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Teratogen-induced eye defects mediated by p53-dependent apoptosis
J A Wubah1, M M Ibrahim, X Gao
1Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Current Biology : CB
|January 1, 1996
Summary
Environmental stress can cause birth defects through p53-dependent apoptosis. This study shows that genotoxic stress in mouse embryos leads to p53-mediated cell death and congenital eye defects, particularly in wild-type embryos.
Area of Science:
- Developmental biology
- Genetics
- Toxicology
Background:
- Gene-environment interactions are implicated in many birth defects.
- Apoptosis (programmed cell death) is a key cellular response to embryonic stress.
- The p53 tumor suppressor gene regulates apoptosis in response to environmental factors.
Purpose of the Study:
- To investigate the link between p53-dependent apoptosis and teratogenesis (birth defect development).
- To determine if p53 gene status influences susceptibility to teratogen-induced birth defects.
Main Methods:
- Day 8 mouse embryos with varying p53 gene backgrounds were exposed to the genotoxic stressor 2-chloro-2'-deoxyadenosine.
- Nuclear p53 accumulation, apoptosis, and embryonic development were assessed.
- Incidences of abnormal development, specifically eye defects, were recorded at term.
Main Results:
- Genotoxic stress induced p53 accumulation and apoptosis in a p53 gene-dose-dependent manner.
- Wild-type embryos showed higher rates of apoptosis and subsequent eye defects (73.3%) compared to heterozygous (52.5%) and p53-null mutants (2.2%).
- A significant interaction (P < 0.001) was observed between the teratogen and genotype for both cell death and eye defects.
Conclusions:
- Teratogen-induced apoptosis regulated by the p53 gene is directly linked to the development of congenital eye defects.
- p53 plays a critical role in mediating the embryonic response to genotoxic stress, influencing teratogenesis.