Knockout of Gnrh2 in zebrafish (Danio rerio) reveals its roles in regulating feeding behavior and oocyte quality

Abstract

Many studies on Gnrh1, and the teleost Gnrh3, have elucidated the roles of these peptides in reproductive regulation. However, the role of the midbrain population of Gnrh, Gnrh2, has long been a mystery, despite its ubiquitous conservation in all jawed vertebrates except rodents. Previous behavioral studies in sparrows, musk shrews, mice, zebrafish, and goldfish show that Gnrh2 administrations both increase spawning behaviors and decrease feeding behaviors, suggesting a role of this peptide in metabolism regulation along with the canonical role in regulating reproduction. In order to more deeply explore the roles of Gnrh2, we used a cyprinid teleost, zebrafish, which has 2 forms of Gnrh, Gnrh2 and Gnrh3, to generate a knockout zebrafish line which contains a frameshift mutation and subsequent disruption of the coding for the functional Gnrh2 peptide. We examined differences in reproduction, feeding, growth, and mobility in this line, and discovered major differences in feeding and growth parameters, suggesting that Gnrh2 is a potent anorexigen in zebrafish. Additionally, there were no differences in mobility except for increased distances swam during feeding periods. There were no major differences in reproductive success, however, female gnrh2−/− zebrafish exhibited smaller oocytes and increased embryo mortality, indicating slightly decreased oocyte quality. Additionally, there were changes in the expression levels of many feeding, growth, and reproductive neuropeptides in gnrh2−/− zebrafish. Taken together, these findings suggest a role for Gnrh2 in controlling satiation in zebrafish along with a minor role in maintaining optimal oocyte quality in females.