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Event: 1075

Key Event Title

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

prolonged, estrus cycle

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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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

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
prolonged estrous cycle		increased
prolonged estrus		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
GnRH pulse disruption and mammary tumors.	KeyEvent	Charles Wood (send email)	Under Development: Contributions and Comments Welcome
GnRH pulse disruption and pituitary tumors	KeyEvent	Charles Wood (send email)	Under Development: Contributions and Comments Welcome
Activation, ERα leads to prolonged estrus cycle via decreased kisspeptin	AdverseOutcome	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
mammals	mammals	High	NCBI

Life Stages

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

Life stage	Evidence
Adult, reproductively mature	Moderate

Sex Applicability

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

Term	Evidence
Female	High

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

The estrus cycle is a coordinated series of changes that results in fertility in mammals. Changes to the uterus and vagina are coordinated through hormone signaling, including Progesterone, Estradiol, Luteinizing Hormone, and Follicle-Stimulating Hormone in order to progress through metestrus, diestrus, proestrus, and estrous phases over a period of 4-5 days in rodents (Miller and Takahashi 2014; Swift et al. 2024). In proestrus, increased estradiol levels occur, and physiological changes include ovarian follicle development and the thickening of the uterine wall in preparation for potential pregnancy. In estrus, a surge in luteinizing hormone levels occur, and ovulation of the mature egg. Metestrus is a short transition between estrus and diestrus, features an increase in progesterone levels, and development of the corpus luteum begins in preparation for pregnancy. Diestrus includes continued high levels of progesterone and further development of the corpus luteum; if pregnancy does not occur the corpus luteum regresses and resetting of the cycle occurs. Prolonged estrous occurs when the normal estrus cycle progression has been disrupted.

Length of phases of the estrus cycle (modified from data/format from Ajayi and Akhigbe 2020):

Phase	Length in Rats	Length in Mice
Proestrus	14 hours	<24 hours
Estrus	24-48 hours	12-48 hours
Mestestrus	6-8 hours	8-24 hours
Diestrus	48-72 hours	48-72 hours

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

The phases of the estrus cycles are determined by anatomical changes to the vagina and uterus, as well as vaginal smear/cytology (Laffan et al. 2018; Ajayi and Akhigbe 2020).

Analysis of hormone levels can also be performed but are more labor intensive, more stressful to animals, and less definitive than physical examination.

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: Adult, reproductively mature and juveniles.

Sex: Applies to females.

Taxonomic: Primarily studied in laboratory rodents. Plausible for most mammals due to shared reproductive physiology and hormones. Primates have menstrual cycles as the lining of the uterus is shed rather than being reabsorbed.

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

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

Ajayi, A.F. and Akhigbe, R.E. 2020. Staging of the estrous cycle and induction of estrus in experimental rodents: an update. Fertility Research and Practice 6: 5.

Laffan, S.B., Lorraine M. Posobiec, L.M., Jenny E. Uhl, J.E., and Vidal, J.D. 2018. Species Comparison of Postnatal Development of the Female Reproductive System. Birth Defects Research 110(3): 163-189.

Miller, B.H. and Takahashi, J.S. 2014. Central circadian control of female reproductive function. Frontiers in Endocrinology 4(1): 195.

Swift, K.M., Gary, N.C., and Urbanczyk, P.J. 2024. On the basis of sex and sleep: the influence of the estrous cycle and sex on sleep-wake behavior. Frontiers in Neuroscience 18:1426189.

NOTE: Italics indicate edits from John Frisch October 2025. A full list of updates can be found in the Change Log on the View History page.