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

The current version of the Developer's Handbook will be automatically populated into the Handbook Version field when a new AOP page is created.Authors have the option to switch to a newer (but not older) Handbook version any time thereafter. More help

Handbook Version v2.0

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

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

Allie Always (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
Allie Always

Coaches

This field is used to identify coaches who supported the development of the AOP.Each coach selected must be a registered author. More help

OECD Information Table

Provides users with information concerning how actively the AOP page is being developed and whether it is part of the OECD Workplan and has been reviewed and/or endorsed. OECD Project: Assigned upon acceptance onto OECD workplan. This project ID is managed and updated (if needed) by the OECD. OECD Status: For AOPs included on the OECD workplan, ‘OECD status’ tracks the level of review/endorsement of the AOP . This designation is managed and updated by the OECD. Journal-format Article: The OECD is developing co-operation with Scientific Journals for the review and publication of AOPs, via the signature of a Memorandum of Understanding. When the scientific review of an AOP is conducted by these Journals, the journal review panel will review the content of the Wiki. In addition, the Journal may ask the AOP authors to develop a separate manuscript (i.e. Journal Format Article) using a format determined by the Journal for Journal publication. In that case, the journal review panel will be required to review both the Wiki content and the Journal Format Article. The Journal will publish the AOP reviewed through the Journal Format Article. OECD iLibrary published version: OECD iLibrary is the online library of the OECD. The version of the AOP that is published there has been endorsed by the OECD. The purpose of publication on iLibrary is to provide a stable version over time, i.e. the version which has been reviewed and revised based on the outcome of the review. AOPs are viewed as living documents and may continue to evolve on the AOP-Wiki after their OECD endorsement and publication. More help

OECD Project #	OECD Status	Reviewer's Reports	Journal-format Article	OECD iLibrary Published Version

This AOP was last modified on May 26, 2024 20:39

Revision dates for related pages

Page	Revision Date/Time
Deposition of Ionizing Energy	December 13, 2021 08:03
Increased, Reactive oxygen species	April 10, 2024 17:33
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	September 14, 2023 12:10
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 Increase, DNA Damage	May 12, 2021 08:40
Ionizing Energy leads to Altered, Meiotic chromosome dynamics	May 14, 2021 04:46
Increased, Reactive oxygen species leads to Increased, Oxidative Stress	July 31, 2023 15:55
Ionizing Energy leads to Decreased spermatogenesis	May 14, 2021 04:46
Increase, DNA Damage leads to Altered, Meiotic chromosome dynamics	May 12, 2021 08:41
Ionizing Energy leads to impaired, Fertility	May 14, 2021 04:47
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
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	1194	Increase, DNA damage	Increase, DNA Damage
KE	406	impaired, Fertility	impaired, Fertility
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

Ionizing Energy leads to Increased, Reactive oxygen species	adjacent	High	High
Ionizing Energy leads to Increase, DNA Damage	adjacent	High	High
Increased, Reactive oxygen species leads to Increased, Oxidative Stress	adjacent	High	High
Increase, DNA Damage leads to Altered, Meiotic chromosome dynamics	adjacent	Moderate	Moderate
Increase, DNA Damage leads to Increase, Oocyte apoptosis	adjacent	High	High
Altered, Meiotic chromosome dynamics leads to Increase, Oocyte apoptosis	adjacent	Moderate	Moderate
Altered, Meiotic chromosome dynamics leads to Decreased spermatogenesis	adjacent	High	High
Increased, Oxidative Stress leads to Increase, Oocyte apoptosis	adjacent	Moderate	Moderate
Increase, DNA Damage leads to Cell cycle, disrupted	adjacent	Moderate	Low
Cell cycle, disrupted leads to Altered, Meiotic chromosome dynamics	adjacent	Low	Low
Increase, Oocyte apoptosis leads to Decrease, Oogenesis	adjacent	Moderate	Low
Increase, Oocyte apoptosis leads to impaired, Fertility	adjacent	High	Moderate
Decreased spermatogenesis leads to impaired, Fertility	adjacent	High	High
Decreased spermatogenesis leads to Decrease of egg production and cummulative fecundity	adjacent	High	High
impaired, Fertility leads to Decrease of egg production and cummulative fecundity	adjacent	High	High
Decrease of egg production and cummulative fecundity leads to Decreased, Population size	adjacent	High	High

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

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

Name
Gamma radiation
Ionizing Radiation

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. 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.