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Key Event Title
Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
|Level of Biological Organization|
|primordial germ cell|
Key Event Components
|estrogen biosynthetic process||17beta-estradiol||decreased|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation||KeyEvent||Kelvin Santana Rodriguez (send email)||Under Development: Contributions and Comments Welcome||WPHA/WNT Endorsed|
Key Event Description
Estrogens are essential for normal ovarian differentiation, growth and maintenance. When estrogens bind to estrogen receptors (ER), these then regulate the transcription of downstream estrogen-responsive genes necessary for proper gonad development (Guiguen et al. 2010; Gorelick et al. 2011). Among the different forms of estrogens, 17β-estradiol (E2) is considered the most fundamental in gonad differentiation in most vertebrates, as it is responsible for inducing and maintaining ovarian development (Bondesson et al. 2015; Li et al. 2019). Consequently, disruption of the E2 synthesis by the undifferentiated gonad has been linked to altered gonad differentiation and development in many vertebrates.
How It Is Measured or Detected
Estrogen concentrations can be measured via radioimmunoassay (e.g., US EPA 2002) or by analytical methods such as LC/MS/MS (e.g., Gravitte et al. 2021; Jalabert et al. 2021; Nouri et al. 2020). Measurement in the undifferentiated gonad would generally require extraction of tissue homogenates. This tissue mass can be very limited during primordial stages.
Domain of Applicability
Taxonomic applicability: Most of the key enzymes involved in the process of E2 biosynthesis are well conserved among vertebrates (Callard et al. 2001; Thornton et al. 2001; Eick et al. 2011; Coumailleau et al. 2015). Estrogens play a key role in embryonic development particularly during gonadogenesis for most vertebrates (Coumailleauet al., 2015; Callard et al., 2015). Therefore, it is possible that this key event is applicable to most vertebrate taxa. In contrast, this key event is not applicable to organisms that lack the necessary enzymes for estrogen synthesis such as invertebrates and plants (Jones et al. 2017).
Life stage applicability: Endogenous steroid biosynthesis generally begins shortly after birth or hatch.
Sex applicability: This key event applies to the undifferentiated gonad. Therefore, sex is non-specific.
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