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Relationship: 2146
Title
Increased, Differentiation to Testis leads to Increased, Male Biased Sex Ratio
Upstream event
Downstream event
AOPs Referencing Relationship
| AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|---|---|
| Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation | adjacent | High | Brendan Ferreri-Hanberry (send email) | Under Development: Contributions and Comments Welcome | EAGMST Under Review | |
| Androgen receptor agonism leading to male-biased sex ratio | adjacent | Evgeniia Kazymova (send email) | Open for citation & comment | EAGMST Under Review |
Taxonomic Applicability
Sex Applicability
| Sex | Evidence |
|---|---|
| Male | Moderate |
Life Stage Applicability
| Term | Evidence |
|---|---|
| Juvenile | Moderate |
| Development | Moderate |
Prior to gonadal sex determination in vertebrates, the developing organism has a primordial bipotential gonad that can be fated to either sex depending on the genetic makeup of the embryo (genetic sex determination; GSD) or environmental conditions (environmental sex determination; ESD) or a combination of both factors.
Regardless of whether gonadal development is controlled via GSD or ESD (or both), the operational definition of male versus female in terms of function usually is defined by the presence, respectively, of testes versus ovaries. For species exhibiting sex-specific secondary sexual characteristics preferential differentiation to testis can be accompanied by easily discerned external phenotypic changes as well. If there is increased differentiation to testis in individuals of a population of organisms this will by default produce a male biased sex ratio as defined by what would be considered normal for that species.
| ID | Experimental Design | Species | Upstream Observation | Downstream Observation | Citation (first author, year) | Notes |
|---|
| Title | First Author | Biological Plausibility |
Dose Concordance |
Temporal Concordance |
Incidence Concordance |
|---|
Biological Plausibility
Dose Concordance Evidence
Temporal Concordance Evidence
Incidence Concordance Evidence
Uncertainties and Inconsistencies
A major uncertainty for this KER involves what would be defined as "normal" for degree of testis differentiation and by extension sex ratio. There needs to be knowledge as to baseline expectations for testis differentiation for a given species in a given habitiat (or lab setting) to ascertain whether increases are occurring. Baseline information of this type is available or can be inferred for some species but certainly not for all that might be considered.
A second significant uncertainty involves situations where the gonad cannot be clearly defined as either testis or ovary. This can occur in some fish and amphibian species, where the gonad has cell types indicative of both testes and ovaries (Abdul-moneim et al. 2015). In these instances classification of individuals as male versus female may not be possible, requiring a third category related to an intersex condition. There are seemingly multiple underlying causes of intersex, one of which appears to be exposure to estrogenic chemicals during gonad differentiation (Jobling et al. 1998; Norris et al. 2018; Grim et al. 2020).
A third uncertainty involves whether all individuals defined as males based on gonad phenotype will have the same degree of function in terms of producing viable gametes. It is possible, for example, that genotypic females which develop a male phenotype due to an environmental factor such as exposure to an endocrine-active chemical may not be functionally equivalent to a genetic male relative to sperm production/viability. This could be an important consideration relative to the types of predictions attempted based on a male-biased sex ratio in a population.
Not applicable.
Because the degree of testis occurrence in a given population dictates the relative number of organisms defined as males, there is a direct quantitative relationship between the two KEs.
Response-response Relationship
Not applicable.
Time-scale
Timescales will vary based on species-specific developmental rates, but since one KE often will define the second (i.e., an animal is defined as a male based on the presence of testis) timescale may not be a relevant consideration.
Known Feedforward/Feedback loops influencing this KER
Not applicable.
This KER is applicable to any species in which males are defined by the occurrence of testis and/or associated male secondary sexual characteristics.