Inhibition of post-implantation development of mouse blastocysts in vitro after cyclophosphamide treatment in vivo.

Abstract

IT has been widely believed that embryos, after treatment in the preimplantation period, either die before implantation or survive to term without being malformed1,2. But evaluation of the embryolethal effect of cyclophosphamide (CPA) before implantation in the rat has revealed effects of the early treatment on both embryo and mother around and after implantation3. Further investigations of the development of CPA-treated preimplantation rat embryos are impossible because rat embryos have not been cultured successfully in vitro beyond the time of implantation. On the other hand, routine culture of mouse embryos in vitro during the same period has been standardised4‐6. Such systems are sufficiently sensitive for investigations of genetically-determined abnormalities7,8 and the effects of in vitro exposure to ultraviolet and X irradiation9,10, 3H-thymidine11 and metabolic inhibitors12‐14. To elucidate further the action of CPA on the embryos after maternal treatment during the pre-implantation period, we have used mouse blastocysts to repeat our studies with CPA in the rat, and we have also cultured mouse blastocysts for 120 h from CPA-treated mothers. With concentrations of CPA that did not affect the morphology of blastocysts from treated mothers but only the cell number at the time of implantation, development of the blastocysts in vitro was inhibited in a dose-dependent manner. This system holds promise as a test for putative teratogens.