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Updated: Sep 29, 2026
Comprehensive Assessment of Germline Chemical Toxicity Using the Nematode Caenorhabditis elegans
Published on: February 22, 2015
The effect of tributyltin chloride on Caenorhabditis elegans germline is mediated by a conserved DNA damage
Zhe Cheng1, Huimin Tian2, Hongran Chu1
1State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Abstract:
Tributyltin (TBT), one of the environmental pollutants, has been shown to impact the reproduction of animals. However, due to the lack of appropriate animal model, analysis of the affected molecular pathways in germ cells is lagging and has been particularly challenging. In the present study, we investigated the effects of tributyltin chloride (TBTCL) on the nematode Caenorhabditis elegans germline. We show that exposure of C. elegans to TBTCL causes significantly elevated level of sterility and embryonic lethality. TBTCL exposure results in an increased number of meiotic DNA double-strand breaks in germ cells, subsequently leading to activated DNA damage checkpoint. Exposing C. elegans to TBTCL causes dose- and time-dependent germline apoptosis. This apoptotic response was blocked in loss-of-function mutants of hus-1 (op241), mrt-2 (e2663) and p53/cep-1 (gk138), indicating that checkpoints and p53 are essential for mediating TBTCL-induced germ cell apoptosis. Moreover, TBTCL exposure can inhibit germ cell proliferation, which is also mediated by the conserved checkpoint pathway. We thereby propose that TBT exhibits its effects on the germline by inducing DNA damage and impaired maintenance of genomic integrity.
Insights
Tributyltin (TBT) exposure causes sterility and embryonic lethality in Caenorhabditis elegans by inducing DNA damage in germ cells. This triggers apoptosis and inhibits proliferation, highlighting TBT
Area of Science:
- Environmental Toxicology
- Developmental Biology
- Genetics
Background:
- Tributyltin (TBT) is an environmental pollutant known to disrupt animal reproduction.
- Analyzing TBT's molecular effects on germ cells is challenging due to a lack of suitable animal models.
Purpose of the Study:
- To investigate the impact of tributyltin chloride (TBTCL) on the Caenorhabditis elegans germline.
- To elucidate the molecular pathways involved in TBTCL-induced reproductive toxicity.
Main Methods:
- Exposure of Caenorhabditis elegans to varying doses and durations of TBTCL.
- Analysis of meiotic DNA double-strand breaks, DNA damage checkpoint activation, germline apoptosis, and germ cell proliferation.
- Utilizing loss-of-function mutants for key DNA damage response genes (hus-1, mrt-2, p53/cep-1).
Main Results:
- TBTCL exposure significantly increased sterility and embryonic lethality in C. elegans.
- Increased meiotic DNA double-strand breaks and activated DNA damage checkpoints were observed.
- TBTCL induced dose- and time-dependent germline apoptosis, dependent on hus-1, mrt-2, and p53/cep-1.
- TBTCL inhibited germ cell proliferation via the checkpoint pathway.
Conclusions:
- Tributyltin chloride induces reproductive toxicity in C. elegans by causing DNA damage in germ cells.
- The DNA damage response pathways, including checkpoints and p53, are crucial for mediating TBTCL's effects.
- TBT disrupts germline integrity and reproductive success through genotoxicity.
