Midgestational abnormalities associated with in vitro preimplantation N-methyl-N-nitrosourea exposure with subsequent transfer to surrogate mothers.

Mouse blastocyst functions have been shown to be disrupted by in vitro exposure to N-methyl-N-nitrosourea (MeNU). After exposure, the chemically treated blastocysts were transferred to the uteri of pseudopregnant surrogate mothers. Implantation rate and birth rate have been shown previously to decrease in a concentration-dependent manner. Because of the large progressive decrease in the 50% effective concentration (EC50) for cytotoxicity, implantation rate, and live birth rate, we have investigated the midgestational effects of preimplantation exposure to MeNU after the transfer of treated embryos to surrogate mothers. A concentration-dependent decrease in normal implantation and a concurrent concentration-dependent increase in resorption number was observed in surrogates sacrificed at gestational age day 12 or day 15. Gross malformations were significantly increased by preimplantation exposure, in vitro, to MeNU. Fetal body length did not differ between fetuses developed from solvent-treated blastocysts and those that developed from natural pregnancies (nontransferred control) at either gestational age examined. Fetal body length was significantly shorter in fetuses developed from MeNU-treated blastocysts.