Developmental response of zygotes exposed to similar mutagens

Differential Susceptibility of Rat Embryos to Methyl Methanesulfonate During the Pregastrulation Period

“…Alternatively, embryos on gestation days 0 and 3 to 6 may be more sensitive to MMS than are those on days 1 and 2. A single intraperitoneal injection with MMS into female mice on day 0 of gestation, corresponding to the zygote stage of embryonic development, was previously shown to result in congenital anomalies (Generoso et al, 1991). The incidence increased approximately 7-and 12-fold at the dose of 75 and 100 mg/kg, respectively.…”

“…A significant increase in preimplantation loss was observed only in the GD0 group. Treatment of mouse embryos with MMS at preimplantation stages was previously shown to induce their death both in vitro (Fabro et al, 1984;Iannaccone et al, 1987) and in vivo (Generoso et al, 1991;Rutledge et al, 1992;Nagao et al, 1997;Rutledge, 1997). Treatment of male rats or mice with MMS induces a dominant lethal phenotype in embryos d erived fro m th e ex pos ed sp er m (Ehling and Neuhauser-Klaus, 1990;Ashby et al, 1996) and chromosomal damage in gametes results in such a phenotype of embryos (Brewen et al, 1975;Katoh and Tanaka, 1980).…”

“…It was subsequently found, however, that exposure of pregastrulation mouse embryos to various agents, including xradiation, mutagens, or retinoic acid, can result in developmental malformations (Nagao et al, 1986(Nagao et al, , 1991(Nagao et al, , 1997(Nagao et al, , 2000Generoso et al, 1987Generoso et al, , 1988Generoso et al, , 1991Rutledge et al, 1992;Nagao, 1994Nagao, , 1996Jacquet et al, 1995). Indeed, the zygote and two-cell embryo in mice represent a window of susceptibility to the experimental induction of congenital anomalies by certain mutagens (Rutledge et al, 1992;Rutledge, 1997).…”

“…Indeed, the zygote and two-cell embryo in mice represent a window of susceptibility to the experimental induction of congenital anomalies by certain mutagens (Rutledge et al, 1992;Rutledge, 1997). A single intraperitoneal injection of pregnant mice with methyl methanesulfonate (MMS), an alkylating agent, at the pregastrulation stage increases pre-and postimplantation embryonic mortality and induces intrauterine growth retardation as well as malformations in term fetuses (Generoso et al, 1991;Rutledge et al, 1992;Rutledge, 1997). Given that few studies have examined developmental toxicology except in mice, with treatment of dams at pregastrulation stages of embryonic development, we have now investigated the effects of MMS on developing embryos, including the placenta, after oral treatment of pregnant rats at various times during the pregastrulation period.…”

Embryonic mortality and intrauterine growth retardation (IUGR) associated with placental alterations in pregnant rats treated with methyl methanesulfonate (MMS) at the peri-implantation stage

“…It was subsequently found, however, that exposure of pregastrulation mouse embryos to various agents, including x-radiation, mutagens or retinoic acid, can result in developmental malformations as well as in embryonic mortality and intrauterine growth retardation (IUGR) (Spielmann and Eibs 1978;Nagao et al, 1986Nagao et al, , 1991Nagao et al, , 1997Nagao et al, , 2000Generoso et al, 1987Generoso et al, , 1988Generoso et al, , 1991Rutledge et al, 1992Rutledge et al, , 1994Nagao, 1994Nagao, , 1996Jacquet et al, 1995). The zygote and subsequent pregastrulation stages of mice are thus susceptible to chemical perturbations that result in abnormal development of the conceptus.…”