Positive actions of fibroblast growth factor 21 on female zebrafish reproductive axis

Fibroblast growth factor 21 (Fgf21) is a member of the endocrine subfamily of fibroblast growth factors. In mammals, FGF21 regulates glucose and lipid metabolism, and energy balance. Fgf21 was recently demonstrated to stimulate feed intake and regulate energy balance in zebrafish. The physiological mechanisms that regulate energy balance are tightly interlinked with reproduction. As a first step to extend our original findings on Fgf21 and energy balance, this research aimed to determine whether Fgf21 regulates the reproductive axis in zebrafish. Using quantitative PCR, we demonstrate the expression of fgf21, its receptor fgfr1c, and co-receptor β-klotho; and FGF21-like immunoreactivity (immunohistochemistry) in the zebrafish ovary and liver cells. These results suggest local production of FGF21 and possible actions within the ovary. Single intraperitoneal (IP) injection of 1, 10, or 100 ng/g bodyweight FGF21 significantly (ANOVA, P < 0.05) upregulated reproductive hormone genes in the brain; gonadotropin-releasing hormone isoforms (sgnrh/cgnrh-III) and kisspeptin (kiss1), and gonads; aromatase (cyp19a1a) and gonadotropin receptors (fshr, lhr) that are critical for reproductive success. FGF21 significantly (ANOVA, P < 0.05) upregulated vitellogenin transcript levels and total vitellogenin concentration (ELISA) in zebrafish liver cells at 1 h and 24 h post-incubation, respectively. Lastly, at 100 ng/mL, FGF21 induced (ANOVA P < 0.05) oocyte maturation in vitro (determined by germinal vesicle breakdown quantification). These results support a very strong positive role for Fgf21 in the reproductive endocrine axis of zebrafish.