- 1 Key Event Relationship Overview
- 2 How Does This Key Event Relationship Work
- 3 Weight of Evidence
- 4 Quantitative Understanding of the Linkage
- 5 Evidence Supporting Taxonomic Applicability
- 6 References
Key Event Relationship Overview
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Description of Relationship
|Upstream Event||Downstream Event/Outcome|
|Vitellogenin accumulation into oocytes and oocyte growth/development, Reduction||Cumulative fecundity and spawning, Reduction|
AOPs Referencing Relationship
|AOP Name||Type of Relationship||Weight of Evidence||Quantitative Understanding|
|Aromatase inhibition leading to reproductive dysfunction||Directly Leads to||Moderate||Moderate|
|Androgen receptor agonism leading to reproductive dysfunction||Directly Leads to||Moderate||Moderate|
|Estrogen receptor antagonism leading to reproductive dysfunction||Directly Leads to||Moderate||Moderate|
|Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation||Directly Leads to|
|Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription||Directly Leads to|
How Does This Key Event Relationship Work
SEE BIOLOGICAL PLAUSIBILITY BELOW
Weight of Evidence
Vitellogenesis is a critical stage of oocyte development and accumulated lipids and yolk proteins make up the majority of oocyte biomass (Tyler and Sumpter 1996). At least in mammals, maintenance of meiotic arrest is supported by signals transmitted through gap junctions between the granulosa cells and oocytes (Jamnongjit and Hammes 2005). Disruption of oocyte-granulosa contacts as a result of cell growth has been shown to coincide with oocyte maturation (Eppig 1994). However, it remains unclear whether the relationship between vitellogenin accumulation and oocyte growth and eventual maturation is causal or simply correlative.
Empirical Support for Linkage
At present, to our best knowledge there are no studies that definitively demonstrate a direct cause-effect relationship between impaired VTG accumulation into oocytes and impaired spawning. There is, however, strong correlative evidence. Across a range of laboratory studies with small fish, there is a robust and statistically significant correlation between reductions in circulating VTG concentrations and reductions in cumulative fecundity (Miller et al. 2007). To date, we are unaware of any fish reproduction studies which show a large reduction in circulating VTG concentrations, but not reductions in cumulative fecundity.
Uncertainties or Inconsistencies
Based on the limited number of studies available that have examined both of these KEs, there are no known, unexplained, results that are inconsistent with this relationship.
Quantitative Understanding of the Linkage
Across a range of laboratory studies with fathead minnow, there is a robust and statistically significant correlation between reductions in circulating VTG concentrations and reductions in cumulative fecundity (Miller et al. 2007). At present it is unclear how well that relationship may hold for other fish species or feral fish under the influence of environmental variables. A model based on a statistical relationship between plasma E2 concentrations, spawning interval, and cumulative fecundity has been developed to predict changes in cumulative fecundity from plasma VTG (Li et al. 2011b). However, to date, such models do not specifically consider vitellogenin uptake into oocytes as a quantitative predictor of fecundity. Furthermore, with the exception of a few specialized studies, quantitative measures of VTG content in oocytes are rarely measured in toxicity studies. In contrast, plasma VTG is routinely measured.
Evidence Supporting Taxonomic Applicability
On the basis of the taxonomic relevance of the two KEs linked via this KER, this KER is likely applicable to aquatic, oviparous, vertebrates which both produce vitellogenin and deposit eggs/sperm into an aquatic environment.
- Tyler C, Sumpter J. 1996. Oocyte growth and development in teleosts. Reviews in Fish Biology and Fisheries 6: 287-318.
- Jamnongjit M, Hammes SR. 2005. Oocyte maturation: the coming of age of a germ cell. Seminars in reproductive medicine 23(3): 234-241.
- Eppig JJ. 1994. Further reflections on culture systems for the growth of oocytes in vitro. Human reproduction 9(6): 974-976.
- Miller DH, Jensen KM, Villeneuve DL, Kahl MD, Makynen EA, Durhan EJ, et al. 2007. Linkage of biochemical responses to population-level effects: a case study with vitellogenin in the fathead minnow (Pimephales promelas). Environ Toxicol Chem 26(3): 521-527.
- Li Z, Villeneuve DL, Jensen KM, Ankley GT, Watanabe KH. 2011b. A computational model for asynchronous oocyte growth dynamics in a batch-spawning fish. Can J Fish Aquat Sci 68: 1528-1538.