This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Deposition of ionizing energy leads to population decline via impaired meiosis
Point of Contact
- Erica Maremonti
- Dag Anders Brede
|Author status||OECD status||OECD project||SAAOP status|
|Under development: Not open for comment. Do not cite|
This AOP was last modified on December 13, 2021 09:12
|Deposition of Ionizing Energy||December 13, 2021 08:03|
|Increased, Reactive oxygen species||November 27, 2017 13:15|
|Increase, DNA damage||May 08, 2019 12:28|
|Increased, Oxidative Stress||February 03, 2022 14:20|
|Altered, Meiotic chromosome dynamics||May 27, 2019 14:17|
|Increase, Oocyte apoptosis||April 30, 2020 16:41|
|Decreased spermatogenesis||February 09, 2021 08:36|
|impaired, Fertility||December 02, 2016 09:21|
|Decrease of egg production and cummulative fecundity||October 03, 2019 11:13|
|Decreased, Population size||December 03, 2016 16:37|
|Increase, Reactive oxygen species||March 19, 2019 09:41|
|Decrease, Reproduction||April 11, 2021 17:38|
|Ionizing Energy leads to Increased, Reactive oxygen species||May 12, 2021 08:39|
|Ionizing Energy leads to Increased, Oxidative Stress||May 12, 2021 09:16|
|Ionizing Energy leads to Increase, Oocyte apoptosis||May 14, 2021 04:49|
|Increase, Oocyte apoptosis leads to Decrease of egg production and cummulative fecundity||May 18, 2021 07:30|
|Ionizing Energy leads to Increase, DNA Damage||May 12, 2021 08:40|
|Ionizing Energy leads to Altered, Meiotic chromosome dynamics||May 14, 2021 04:46|
|Ionizing Energy leads to Decreased spermatogenesis||May 14, 2021 04:46|
|Increased, Reactive oxygen species leads to Increased, Oxidative Stress||December 03, 2016 16:38|
|Ionizing Energy leads to impaired, Fertility||May 14, 2021 04:47|
|Increase, DNA Damage leads to Altered, Meiotic chromosome dynamics||May 12, 2021 08:41|
|Increase, DNA Damage leads to Increase, Oocyte apoptosis||May 12, 2021 08:42|
|Ionizing Energy leads to Decrease of egg production and cummulative fecundity||May 14, 2021 04:48|
|Ionizing Energy leads to Decreased, Population size||May 14, 2021 04:48|
|Altered, Meiotic chromosome dynamics leads to Increase, Oocyte apoptosis||May 12, 2021 08:42|
|Altered, Meiotic chromosome dynamics leads to Decreased spermatogenesis||May 12, 2021 08:43|
|Increased, Oxidative Stress leads to Increase, Oocyte apoptosis||May 12, 2021 08:44|
|Decreased spermatogenesis leads to impaired, Fertility||July 13, 2020 04:42|
|Increase, Oocyte apoptosis leads to impaired, Fertility||May 12, 2021 08:46|
|impaired, Fertility leads to Decrease of egg production and cummulative fecundity||May 12, 2021 08:47|
|Decreased spermatogenesis leads to Decrease of egg production and cummulative fecundity||May 12, 2021 08:47|
|Decrease of egg production and cummulative fecundity leads to Decreased, Population size||May 12, 2021 08:48|
|Gamma radiation||April 15, 2017 16:04|
|Ionizing Radiation||May 07, 2019 12:12|
Despite the tolerance demonstrated under exposure to high acute doses (> 1 kGy) of ionizing radiation in the nematode Caenorhabditis elegans, adverse outcome at the reproductive level have been observed under exposure of early stages of larval development to low-medium chronic doses (≥ 2.8 Gy). L1-L4 larval stages were shown to be the most radiosensitive stages of development due to adverse effects on gamete production. Specifically, significant sperm reduction and dysregulation of genes related to sperm meiosis and maturation were identified as the main key events (KE1, KE2) causing reduced number of progeny (AO1). Adverse effects of ionizing radiation on proliferative cells were also shown by enhanced germ cell apoptosis (KE3, KE4) in F0 nematodes and significant DNA damage in embryonic cells (F1) of irradiated nematodes, which was corroborated by the dysregulation of genes related to cell-cycle checkpoints, DNA repair, embryonic and post-embryonic development. Increased ROS levels (MIE2) and AODs activation were measured in vivo and by gene expression analysis after chronic irradiation of F0 nematodes. This was not accompanied by any adverse effect on somatic cell viability or any visible phenotypical effect, indicating tolerance of somatic tissue compared to the observed adverse effects shown on the germ cells. The observed redox imbalance suggested a significant contribution of indirect effects, including oxidative damage to DNA (MIE3), and represented the molecular initiating event derived from ionization and excitation of atoms and molecules (MIE1) after chronic irradiation.
Summary of the AOP
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
|Sequence||Type||Event ID||Title||Short name|
|1||MIE||1550||Deposition of Ionizing Energy||Ionizing Energy|
|2||MIE||1115||Increased, Reactive oxygen species||Increased, Reactive oxygen species|
|3||MIE||1194||Increase, DNA damage||Increase, DNA Damage|
|4||KE||1364||Increase, Reactive oxygen species||Increase, ROS|
|5||KE||1088||Increased, Oxidative Stress||Increased, Oxidative Stress|
|6||KE||752||Altered, Meiotic chromosome dynamics||Altered, Meiotic chromosome dynamics|
|7||KE||1775||Increase, Oocyte apoptosis||Increase, Oocyte apoptosis|
|8||KE||1798||Decreased spermatogenesis||Decreased spermatogenesis|
|9||KE||406||impaired, Fertility||impaired, Fertility|
|10||AO||1696||Decrease of egg production and cummulative fecundity||Decrease of egg production and cummulative fecundity|
|11||AO||1863||Decrease, Reproduction||Decrease, Reproduction|
|12||AO||997||Decreased, Population size||Decreased, Population size|
Relationships Between Two Key Events (Including MIEs and AOs)
|Ionizing Energy leads to Increased, Oxidative Stress||non-adjacent||High||High|
|Ionizing Energy leads to Increase, Oocyte apoptosis||non-adjacent||Moderate||Moderate|
|Increase, Oocyte apoptosis leads to Decrease of egg production and cummulative fecundity||non-adjacent||Moderate||Moderate|
|Ionizing Energy leads to Altered, Meiotic chromosome dynamics||non-adjacent||Moderate||Moderate|
|Ionizing Energy leads to Decreased spermatogenesis||non-adjacent||Moderate||Moderate|
|Ionizing Energy leads to impaired, Fertility||non-adjacent||Moderate||Moderate|
|Ionizing Energy leads to Decrease of egg production and cummulative fecundity||non-adjacent||Moderate||Moderate|
|Ionizing Energy leads to Decreased, Population size||non-adjacent||Moderate||Moderate|
Life Stage Applicability
|Caenorhabditis elegans||Caenorhabditis elegans||High||NCBI|
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Considerations for Potential Applications of the AOP (optional)
Hartman, P. S., & Herman, R. K. (1982). Radiation-sensitive mutants of Caenorhabditis elegans. Genetics, 102(2), 159-178.
Hodgkin, J., & Barnes, T. M. (1991). More is not better: brood size and population growth in a self-fertilizing nematode. Proceedings of the Royal Society of London. Series B: Biological Sciences, 246(1315), 19-24.
Shakes, D. C., Wu, J. C., Sadler, P. L., LaPrade, K., Moore, L. L., Noritake, A., & Chu, D. S. (2009). Spermatogenesis-specific features of the meiotic program in Caenorhabditis elegans. PLoS Genet, 5(8), e1000611.
Reisz, J. A., Bansal, N., Qian, J., Zhao, W., & Furdui, C. M. (2014). Effects of ionizing radiation on biological molecules—mechanisms of damage and emerging methods of detection. Antioxidants & redox signaling, 21(2), 260-292.
Buisset-Goussen, A., Goussen, B., Della-Vedova, C., Galas, S., Adam-Guillermin, C., & Lecomte-Pradines, C. (2014). Effects of chronic gamma irradiation: a multigenerational study using Caenorhabditis elegans. Journal of environmental radioactivity, 137, 190-197.
Engert, C. G., Droste, R., van Oudenaarden, A., & Horvitz, H. R. (2018). A Caenorhabditis elegans protein with a PRDM9-like SET domain localizes to chromatin-associated foci and promotes spermatocyte gene expression, sperm production and fertility. PLoS genetics, 14(4), e1007295.
Maremonti, E., Eide, D. M., Oughton, D. H., Salbu, B., Grammes, F., Kassaye, Y. A., ... & Brede, D. A. (2019). Gamma radiation induces life stage-dependent reprotoxicity in Caenorhabditis elegans via impairment of spermatogenesis. Science of the Total Environment, 695, 133835.
Maremonti, E., Eide, D. M., Rossbach, L. M., Lind, O. C., Salbu, B., & Brede, D. A. (2020). In vivo assessment of reactive oxygen species production and oxidative stress effects induced by chronic exposure to gamma radiation in Caenorhabditis elegans. Free radical biology and medicine, 152, 583-596.
Guédon, R., Maremonti, E., Armant, O., Galas, S., Brede, D. A., & Lecomte-Pradines, C. (2021). A systems biology analysis of reproductive toxicity effects induced by multigenerational exposure to ionizing radiation in C. elegans. Ecotoxicology and Environmental Safety, 225, 112793.