Loss of Growth Hormone Gene (gh1) in Zebrafish Arrests Folliculogenesis in Females and Delays Spermatogenesis in Males

As a master hormone controlling growth and metabolism, GH is also known to regulate reproduction. Studies in mammals have shown that mutations in GH or its receptor (GHR) not only result in retardation in body growth but also reproductive dysfunctions in both sexes. However, the roles of GH in reproduction of other vertebrates are poorly defined. In this study, we created two zebrafish GH (gh1) mutant lines using CRISPR/Cas9. The mutant developed normally up to 14 days postfertilization (dpf); however, a high rate of mortality was observed afterward in both lines, and only a small number of mutant fish could survive to adult stage. The body growth of the mutants was significantly retarded in both sexes in a gene dose-dependent manner compared with their wild-type siblings. A severe dysfunction of gonadal development was observed in survived mutant females, with ovarian folliculogenesis being arrested completely at primary growth stage until 100 dpf. Interestingly, the folliculogenesis in the mutant resumed after months of delay with a certain number of follicles entering vitellogenic growth. As for male reproduction, although the spermatogenesis in mutant males seemed normal in adults, the GH-insufficient heterozygote showed an...Continue Reading