API

Aop: 124

AOP Title

?


HMG-CoA reductase inhibition leading to decreased fertility

Short name:

?

HMGCR inhibition to male fertility

Authors

?


Kellie Fay

Point of Contact

?


Kellie Fay

Contributors

?


  • Kellie Fay

Status

?

Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development 1.29 Included in OECD Work Plan


This AOP was last modified on December 03, 2016 16:37

?

Revision dates for related pages

Page Revision Date/Time
Inhibition, HMG-CoA reductase December 03, 2016 16:33
Decreased, mevalonate December 03, 2016 16:37
Decreased, cholesterol December 03, 2016 16:37
Decreased, Testosterone December 03, 2016 16:37
malformed, Male reproductive tract September 16, 2017 10:16
Decrease, Fertility June 29, 2017 08:09
Inhibition, HMG-CoA reductase leads to Decreased, mevalonate December 03, 2016 16:38
Decreased, mevalonate leads to Decreased, cholesterol December 03, 2016 16:38
Decreased, cholesterol leads to Decreased, Testosterone December 03, 2016 16:38
Decreased, Testosterone leads to malformed, Male reproductive tract December 03, 2016 16:38
malformed, Male reproductive tract leads to Decrease, Fertility December 03, 2016 16:38

Abstract

?


During sexual differentiation and gonadal development in utero or in ovo, androgenic tissues develop, in part, under the control of testosterone (Viger et al. 2005). Reduction of circulating testosterone during this crucial time of development can result in malformed reproductive tracts in males. Exposure to drugs (e.g., statins) or other compounds may cause male reproductive tract abnormalities by inhibiting HMG-CoA reductase, which is the rate-limiting enzyme in the production of cholesteron, the precursor of testosterone.


Background (optional)

?



Summary of the AOP

?



Stressors

?


Molecular Initiating Event

?

Title Short name
Inhibition, HMG-CoA reductase Inhibition, HMG-CoA reductase

Key Events

?

Title Short name
Decreased, mevalonate Decreased, mevalonate
Decreased, cholesterol Decreased, cholesterol
Decreased, Testosterone Decreased, Testosterone
malformed, Male reproductive tract malformed, Male reproductive tract

Adverse Outcome

?

Title Short name
Decrease, Fertility Decrease, Fertility

Relationships Between Two Key Events (Including MIEs and AOs)

?

Network View

?

 

Life Stage Applicability

?

Life stage Evidence
Fetal Weak

Taxonomic Applicability

?

Term Scientific Term Evidence Link
Rattus rattus Rattus rattus NCBI

Sex Applicability

?

Sex Evidence
Male

Graphical Representation

?

Click to download graphical representation template

Overall Assessment of the AOP

?



This AOP was developed primarily from one study of exposure of rats in utero to simvastatin (as well as a phthalate ester; Beverley et al., 2015) and biological plausibility. It currently should be considered putative and untested.

Domain of Applicability

?


Essentiality of the Key Events

?


Weight of Evidence Summary

?


Quantitative Considerations

?


Considerations for Potential Applications of the AOP (optional)

?



References

?


Beverly, B. E. J., et al. (2014). "Simvastatin and Dipentyl Phthalate Lower Ex Vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat." Toxicological Sciences.