Aop:153

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Status

This is a legacy representation of this AOP. Please see the current version here:

https://aopwiki.org/aops/153


AOP Title

Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats
Short name: Aromatase Inhibition in Female Rats

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Status

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Under development: Do not distribute or cite.

This AOP page was last modified on 12/11/2016.

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Abstract

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Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Chemical exposure during critical window of estrous cycle between diestrus 2 and proestrus inhibits aromatase conversion of testosterone to estradiol, Inhibition of Aromatase Enzyme Moderate

Key Events

Event Support for Essentiality
Reduced steroidogenic production of estradiol in granulosa cells, reduction in ovarian granulosa cells synthesis of estradiol Moderate
Reduced steroidogenic production of estradiol in granulosa cells leading to decreased estradiol in circulation, Reduced Estradiol in Circulation Moderate
Reduced estradiol in circulation decreases estrogen concentration at hypothalamus, Decreased positive estrogenic feedback on hypothalamus Moderate
Decreased hypothalamic estrogen reduces kisspeptinergic neuron response , Decreased Kisspeptin release from neurons in AVPV Moderate
Decreased Kisspeptin stimulation of GnRH neurons , Decreased GnRH Release Moderate
Decreased GnRH stimulation of Anterior Pituitary Gonadotrophs, Decreased LH release from Anterior Pituitary Moderate
Decrease or delay in LH surge required for ovulation , Ovulation of oocytes Reduced, Delayed, or Blocked Moderate

Adverse Outcome

Adverse Outcome
Reduced number of oocytes ovulated , Decreased fertility

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Weight of Evidence Summary

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Quantitative Considerations

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References