Control of testes mass by androgen receptor paralogs in a cichlid

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 (ARs)--which bind circulating androgens--in this regulatory pathway is unclear. Teleost fishes further complicate this question by having two paralogs of AR (AR and AR{beta}) resulting from a duplication of their ancestral genome. We investigated the functional role of these two ARs on testes growth and development by experimentally 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 receptor alleles were more likely to be male compared to fish with one or fewer, suggesting that the two paralogs of the receptor may be redundant in regulating early sex determination. In contrast, we found that adult testes size was significantly affected by distinct combinations of mutant and wild-type AR alleles. We present a working model whereby AR{beta} facilitates testes growth and AR causes testes regression. This mechanism may contribute to the robust social and physiological plasticity displayed by A. burtoni and other social teleost fish.