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Event: 1791

Key Event Title

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

Increased, Male Biased Sex Ratio

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
Increased, Male Biased Sex Ratio
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Biological Context

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Level of Biological Organization

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; 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
male sex differentiation population of organisms 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
Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation KeyEvent Brendan Ferreri-Hanberry (send email) Under Development: Contributions and Comments Welcome WPHA/WNT Endorsed
AR agonism leading to male-biased sex ratio KeyEvent Evgeniia Kazymova (send email) Open for citation & comment WPHA/WNT Endorsed

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
Life stage Evidence
Adults High

Sex Applicability

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

Sex ratio is the ratio of males to females in a population. A male-biased sex ratio for a given species is defined as a significant increase in the number of males, relative to the average ratio found in most populations of that species.

While simple in concept, the “normal” sex ratio for a given species can be challenging to define.

  • In organisms with genetic sex determination (GSD) such as mammals and birds, as well as many poikilothermic vertebrates, the male to female ratio often is 1:1. In these instances it is easy to define a deviation from normal in terms of either a relatively greater number of males or females.
  • When considering organisms with environmental sex determination (ESD), such as many reptiles and some amphibians and fish, deviations from a 1:1 relationship can and do occur that nonetheless may be normal in the context of the organism’s life history. For example, some reptile species have temperature-dependent sex determination where differentiation of developing organisms to males versus females predominates at different temperatures (Norris and Carr 2020).
  • Further complicating a generalized definition of normal sex ratios are situations where sexual differentiation is determined by a combination of genetic and environmental variables, such is the case in many fish species.

Even in species potentially requiring fewer males than females to maintain a viable population, at some point a female-biased population could become problematic in terms of having an adequate number of males to fertilize eggs produced by females or, in the longer term, ensure a robust level of genetic diversity in a population. Further, in situations where a population is male-biased relative to conditions considered normal for a given species, overall productivity may be negatively impacted due to fewer females being available to produce eggs.

A variety of external factors can produce populations that would be characterized as abnormally male-biased based on analysis of phenotypic sex ratios (examples, not comprehensive):

  • Differential mortality can occur in males versus females. This might include situations where predation or harvest techniques geared toward larger individuals, which could be either males or females depending upon species may effectively skew the apparent male to female ratio higher.
  • Endocrine disruption during early development, most prominently, during gonadal differentiation. For example, in some fish species, exposure during gonadal differentiation to androgen receptor agonists or inhibitors of cytochrome P450 19a1 (aromatase), an enzyme involved in the synthesis of 17β-estradiol, can caused male-biased populations (Delbes et al. 2022).  

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

Fundamentally, determination of sex ratio (and consequently male-biased sex ratio) is based on counts of the number of males and/or non males in a population, or some statistically representative sub-sample of a population.

  • For mature animals that are sexually dimorphic, direct observation of phenotypic secondary sex characteristics is a common method for assessing sex ratios.
  • In animals that are not sexually dimorphic or those in pubertal/juvenile stages examination of the gonad, either via gross observation or histological examination is required to determine phenotypic sex.
  • There can be instances where gonads cannot be clearly identified histologically as either testis or ovary because cell types indicative of both are simultaneously present. This type of intersex condition has been observed in some amphibians and fish, and may require a third classification category (Abdul-moneim et al. 2015).
  • For animals with GSD, genotyping or the use of genetic markers can also be employed to determine genotypic sex ratio.  However, it is noted that there are cases where genotypic sex ratio and phenotypic sex ratio may not be equivalent.

Considerations when evaluating measurements of sex ratio:

  • Care needs to be taken to collect an adequate number of animals to ensure that statistical power of the sex ratio point estimates is sufficient to address whether true deviations from normal conditions exist. It is not uncommon for published papers to report skewed sex ratios based on sample sizes far too small to result in environmentally meaningful conclusions.
  • Determination of sex ratios is generally straight-forward in a laboratory environment where all (or a defined proportion of) animals from a particular experimental treatment of interest can be collected and examined. Under such conditions, determination of a male bias relative to normal is a simple matter of a statistical comparison between the treated and control groups.
  • Determination of sex ratios in the field/wild can often be quite challenging as variables such as sampling gear used, or time and location of collection could bias samples toward one sex versus another. Additionally, often more difficult than ascertaining phenotypic male to female ratio is determining whether observations deviate from what would be considered normal for a particular species of interest. As discussed above (Key Event Description), the relative number of males normally expected will be taxa-dependent, and in some cases may also vary by region and/or environmental conditions. In cases where a male bias is being proposed for a population in the field, compelling scientific support for the “normal” sex ratio expected in the field and for the unbiased nature of the sampling should be made.

Domain of Applicability

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

Any sexually reproducing organism can theoretically experience a male-biased population, although the phenomenon certainly has not been demonstrated empirically in all species of potential concern.


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

Abul-moneim, A, DP Coulter, CT Mahapatra and MS Sepulveda. 2015. Intersex in fishes and amphibians: Population implications, prevalance, mechanisms and molecular biomarkers. J Appl Toxicol 35:1228-1240.

Delbes, G, M Blázquez, JI Fernandino, P Grigorova, BF Hales, C Metcalfe, L. Navarro-Martín, L Parent, B Robairee, A Rwigemera, G Van Der Kraak, M Wade and V Marlatt. 2022. Effects of endocrine-disrupting chemicals on gonad development: Mechanistic insights from fish and mammals. Environ Res 204B,

Norris, DO and JA. Carr. 2020. Vertebrate Endocrinology, 6th Edition. Elsevier.