[An application of in vitro fertilization--embryo culture--embryo transfer system on the drug safety evaluation: fertility test of male mice administered with the anticancer drug].
We examined an application of in vitro fertilization--embryo culture--embryo transfer system for reproductive and developmental study on the drug safety evaluation in mice. The male mice at 10 weeks of age were administered intravenously with a single dose of 75 mg/kg of the anticancer platinum complex (DWA 2114R) which inhibits DNA synthesis. Four to six weeks after administration, the males were mated with the superovulated females. Fertilization rates were significantly lower than the controls at each weeks after the administration. Furthermore, delayed formation of pronucleus was observed as compared with the control. Four weeks after administration, the preimplantation development to blastocyst stage of those embryos in vitro and the survival rates on the day 17 of gestation after embryo transfer suggested that a DNA synthesis in germ cells during maturation was inhibited and/or prevented by DWA 2114R. The results of in vitro fertilization reflected its sperm concentration rather than the administration of DWA 2114R. Thus, an analysis of the delayed formation of pronucleus observed fertilization in vivo could not done in detail. To use for the drug safety evaluation, there exist plenty of room for improvement in this system. These results have showed that the embryo culture and the embryo transfer are useful techniques as the reproductive and developmental study on the drug safety evaluation. These techniques bring additional informations on the pre- and post-implantation development in vivo.
Ueda
O
O
CSK Research Park, INC., Tokyo, Japan.
Suzuki
H
H
Matsuoka
A
A
Sugiyama
O
O
Adachi
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016190:Carboplatin / Q000009:adverse effects / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004624:Embryo Transfer; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005307:Fertilization in Vitro; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D000970:Antineoplastic Agents; C058816:DWA 2114; D004247:DNA; D016190:Carboplatin