Effects of Mitomycin C Treatment before Implantation on Development of Mouse Embryo

Abstract

ICR mice were treated intraperitoneally with mitomycin C (MMC) at a single dose of l‐5mg/kg on day 0, 1, 2 or 3 of pregnancy (vaginal plug = day G). Embryotoxicity and teratogenicity were examined at term. A dose‐dependent increase in fetal mortality and decrease in the number of implants, fetal weight or number of ossified sacral and caudal vertebrae were observed. The incidence of external malformation, umbilical hernia, significantly increased among the fetuses of dams treated with MMC at 5mg/kg on day 1, 2 or 3. Skeletal malformation failed to show significant increase though some fetuses from MMC‐treated mice were attended with multiple defects such as fusion of ribs or axial skeleton. Maternal contribution to and the direct action of MMC on embryonic development were investigated by embryo transfer. In regard to malformation inducement and decrease in implants, the maternal environment was found to have more significant effect than the direct action of this drug but both these factors are significantly responsible for increased fetal mortality and growth retardation.

Protection of the Gametes Embryo/Fetus From Prenatal Radiation Exposure

“…and Streffer 1988and Streffer , 1989Rutledge and Generoso 1989;Rutledge et al 1992Rutledge et al , 1994Muller et al 1994;Streffer 1995;Nagao 1996;Rutledge 2000). Nagao et al (1986) performed an interesting group of experiments demonstrating, at least in those studies, that when mitomycin C was administered on the second or third day postconception, many embryos died early and late and some were obviously malformed. When treated embryos were transferred to untreated dams or normal embryos were transferred to treated dams, Nagao et al (1986) observed that the malformations were due to the effect of mitomycin C on the mother, indicating that the malformations were due to a maternal toxic effect, not a direct effect on the zygote.…”

“…Nagao et al (1986) performed an interesting group of experiments demonstrating, at least in those studies, that when mitomycin C was administered on the second or third day postconception, many embryos died early and late and some were obviously malformed. When treated embryos were transferred to untreated dams or normal embryos were transferred to treated dams, Nagao et al (1986) observed that the malformations were due to the effect of mitomycin C on the mother, indicating that the malformations were due to a maternal toxic effect, not a direct effect on the zygote. Rutledge (2000) wrote a commentary on Nagao et al (1986) and concluded that the Nagao et al (1986) observations indicated that the malformations were due to a maternal toxic effect.…”

“…High exposure to ethylnitrosourea, retinoic acid, ethylene oxide, and high-dose radiation early in pregnancy have resulted in lethality and a small increased incidence of malformations (Russell 1950(Russell , 1956Streffer et al 1980;Nagao et al 1986;Generoso et al 1987Generoso et al , 1991Streffer and Molls 1987; The original quantity and unit used in the studies referenced was exposure expressed as roentgen. The dose given here is approximate whole-body absorbed dose in the mouse or rat in gray.…”

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.…”

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

“…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).…”