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Reduction, Plasma vitellogenin concentrations leads to Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)||adjacent||Moderate||Low||Evgeniia Kazymova (send email)||Open for citation & comment||TFHA/WNT Endorsed|
|Aromatase inhibition leading to reproductive dysfunction||adjacent||Moderate||Low||Cataia Ives (send email)||Open for citation & comment||TFHA/WNT Endorsed|
|Estrogen receptor antagonism leading to reproductive dysfunction||adjacent||Moderate||Low||Evgeniia Kazymova (send email)||Open for citation & comment||EAGMST Under Review|
|Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation||adjacent||Moderate||Allie Always (send email)||Under Development: Contributions and Comments Welcome|
|Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription||adjacent||Evgeniia Kazymova (send email)||Under Development: Contributions and Comments Welcome|
|Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR||adjacent||Moderate||Low||Arthur Author (send email)||Under development: Not open for comment. Do not cite|
Life Stage Applicability
|Adult, reproductively mature||High|
Key Event Relationship Description
SEE BIOLOGICAL PLAUSIBILITY BELOW
Evidence Supporting this KER
Vitellogenin synthesized in the liver and transported to the ovary via the circulation is the primary source of egg yolk proteins in fish (Wallace and Selman 1981; Tyler and Sumpter 1996; Arukwe and Goksøyr 2003). In many teleosts vitellogenesis can account for up to 95% of total egg size (Tyler and Sumpter 1996).
Uncertainties and Inconsistencies
Not all fish reproduction studies showing reductions in plasma vitellogenin have caused visible decreases in yolk protein content in oocytes and overall reductions in ovarian stage. (Ankley et al. 2005; Sun et al. 2007; Skolness et al. 2013).
While plasma vitellogenin is well established as the only major source of vitellogenins to the oocyte, the extent to which a decrease will impact an ovary that has already developed vitellogenic staged oocytes is less certain. It would be assumed that the more rapid the turn-over of oocytes in the ovary, the tighter the linkage between these KEs. Thus, repeat spawning species with asynchronous oocyte development that spawn frequently would likely be more vulnerable than annual spawning species with synchronous oocyte development that had already reached late vitellogenic stages.
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
This KER is expected to be primarily applicable to oviparous vertebrates that synthesize vitellogenin in hepatic tissue which is ultimately incorporated into oocytes present in the ovary.
- Ankley GT, Jensen KM, Durhan EJ, Makynen EA, Butterworth BC, Kahl MD, et al. 2005. Effects of two fungicides with multiple modes of action on reproductive endocrine function in the fathead minnow (Pimephales promelas). Toxicol Sci 86(2): 300-308.
- Ankley GT, Jensen KM, Makynen EA, Kahl MD, Korte JJ, Hornung MW, et al. 2003. Effects of the androgenic growth promoter 17-b-trenbolone on fecundity and reproductive endocrinology of the fathead minnow. Environmental Toxicology and Chemistry 22(6): 1350-1360.
- Ankley GT, Kahl MD, Jensen KM, Hornung MW, Korte JJ, Makynen EA, et al. 2002. Evaluation of the aromatase inhibitor fadrozole in a short-term reproduction assay with the fathead minnow (Pimephales promelas). Toxicological Sciences 67: 121-130.
- Arukwe A, Goksøyr A. 2003. Eggshell and egg yolk proteins in fish: hepatic proteins for the next generation: oogenetic, population, and evolutionary implications of endocrine disruption. Comparative Hepatology 2(4): 1-21.
- 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.
- Skolness SY, Blanksma CA, Cavallin JE, Churchill JJ, Durhan EJ, Jensen KM, et al. 2013. Propiconazole Inhibits Steroidogenesis and Reproduction in the Fathead Minnow (Pimephales promelas). Toxicological sciences : an official journal of the Society of Toxicology 132(2): 284-297.
- Sun L, Zha J, Spear PA, Wang Z. 2007. Toxicity of the aromatase inhibitor letrozole to Japanese medaka (Oryzias latipes) eggs, larvae and breeding adults. Comp Biochem Physiol C Toxicol Pharmacol 145(4): 533-541.
- Tyler C, Sumpter J. 1996. Oocyte growth and development in teleosts. Reviews in Fish Biology and Fisheries 6: 287-318.
- Wallace RA, Selman K. 1981. Cellular and dynamic aspects of oocyte growth in teleosts. American Zoologist 21: 325-343.