API XML

Aop: 349

AOP Title

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Inhibition of 11β-hydroxylase leading to male infertility in fish

Short name:

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11β-hydroxylase inhibition, male infertility in fish

Graphical Representation

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Click to download graphical representation template

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Authors

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Point of Contact

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Young Jun Kim   (email point of contact)

Contributors

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  • Young Jun Kim

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite


This AOP was last modified on July 21, 2020 09:55

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Revision dates for related pages

Page Revision Date/Time
11β-hydroxylase inhibition July 13, 2020 04:28
Decreased, 11-ketotestosterone May 19, 2020 12:29
Decreased size and sperm volume July 13, 2020 04:32
impaired, Fertility December 02, 2016 09:21
11β-hydroxylase inhibition leads to Decreased, 11KT July 13, 2020 04:34
Decreased, 11KT leads to Decreased size and sperm volume July 21, 2020 09:54
Decreased size and sperm volume leads to impaired, Fertility July 13, 2020 04:42
Metyrapone July 12, 2020 10:26
Lysodren, Mitotan, Mitotane July 12, 2020 10:27
Etomidate July 12, 2020 10:27
Ketoconazole May 02, 2017 11:08
Osilodrostat(LCI699) July 12, 2020 10:30

Abstract

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Cyp11c1 encodes 11βhydroxylase which is one of the critical enzymes mediating the conversion of testosterone to 11-KT, and of 11-deoxycortisol to cortisol in fish. The previous study showed that inhibition of 11βhydroxylase delayed juvenile ovary to testis transition and defective spermatogenesis at adult stage.


Background (optional)

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11βhydroxylase is prominently expressed in the Leydig cells of the testis in teleost.


Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
MIE 1796 11β-hydroxylase inhibition 11β-hydroxylase inhibition
KE 1756 Decreased, 11-ketotestosterone Decreased, 11KT
KE 1798 Decreased size and sperm volume Decreased size and sperm volume
AO 406 impaired, Fertility impaired, Fertility

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
11β-hydroxylase inhibition leads to Decreased, 11KT adjacent High Moderate
Decreased, 11KT leads to Decreased size and sperm volume adjacent Moderate Low
Decreased size and sperm volume leads to impaired, Fertility adjacent High Low

Network View

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Stressors

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Name Evidence Term
Metyrapone High
Lysodren, Mitotan, Mitotane High
Etomidate High
Ketoconazole High
Osilodrostat(LCI699) Moderate

Life Stage Applicability

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Life stage Evidence
Adult, reproductively mature High

Taxonomic Applicability

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Term Scientific Term Evidence Link
fish fish Moderate NCBI

Sex Applicability

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Sex Evidence
Male High

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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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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  1. Zebrafish cyp11c1 Knockout Reveals the Roles of 11-ketotestosterone and Cortisol in Sexual Development and Reproduction. Endocrinology 2020 Jun 1;161(6):bqaa048.
  2. Loss of Cyp11c1 Causes Delayed Spermatogenesis Due to the Absence of 11-ketotestosterone. J Endocrinol 2020 Mar;244(3):487-499.
  3. The Onset of Spermatogenesis in Fish. Ciba Found Symp 1994;182:255-67; discussion 267-70.
  4. Impaired Spermatogenesis in the Japanese Eel, Anguilla Japonica: Possibility of the Existence of Factors That Regulate Entry of Germ Cells Into Meiosis.  Dev Growth Differ 1997 Dec;39(6):685-91
  5. Zebrafish 20β-Hydroxysteroid Dehydrogenase Type 2 Is Important for Glucocorticoid Catabolism in Stress Response PLOS 2013 8 (1) e54851
  6. A newly cyp11c1-GFP transgenic zebrafish model to study corticosteroidogenesis and its perturbation by endocrine active substances at early developmental stages. Conference paper
  7. Large-scale transcriptome sequencing reveals novel expression patterns for key sex-related genes in a sex-changing fish. Biol Sex Differ. 2015; 6: 26.
  8. A Critical Role of Follicle-Stimulating Hormone (Fsh) in Mediating the Effect of Clotrimazole on Testicular Steroidogenesis in Adult Zebrafish. Toxicology 2012 Aug 16;298(1-3):30-9