Abstract
Steroid hormones play numerous important and diverse roles in the differentiation and development of vertebrate primary and secondary reproductive characteristics. However, the exact role of androgen receptors—which bind circulating androgens—in this regulatory pathway is unclear. Teleost fishes further complicate this question by having two paralogs of the androgen receptor (ARα and ARβ) resulting from a duplication of their ancestral genome. We investigated the functional role of these two ARs on adult testes mass, by eliminating receptor function of one or both paralogs using CRISPR/Cas9 genome edited Astatotilapia burtoni, an African cichlid fish. Fish with two or more functional AR alleles were more likely to be male compared to fish with one or fewer, suggesting that the two paralogs may play redundant roles in the A. burtoni sex determination system. We replicated previous work showing that fish lacking functional ARβ possess testes smaller than wild-type fish, while fish lacking ARα possess testes larger than wild-type fish. However, we found novel evidence supporting a complex relationship between the two AR paralogs in the regulation of testes mass. For instance, the effects of ARα mutation on testes mass are eliminated in homozygous ARβ mutants but the reverse is not true. These results suggest a dynamic relationship between these two AR paralogs where ARβ functions may be permissive to ARα functions in the control of testes mass. This mechanism may contribute to the robust physiological plasticity displayed by A. burtoni and other social teleost fishes.
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Acknowledgements
We thank Vibhav Laud (Stanford University) for assistance dissecting fish. We also thank Humayd Mirza and Rohail Siddiqi (University of Houston) for assistance with PCRs and genotyping. Lastly, we thank Mariana Lopez and Lillian Jackson (University of Houston) for providing feedback on an earlier version of this manuscript.
Funding
This work was supported by an Arnold O. Beckman Fellowship to B.A.A., a University of Houston–National Research University Fund grant R0503962 to B.A.A., and NIH grants NS034950, MH101373, and MH096220 to R.D.F.
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Conceptualization—BAA, APH, RDF; methodology—BAA, APH; investigation—BAA, APH; writing—original draft, APH; writing—review and editing, BAA, APH; supervision—BAA.
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Data and code used are available at https://github.com/AlwardLab.
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Hoadley, A.P., Fernald, R.D. & Alward, B.A. Control of testes mass by androgen receptor paralogs in a cichlid. J Comp Physiol B 192, 107–114 (2022). https://doi.org/10.1007/s00360-021-01417-2
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DOI: https://doi.org/10.1007/s00360-021-01417-2