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Using Caenorhabditis elegans for Studying Trans- and Multi-Generational Effects of Toxicants
Published on: July 29, 2019
Chemotherapy-induced late transgenerational effects in mice
Loro L Kujjo1, Eun A Chang, Ricardo J G Pereira
1Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
Plos One
|March 26, 2011
Summary
Doxorubicin chemotherapy in female mice caused lasting reproductive and behavioral harm, with effects transmitted across generations, including physical malformations and neonatal death in offspring.
Area of Science:
- Reproductive toxicology
- Developmental toxicology
- Cancer chemotherapy side effects
Background:
- Limited data exists on long-term reproductive and developmental effects of doxorubicin (DXR) in offspring.
- Transgenerational transmission of chemotherapy-induced adverse effects is largely unstudied.
Purpose of the Study:
- To investigate the long-term reproductive and behavioral consequences of doxorubicin exposure in female mice and their progeny.
- To assess the transgenerational inheritance of doxorubicin's detrimental effects through multiple filial generations.
Main Methods:
- Female C57BL/6 mice (Generation 0) received a single intraperitoneal injection of doxorubicin (DXR) or saline.
- Evaluated reproductive parameters, behavioral tests (anxiety, despair, depression), and health of offspring across six generations.
- Conducted detailed analysis of reproductive capacity and physical/chromosomal health in subsequent generations.
Main Results:
- Doxorubicin-treated females exhibited despair-like behaviors, delivery complications, reduced primordial follicles, and early reproductive senescence.
- Transgenerational effects were observed, with significant increases in neonatal death, physical malformations, and chromosomal abnormalities (chromosome 10 deletions) in offspring up to Generation 6.
- Maternal deaths due to delivery complications and severe health issues in offspring were noted in DXR-exposed lineages.
Conclusions:
- Doxorubicin exposure induces persistent, transgenerational reproductive and developmental toxicity in mice, potentially via oocyte genetic alterations or cell death.
- These findings highlight the critical need for long-term monitoring of cancer survivors and their descendants.
- The study underscores the profound and heritable risks associated with doxorubicin treatment, necessitating further investigation into its long-term impact.
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