This AOP is licensed under a Creative Commons Attribution 4.0 International License.

Aop: 274

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

Histone deacetylase inhibition leads to impeded craniofacial development

Short name

A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help

HDAC inhibition leads to impeded craniofacial development

Graphical Representation

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Authors

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

Bjorn Koch, Annemarie Meijer, Herman Spaink, Thomas Braunbeck

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

Marvin Martens (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

Marvin Martens
Job Berkhout

Status

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Author status	OECD status	OECD project	SAAOP status
Under Development: Contributions and Comments Welcome

This AOP was last modified on January 06, 2022 09:28

Revision dates for related pages

Page	Revision Date/Time
Histone deacetylase inhibition	July 14, 2022 16:18
Neural crest cell migration, reduced	December 20, 2018 04:10
Collagen production, reduced	December 20, 2018 04:15
Facial cartilage structures are reduced in size and morphologically distorted	December 20, 2018 04:16
Histone deacetylase inhibition leads to Reduced neural crest cell migration	December 20, 2018 04:22
Histone deacetylase inhibition leads to Reduced collagen production	December 20, 2018 04:33
Reduced neural crest cell migration leads to Reduced collagen production	December 20, 2018 04:27
Reduced collagen production leads to Smaller and morphologically distorted facial cartilage structures	December 20, 2018 04:30
Valproic acid	December 20, 2018 04:35
Butyrate	January 21, 2018 20:39
Trichostatin A	January 21, 2018 20:39
Suberoylanilide hydroxamic acid	December 20, 2018 04:36
MS-275	December 20, 2018 04:37
Apicidin	December 20, 2018 04:37

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

Histone deacetylases (HDACs) regulate gene expression through modulating chromatin structure and are known to impact many aspects of development in animals. Several compounds have been found to inhibit the action of HDACs leading to various adverse outcomes. This AOP aims to describe the sequence of events by which HDAC inhibition leads to impeded craniofacial development. The MIE is the inhibition, at early embryonic stages, of histone deacetylases. This leads to inhibition of cranial neural crest cell migration and inhibition of chondrocyte differentiation. The attenuation of chondrocyte differentiation reduces the production of collagen, a key structural component of cartilage, resulting in the reduced size and morphologically distorted facial cartilage features. This AOP concerns very specific developmental effects of an MIE which has very broad gene regulatory implications. This means that the progression through KEs and AO are mainly applicable at early developmental stages prior to neural crest migration and chondrocyte differentiation. The AOP is linked to case study 2, concerning the developmental and reproductive toxicity of valproic acid (VPA) and several structural homologs. One of the well-described developmental toxicity effects of fetal VPA exposure is craniofacial deformities.

AOP Development Strategy

Context

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Strategy

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Summary of the AOP

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Events:

Molecular Initiating Events (MIE)

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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

1502

Histone deacetylase inhibition

KE	1557	Neural crest cell migration, reduced	Reduced neural crest cell migration
KE	1558	Collagen production, reduced	Reduced collagen production

1559

Facial cartilage structures are reduced in size and morphologically distorted

Smaller and morphologically distorted facial cartilage structures

Relationships Between Two Key Events (Including MIEs and AOs)

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Title	Adjacency	Evidence	Quantitative Understanding

Histone deacetylase inhibition leads to Reduced neural crest cell migration	adjacent	Not Specified	Not Specified
Reduced neural crest cell migration leads to Reduced collagen production	adjacent	Not Specified	Not Specified
Reduced collagen production leads to Smaller and morphologically distorted facial cartilage structures	adjacent	Not Specified	Not Specified

Histone deacetylase inhibition leads to Reduced collagen production

non-adjacent

Not Specified

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
Valproic acid
Butyrate
Trichostatin A
Suberoylanilide hydroxamic acid
MS-275
Apicidin

Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Known Modulating Factors

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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