API

Relationship: 2144

Title

?

Inhibition, Aromatase leads to Reduction, E2 Synthesis by the undifferentiated gonad

Upstream event

?

Inhibition, Aromatase

Downstream event

?


Reduction, E2 Synthesis by the undifferentiated gonad

Key Event Relationship Overview

?


AOPs Referencing Relationship

?

AOP Name Adjacency Weight of Evidence Quantitative Understanding
Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation adjacent High

Taxonomic Applicability

?

Term Scientific Term Evidence Link
Oreochromis niloticus Oreochromis niloticus Low NCBI
zebrafish Danio rerio Moderate NCBI

Sex Applicability

?

Sex Evidence
Unspecific Moderate

Life Stage Applicability

?

Key Event Relationship Description

?


Evidence Supporting this KER

?


Biological Plausibility

?

Empirical Evidence

?

  • Tilapia (Oreochromis niloticus) reared at the standard 27°C showed that genetic males exhibited lower levels of aromatase gene expression and estradiol quantities during the critical period of sexual differentiation(18-26 days post fertilization) whereas a strong expression was detected for all genetic females for both aromatase gene expression and estradiol quantities. This correlation suggests that aromatase repression at the onset of sexual differentiation greatly reduces the biosynthesis of estradiol in the undifferentiated gonad. (D'Cotta et al., 2001)
  • Generation of cyp19a1a and cyp19a1b gene mutant lines and a cyp19a1a;cyp19a1b double knockout line in zebrafish using transcription activator like effector nucleases (TALENs) showed that in both cyp19a1a-deficient and double knockout fish, the levels of estradiol were significantly lower than that in wild-type and cyp19a1b-deficient fish. 8
  • Control XY and cyp19a1a -/- (deficient and double knockout) XX nile tilapia fish had significantly lower levels of serum E2 when compared to the control XX and cyp19a1a+/- XX fish suggesting a decrease in E2 due to the cyp19a1a deficiency. 12

Uncertainties and Inconsistencies

?

Quantitative Understanding of the Linkage

?


Response-response Relationship

?

Time-scale

?

Known modulating factors

?

Known Feedforward/Feedback loops influencing this KER

?

Domain of Applicability

?


Life Stage

The life stage applicable to this key event relationship is developing embryos and juveniles prior to or during the gonadal developmental stage. This key event relationship is not applicable to sexually differentiated adults. 

 

Taxonomic Applicability 

Phylogenetic analysis among mammalian, amphibian, reptile, bird, and fish has shown that aromatase is well conserved among all vertebrates (Wilson JY et al., 2005)70. Additionally, CYP19 was detected in the amphioxus suggesting that it has possible origin in primitive chordates. However this key event is only applicable to to vertebrates. 

References

?