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Key Event: 2417

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased, differentiation to ovaries

Short name

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Individual

Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
female gonad development	immature gonad	increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Activation, ERα leads to female-biased sex ratio via increased, differentiation to ovaries	KeyEvent	John Frisch (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
Animals	Metazoa	Moderate	NCBI
fish	fish	High	NCBI
Amphibia	Amphibia	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Development	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Female	High
Mixed	Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Ovaries are female organs responsible for producing eggs and secreting hormones that regulate development and reproduction.

Although the relative importance of genetic and environmental factors for determining the sex of an individual differ among classes of vertebrates, there are some evolutionarily conserved consistencies in development (Ditewig and Yao, 2005; Nichol et al., 2022). The gonadal primordium (genital ridge) develops on the surface of the mesonephros (intermediate mesoderm), which has the capability to develop either into ovaries or testes. Upon receiving genetic and/or environmental cues to undergo female development, cells from the gonadal primordium differentiate into granulosa cells. Subsequent differentiation results in increased specialization of cells in the developing ovary, including germ cells (follicles that develop into oocytes) and somatic cells (granulosa and thecal cells that produce hormones among other duties, stromal cells that provide connective tissue, epithelium surface cells).

In species with genetic sex determination (GSD) whether an organism develops into a male or female is based on chromosome composition (in vertebrates mammals and birds per Nagahama et al., 2021). In species with environmental sex determination (ESD), environmental factors such as temperature influence whether an organism develops into a male or female (in vertebrates, mainly amphibians, fish and reptiles per Nagahama et al., 2021). For a review of sex determination systems in invertebrates, see (Picard et al., 2021).

In fish husbandry, long-standing practice has demonstrated that adding estrogens during development can increase the number of individuals that develop ovaries, of interest when females achieve greater growth than males (in many fish species per review by Piferrer, 2001). Similarly exposure to endocrine disrupting compounds during development can result in an increased number of fish that develop ovaries as seen in sex ratios (in many fish species per review by Dang and Kienzler, 2019). In fish estrogens have a central role in pathways leading to ovarian differentiation, with androgens causing testicular differentiation (Guiguen et al., 2010).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Verification of sex is done by histological examination of reproductive organs.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Life Stage: Development.

Sex: Applies to females, with some mixed genders observed.

Taxonomic: Largely studied in vertebrates, with some research in sexually reproducing invertebrate. Vertebrates differ in prevalence of environmental sex determination (Nagahama et al., 2021), with amphibians, reptiles and fish most likely to have increased differentiation to ovaries from environmental factors.

References

List of the literature that was cited for this KE description. More help

Dang Z, Kienzler A. 2019. Changes in fish sex ratio as a basis for regulating endocrine disruptors. Environment International 130: 104928.

Ditewig AC, Yao HH. 2005. Organogenesis of the ovary: a comparative review on vertebrate ovary formation. Organogenesis 2(2): 36-41.

Guiguen Y, Fostier A, Piferrer F, Chang CF. 2010. Ovarian aromatase and estrogens: a pivotal role for gonadal sex differentiation and sex change in fish. General and Comparative Endocrinology 165(3): 352-366.

Nagahama Y, Chakraborty T, Paul-Prasanth B, Ohta K, Nakamura M. 2021. Sex determination, gonadal sex differentiation, and plasticity in vertebrate species. Physiological Reviews 101(3): 1237-1308.

Nicol B, Estermann MA, Yao HH, Mellouk N. 2022. Becoming female: Ovarian differentiation from an evolutionary perspective. Frontiers in Cell and Development Biology 10: 944776.

Picard MAL, Vicoso B, Bertrand S, Escriva H. 2021. Diversity of Modes of Reproduction and Sex Determination Systems in Invertebrates, and the Putative Contribution of Genetic Conflict. Genes 12(8): 1136.

Piferrer F. 2001. Endocrine sex control strategies for the feminization of teleost fish. Aquaculture 197: 229–281.

NOTE: Italics indicate edits from John Frisch April 2026. A full list of updates can be found in the Change Log on the View History page.