Antiretroviral Drugs

This study aims to evaluate the use of a placenta histoculture system based on placental villi culture on collagen sponge gels at the liquid/air interface, for the detection of zidovudine-induced apoptosis. Explant cultures from full term placentas were exposed to different concentrations of zidovudine (1, 10, 100 uM) up to 7 days and samples were analysed for apoptosis with different methods after 3, 24, 48 hours and 7 days of exposure. Apoptotic phenomena were demonstrated at 10 and 100 uM zidovudine, more delayed at the lowest concentration: this demonstrates that zidovudine-induced placenta apoptosis in vitrois both time- and dose-dependent and that also concentrations near to those achievable in vivomight cause placenta apoptosis. This has to be taken into account when considering possible consequences of antiretroviral treatments during pregnancy. Placental histocultures on collagen sponge cells are a reliable tool for the study of antiretroviral-induced toxicity in placenta: in fact, explants cultured for more prolonged periods (up to 7–14 days) in a “physiological milieu” allow the detection of biological effects otherwise not evident in the commonly used, short-term, placental cultures.