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Cytogenetic studies on preimplantation mouse embryos exposed to methylnitrosourea in vivo
R Vogel1, I Granata, H Spielmann
1Max von Pettenkofer Institut, Federal Health Office (BGA), Berlin, West Germany.
Abstract:
Since exposure of mice to methylnitrosourea (MNU) during the preimplantation period can induce malformations and an increased postnatal death rate, direct embryotoxic effects were studied in preimplantation embryos shortly after treatment of pregnant mice on days 2 and 3 of gestation with single i.p. injections of 2.5, 5.0, and 10.0 mg/kg MNU. Embryos exposed to MNU for 24 h after treatment on day 2 showed a significant reduction of cell number and induction of sister chromatid exchange (SCE) frequency, but no structural chromosomal aberrations or inhibition of development during culture. Embryos exposed to MNU in vivo for 3 h on day 3 showed significantly reduced cell numbers, a significant inhibition of development in culture, and an increase in structural chromosome aberrations. Due to the high cytotoxicity of MNU, determination of SCE was not possible. The results indicate that MNU reaches preimplantation mouse embryos shortly after maternal treatment and that malformations seen at term and postnatal effects are probably induced by the direct action of MNU on early embryos. Furthermore, the importance of the time interval chosen for evaluation of toxicologic endpoints in preimplantation embryos is demonstrated.
Insights
Methylnitrosourea (MNU) exposure during early mouse development causes direct embryotoxic effects. This study shows MNU reaches preimplantation embryos, leading to developmental issues and potential malformations.
Area of Science:
- Developmental toxicology
- Reproductive toxicology
- Genetics and epigenetics
Background:
- Methylnitrosourea (MNU) is a known teratogen.
- Preimplantation embryos are susceptible to environmental insults.
- MNU exposure during gestation can lead to adverse outcomes.
Purpose of the Study:
- To investigate the direct embryotoxic effects of MNU on preimplantation mouse embryos.
- To determine the impact of MNU exposure timing on embryonic development and chromosomal integrity.
- To correlate early embryonic effects with observed malformations and postnatal mortality.
Main Methods:
- Pregnant mice were administered single i.p. injections of MNU (2.5, 5.0, 10.0 mg/kg) on gestation days 2 or 3.
- Preimplantation embryos were collected and cultured to assess developmental progression, cell number, and chromosomal aberrations.
- Sister chromatid exchange (SCE) frequency was analyzed in embryos exposed on day 2.
Main Results:
- MNU exposure on day 2 led to reduced cell number and increased SCE frequency, but no structural chromosomal aberrations.
- MNU exposure on day 3 resulted in reduced cell numbers, inhibited development, and increased structural chromosomal aberrations.
- High MNU cytotoxicity precluded SCE analysis in day 3 exposed embryos.
Conclusions:
- MNU rapidly reaches preimplantation mouse embryos following maternal administration.
- Observed malformations and postnatal effects are likely due to direct MNU action on early embryos.
- The timing of toxicologic assessment is critical for evaluating preimplantation embryo sensitivity to chemical agents.