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Developmental toxicity and teratogenicity of trichosanthin, a ribosome-inactivating protein, in mice
1Department of Anatomy, Faculty of Medicine, Chinese University of Hong Kong.
Abstract:
The embryotoxic and teratogenic effects of trichosanthin (TCS), a protein isolated from tubers of Trichosanthes kirilowii (family Cucurbitaceae), were studied both in vivo and in vitro. The protein was administered i.p. to ICR mice on day 8.0 of pregnancy, and the animals were sacrificed 1 day before parturition. The fetuses were fixed and subsequently sectioned. At the highest TCS dose employed (7.5 mg/kg body weight), the viability of fetuses declined to 70.2%, compared with 96.5% in the saline-treated control group. The number of resorbed fetuses increased, and the crown-rump length of the surviving fetuses was reduced. At the doses of 5.0 and 7.5 mg TCS/kg body weight, 2.3% and 9.0%, respectively, of the surviving fetuses were found to be abnormal. The abnormalities observed included exencephaly, micromelia, and short tail. When mouse embryos at the early organogenesis stage were cultured with TCS at a dose of 200 micrograms/ml or above, a significantly larger number of embryos were found to be abnormal as compared with the controls. The abnormalities were observed in the head, trunk, and limb regions. Hence, TCS produced adverse effects on prenatal development both in vivo and in vitro.
Insights
Trichosanthin (TCS) exposure in pregnant mice and in vitro embryo cultures caused significant developmental abnormalities. This protein from Trichosanthes kirilowii negatively impacts fetal viability and causes birth defects.
Area of Science:
- Reproductive Toxicology
- Developmental Biology
- Pharmacology
Background:
- Trichosanthin (TCS) is a protein derived from Trichosanthes kirilowii.
- Understanding the reproductive safety of natural compounds is crucial.
Purpose of the Study:
- To investigate the embryotoxic and teratogenic potential of trichosanthin (TCS).
- To assess the effects of TCS on prenatal development in vivo and in vitro.
Main Methods:
- In vivo studies involved intraperitoneal administration of TCS to pregnant ICR mice on day 8.0 of gestation.
- In vitro studies utilized early organogenesis stage mouse embryos cultured with varying concentrations of TCS.
- Fetal viability, crown-rump length, resorptions, and external abnormalities were assessed.
Main Results:
- TCS administration reduced fetal viability and crown-rump length, and increased resorptions in a dose-dependent manner.
- Abnormalities including exencephaly, micromelia, and short tail were observed in surviving fetuses at higher TCS doses.
- In vitro, TCS exposure led to a significant increase in embryonic abnormalities affecting head, trunk, and limb development.
Conclusions:
- Trichosanthin (TCS) exhibits significant embryotoxic and teratogenic effects.
- TCS adversely impacts prenatal development through both in vivo and in vitro exposure routes.
- Further research is warranted to understand the mechanisms and clinical implications of TCS teratogenicity.