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AOP: 619
Title
Androgen receptor antagonism leads to delayed preputial seperation via reduced fibroblast growth factor in genital-tubercle tissues
Short name
Graphical Representation
Point of Contact
Contributors
- Travis Karschnik
Coaches
OECD Information Table
| OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
|---|---|---|---|---|
This AOP was last modified on December 16, 2025 14:58
Revision dates for related pages
| Page | Revision Date/Time |
|---|---|
| Antagonism, Androgen receptor | April 05, 2024 08:04 |
| Androgen receptor nuclear transcriptional activity in genital-tubercle tissues, reduced | December 18, 2025 11:35 |
| Fibroblast growth factor 10, fibroblast growth factor receptor 2 isoform IIIb signaling in genital tissue, reduced | December 18, 2025 11:43 |
| Preputial epithelial morphogenesis, disrupted | December 18, 2025 15:33 |
| Male preputial separation, failed/delayed | February 06, 2026 16:55 |
| Antagonism, Androgen receptor leads to AR transcriptional activity in GT tissues, reduced | February 06, 2026 17:10 |
| AR transcriptional activity in GT tissues, reduced leads to FGF10/FGFR2-IIIb signaling in genital tissue, reduced | December 16, 2025 14:54 |
| FGF10/FGFR2-IIIb signaling in genital tissue, reduced leads to Preputial epithelial morphogenesis, disrupted | December 16, 2025 14:54 |
| Preputial epithelial morphogenesis, disrupted leads to Male PPS, failed/delayed | December 16, 2025 14:55 |
Abstract
AOP Development Strategy
Context
This AOP was as part of an Environmental Protection Agency effort to develop AOPs that establish scientifically supported causal linkages between alternative endpoints measured using new approach methodologies (NAMs) and guideline apical endpoints measured in Tier 1 and Tier 2 test guidelines (U.S. EPA, 2024) employed by the Endocrine Disruptor Screening Program (EDSP). A series of key events that represent significant, measurable, milestones connecting molecular initiation to apical endpoints indicative of adversity were identified based on scientific review articles and empirical studies. Additionally, scientific evidence supporting the causal relationships between each pair of key events was assembled and evaluated.
Strategy
The scope of the aforementioned EPA project was to develop AOP(s) relevant to apical endpoints observed in the test guidelines, based on mechanisms consistent with empirical studies. The literature used to support this AOP and its constituent pages began with the test guidelines and followed to primary, secondary, and/or tertiary works concerning the relevant underlying biology. KE and KER page creation and re-use was determined using Handbook principles where page re-use was preferred.
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
| Type | Event ID | Title | Short name |
|---|
| MIE | 26 | Antagonism, Androgen receptor | Antagonism, Androgen receptor |
| KE | 2393 | Androgen receptor nuclear transcriptional activity in genital-tubercle tissues, reduced | AR transcriptional activity in GT tissues, reduced |
| KE | 2399 | Fibroblast growth factor 10, fibroblast growth factor receptor 2 isoform IIIb signaling in genital tissue, reduced | FGF10/FGFR2-IIIb signaling in genital tissue, reduced |
| KE | 2400 | Preputial epithelial morphogenesis, disrupted | Preputial epithelial morphogenesis, disrupted |
| AO | 2401 | Male preputial separation, failed/delayed | Male PPS, failed/delayed |
Relationships Between Two Key Events (Including MIEs and AOs)
| Title | Adjacency | Evidence | Quantitative Understanding |
|---|
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
| Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
|---|---|---|