Androgen induced cellular proliferation, neurogenesis, and generation of GnRH3 neurons in the brain of mature female Mozambique tilapia

Yasuto Narita, Atsuhiro Tsutiya, Yui Nakano, Moe Ashitomi, Kenjiro Sato, Kohei Hosono, Toyoji Kaneko, Ruo-Dong Chen, Jay-Ron Lee, Yung-Che Tseng, Pung-Pung Hwang, Ritsuko Ohtani-Kaneko
2018 Scientific Reports  
The neuroplastic mechanisms in the fish brain that underlie sex reversal remain unknown. Gonadotropin-releasing hormone 3 (GnRH3) neurons control male reproductive behaviours in Mozambique tilapia and show sexual dimorphism, with males having a greater number of GnRH3 neurons. Treatment with androgens such as 11-ketotestosterone (KT), but not 17β-estradiol, increases the number of GnRH3 neurons in mature females to a level similar to that observed in mature males. Compared with oestrogen, the
more » ... th oestrogen, the effect of androgen on neurogenesis remains less clear. The present study examined the effects of 11-KT, a non-aromatizable androgen, on cellular proliferation, neurogenesis, generation of GnRH3 neurons and expression of cell cycle-related genes in mature females. The number of proliferating cell nuclear antigen-positive cells was increased by 11-KT. Simultaneous injection of bromodeoxyuridine and 11-KT significantly increased the number of newly-generated (newlyproliferated) neurons, but did not affect radial glial cells, and also resulted in newly-generated GnRH3 neurons. Transcriptome analysis showed that 11-KT modulates the expression of genes related to the cell cycle process. These findings suggest that tilapia could serve as a good animal model to elucidate the effects of androgen on adult neurogenesis and the mechanisms for sex reversal in the fish brain. Sex reversal is a well-known phenomenon in fishes, with some naturally changing their phenotype during their lifetime and others switching sexes in response to environmental factors or hormone treatment. Fish which have undergone sex reversal have both gonads, but the reproductive behaviour of the sex they have reversed to 1 . Kobayashi et al. have reported that hormonal treatments induce heterotypical sexual behaviours in goldfish and carp 2 ; however, they also retain and exhibit sexual behaviours of their original sex in response to key stimulus 3 . These findings indicate that fish tend to have some plasticity in their neural circuits. Nile and Mozambique tilapias, commercially important fish species in aquaculture, are often subjected to artificial sex reversal during their early life stages because male fish grow faster than females. As such, androgen administration has been adopted for generating monosex (all male) tilapia 4,5 . Thorough investigation of the mechanisms underlying gonadal sex differentiation and reversal in tilapias have revealed that these processes are driven by the suppression of genes responsible for the production of one sex hormone and the activation of genes responsible for the production of the opposite sex hormone in the gonads 6-9 . However, it remains unclear how sex reversal takes place in the brain, though transcriptome analysis was recently applied to elucidate the mechanisms for the sex reversal in the brain 10,11 . The difficulty in elucidating this issue is partly because the specific neurons critically related to reproductive behaviours are not identified in sex reversal fish. Published: xx xx xxxx OPEN www.nature.com/scientificreports/
doi:10.1038/s41598-018-35303-9 fatcat:rc2jxt7amjaedccimeyp4iwkpa