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Event: 220

Key Event Title

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

Increase, Plasma vitellogenin concentrations

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
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term
blood plasma

Key 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
	vitellogenins	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
Estrogen receptor agonism leading to reproductive dysfunction	KeyEvent	Undefined (send email)	Under Development: Contributions and Comments Welcome
ER agonism : reduced survival	KeyEvent	Undefined (send email)	Under Development: Contributions and Comments Welcome
ER agonism leads to reduced survival/population growth	KeyEvent	Camille Baettig (send email)	Under development: Not open for comment. Do not cite
ER agonism leads to reduced fecundity	KeyEvent	Jason M. O'Brien (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

Life Stages

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

Sex Applicability

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

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

Vitellogenins are large serum phospholipoglycoprotein that are encoded by a family of paralog genes whose number varies in the different vertebrate lineages resulting in numerous isoforms (Wahli, 1988). Vtg is synthesized in the liver and is secreted into the blood as ~500 kDa homodimers which circulate to the ovaries for uptake and bind to receptors on the surface of growing oocytes (Wallace, 1985).

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

Vitellogenin concentrations in plasma are typically measured using enzyme linked immunosorbent assay (ELISA; e.g., Denslow et al., 1999; Holbech et al., 2001). Less specific and/or sensitive assays such as determination of alkali-labile phosphoprotein (e.g., Kramer et al., 1998) and Western blotting (e.g., Heppell et al., 1995) may also be used.

There are also several standardized test guidelines that measure vtg including: Fish Short Term Reproduction Assay (OECD, 2009a), 21-day Fish Assay (OECD, 2009b); Fish Sexual Development Test (OECD, 2011), Medaka Extended One Generation Reproduction Test (OECD, 2015a). Measurement of vtg is also an optional parameter in the Larval Amphibian Growth and Development Assay (OECD, 2015b). The US Environmental Protection Agency (EPA) has similar standardized guidelines (US EPA, 2009, US EPA, 2014) as does the EU as part of the Guidance For The Identification Of Endocrine Disruptors In The Context Of Regulations (EC 2013, EC 2018).

Domain of Applicability

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

Taxonomic applicability: Oviparous vertebrates synthesize yolk precursor proteins that are transported in the circulation for uptake by developing oocytes. Many invertebrates also synthesize vitellogenins that are taken up into developing oocytes via active transport mechanisms. However, invertebrate vitellogenins are transported in hemolymph or via other transport mechanisms rather than plasma.

Life stage: This KE is applicable to all life stages following the differentiation of the liver. Embryos prior to liver differentiation should not be included.

Sex: This KE is applicable to both sexes.

References

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

Denslow, N. D., Chow, M. C., Kroll, K. J., & Green, L. (1999). Vitellogenin as a biomarker of exposure for estrogen or estrogen mimics. Ecotoxicology, 8, 385-398.
Heppell, S. A., Denslow, N. D., Folmar, L. C., & Sullivan, C. V. (1995). Universal assay of vitellogenin as a biomarker for environmental estrogens. Environmental Health Perspectives, 103(suppl 7), 9-15.
Holbech, H., Andersen, L., Petersen, G. I., Korsgaard, B., Pedersen, K. L., & Bjerregaard, P. (2001). Development of an ELISA for vitellogenin in whole body homogenate of zebrafish (Danio rerio). Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 130(1), 119-131.
Kramer, V., Miles-Richardson, S., Pierens, S., & Giesy, J. (1998). Reproductive impairment and induction of alkaline-labile phosphate, a biomarker of estrogen exposure, in fathead minnows (Pimephales promelas) exposed to waterborne 17β-estradiol. Aquatic Toxicology, 40(4), 335-360.
Wahli, W. (1988). Evolution and expression of vitellogenin genes. Trends in Genetics, 4(8), 227-232.
Wallace, R. A. (1985). Vitellogenesis and oocyte growth in nonmammalian vertebrates. Oogenesis, 127-177.