Aop: 396

Title

A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE. More help

Deposition of ionizing energy leads to population decline via impaired meiosis

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
Deposition of ionizing energy leads to population decline via impaired meiosis

Graphical Representation

A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs. More help
Click to download graphical representation template Explore AOP in a Third Party Tool
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Authors

The names and affiliations of the individual(s)/organisation(s) that created/developed the AOP. More help

Erica Maremonti 1, Deborah H. Oughton 1, Elizabeth Dufourcq-Sekatcheff 2, Sandrine Frelon 2, Rémi Guédon 2, Catherine Lecomte-Pradines 2, Lisa Magdalena Rossbach 1, Dag Anders Brede 1

1 Centre for Environmental Radioactivity (CERAD), Faculty of Environmental Sciences and Natural ResourceManagement (MINA), Norwegian University of Life Sciences (NMBU), 1432 Ås, Norway

2 Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV, SERIS, Laboratoire d'ECOtoxicologie des radionucléides (LECO), Cadarache, France

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section.   More help
Erica Maremonti   (email point of contact)

Contributors

Users with write access to the AOP page.  Entries in this field are controlled by the Point of Contact. More help
  • Erica Maremonti
  • Dag Anders Brede

Status

Provides users with information concerning how actively the AOP page is being developed, what type of use or input the authors feel comfortable with given the current level of development, and whether it is part of the OECD AOP Development Workplan and has been reviewed and/or endorsed. OECD Status - Tracks the level of review/endorsement the AOP has been subjected to. OECD Project Number - Project number is designated and updated by the OECD. SAAOP Status - Status managed and updated by SAAOP curators. More help
Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite
This AOP was last modified on October 25, 2022 03:57

Revision dates for related pages

Page Revision Date/Time
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
Cell cycle, disrupted June 30, 2021 02:56
Decrease, Oogenesis April 30, 2020 16:41
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 Altered, Meiotic chromosome dynamics May 14, 2021 04:46
Ionizing Energy leads to Increase, DNA Damage May 12, 2021 08:40
Increased, Reactive oxygen species leads to Increased, Oxidative Stress December 03, 2016 16:38
Ionizing Energy leads to Decreased spermatogenesis May 14, 2021 04:46
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
Ionizing Energy leads to Decrease of egg production and cummulative fecundity May 14, 2021 04:48
Increase, DNA Damage leads to Increase, Oocyte apoptosis May 12, 2021 08:42
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
Increase, DNA Damage leads to Cell cycle, disrupted October 25, 2022 03:56
Cell cycle, disrupted leads to Altered, Meiotic chromosome dynamics October 25, 2022 03:56
Increase, Oocyte apoptosis leads to Decrease, Oogenesis April 30, 2020 16:44
Increase, Oocyte apoptosis leads to impaired, Fertility May 12, 2021 08:46
Decreased spermatogenesis leads to impaired, Fertility July 13, 2020 04:42
Decreased spermatogenesis leads to Decrease of egg production and cummulative fecundity May 12, 2021 08:47
impaired, Fertility 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

Abstract

A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance. More help

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.

AOP Development Strategy

Context

Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. More help

Strategy

Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components.  Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used). More help

Summary of the AOP

This section is for information that describes the overall AOP. The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed. More help

Events:

Molecular Initiating Events (MIE)
An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP. More help
Key Events (KE)
A measurable event within a specific biological level of organisation. More help
Adverse Outcomes (AO)
An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help
Type Event ID Title Short name
MIE 1550 Deposition of Ionizing Energy Ionizing Energy
KE 1364 Increase, Reactive oxygen species Increase, ROS
KE 1088 Increased, Oxidative Stress Increased, Oxidative Stress
KE 752 Altered, Meiotic chromosome dynamics Altered, Meiotic chromosome dynamics
KE 1775 Increase, Oocyte apoptosis Increase, Oocyte apoptosis
KE 1115 Increased, Reactive oxygen species Increased, Reactive oxygen species
KE 1798 Decreased spermatogenesis Decreased spermatogenesis
KE 406 impaired, Fertility impaired, Fertility
KE 1194 Increase, DNA damage Increase, DNA Damage
KE 1505 Cell cycle, disrupted Cell cycle, disrupted
KE 1366 Decrease, Oogenesis Decrease, Oogenesis
AO 1696 Decrease of egg production and cummulative fecundity Decrease of egg production and cummulative fecundity
AO 1863 Decrease, Reproduction Decrease, Reproduction
AO 997 Decreased, Population size Decreased, Population size

Relationships Between Two Key Events (Including MIEs and AOs)

This table summarizes all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP.Each table entry acts as a link to the individual KER description page. More help
Title Adjacency Evidence Quantitative Understanding

Network View

This network graphic is automatically generated based on the information provided in the MIE(s), KEs, AO(s), KERs and Weight of Evidence (WoE) summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs. More help

Prototypical Stressors

A structured data field that can be used to identify one or more “prototypical” stressors that act through this AOP. Prototypical stressors are stressors for which responses at multiple key events have been well documented. More help

Life Stage Applicability

The life stage for which the AOP is known to be applicable. More help
Life stage Evidence
Larval development High

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available. More help
Term Scientific Term Evidence Link
Caenorhabditis elegans Caenorhabditis elegans High NCBI

Sex Applicability

The sex for which the AOP is known to be applicable. More help
Sex Evidence
Hermaphrodite High

Overall Assessment of the AOP

Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). More help

Domain of Applicability

Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context. More help

Essentiality of the Key Events

The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs. More help

Evidence Assessment

Addressess the biological plausibility, empirical support, and quantitative understanding from each KER in an AOP. More help

Known Modulating Factors

Modulating factors (MFs) may alter the shape of the response-response function that describes the quantitative relationship between two KES, thus having an impact on the progression of the pathway or the severity of the AO.The evidence supporting the influence of various modulating factors is assembled within the individual KERs. More help

Quantitative Understanding

Optional field to provide quantitative weight of evidence descriptors.  More help

Considerations for Potential Applications of the AOP (optional)

Addressess potential applications of an AOP to support regulatory decision-making.This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. More help

References

List of the literature that was cited for this AOP. More help

Hartman, P. S., & Herman, R. K. (1982). Radiation-sensitive mutants of Caenorhabditis elegans. Genetics102(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 Sciences246(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 Genet5(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 signaling21(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 radioactivity137, 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 genetics14(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 Environment695, 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 medicine152, 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 Safety225, 112793.