Related Experiment Videos
Congenital defects in the offspring of male mice treated with ethylnitrosourea
1Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Abstract:
Daily doses of ENU (25-100 mg/kg) were injected intraperitoneally into ICR strain male mice for 5 days. The males were mated to untreated virgin females of the same strain on days 1-16 and 64-80 after the last dose. Copulations during these periods involve, respectively, treated postmeiotic cells and spermatogonial stem cells. The uterine contents were examined on day 18 of pregnancy for evidence of dominant lethal effects. The fetuses were examined for external and skeletal abnormalities. ENU treatment of either postmeiotic cells or spermatogonial stem cells caused dose-dependent significant increases in the incidence of abnormal fetuses over the control level. The induction rate per live fetus per unit dose in mg/kg by treating spermatogonial stem cells was estimated to be 1.0 X 10(-4), which is 3-fold lower than the rate previously estimated for the same endpoint at the same germ cell stage with MNU. Cleft palate was the most frequent external abnormality in the ENU-treated and the control series. Malformed vertebrae was the most frequent skeletal abnormality in the treated series. Rib fusion was the only skeletal malformation seen in the control series. Dominant lethals were clearly induced when germ cells were treated as postmeiotic cells.
Insights
Ethylnitrosourea (ENU) causes dose-dependent fetal abnormalities in mice, particularly affecting postmeiotic germ cells. This study quanties ENU
Area of Science:
- Toxicology
- Developmental Biology
- Genetics
Background:
- Ethylnitrosourea (ENU) is a potent mutagen used to induce genetic alterations.
- Understanding the effects of ENU on germ cells is crucial for assessing reproductive risks.
Purpose of the Study:
- To evaluate the dominant lethal effects and teratogenicity of ENU in mice.
- To compare the sensitivity of postmeiotic cells and spermatogonial stem cells to ENU-induced mutations.
Main Methods:
- Male ICR mice were administered daily intraperitoneal doses of ENU (25-100 mg/kg) for 5 days.
- Mice were mated with untreated females at different time points to assess effects on postmeiotic cells and spermatogonial stem cells.
- Fetuses were examined for dominant lethal effects and external/skeletal abnormalities.
Main Results:
- ENU treatment induced a dose-dependent increase in fetal abnormalities, affecting both postmeiotic cells and spermatogonial stem cells.
- The induction rate of abnormalities in spermatogonial stem cells was lower compared to N-methyl-N-nitrosourea (MNU).
- Cleft palate and malformed vertebrae were the most frequent abnormalities observed.
Conclusions:
- ENU is a potent inducer of dominant lethals and teratogenic effects in mouse germ cells.
- Postmeiotic germ cells are sensitive to ENU-induced dominant lethality.
- ENU poses a significant risk for reproductive toxicity and developmental abnormalities.