PUBLICATION
Targeted mutation of secretogranin-2 disrupts sexual behavior and reproduction in zebrafish
- Authors
- Mitchell, K., Zhang, W.S., Lu, C., Tao, B., Chen, L., Hu, W., Trudeau, V.L.
- ID
- ZDB-PUB-200530-4
- Date
- 2020
- Source
- Proceedings of the National Academy of Sciences of the United States of America 117(23): 12772-12783 (Journal)
- Registered Authors
- Trudeau, V.L.
- Keywords
- behavior, ovulation, reproduction, secretogranin-2, secretoneurin
- MeSH Terms
-
- Animals
- Female
- Fertility*
- Gonadotropin-Releasing Hormone/metabolism
- Hypothalamus/metabolism
- Luteinizing Hormone/metabolism
- Male
- Mating Preference, Animal*
- Mutation*
- Neuropeptides/metabolism
- Oviposition
- Ovulation
- Pituitary Gland/metabolism
- Secretogranin II/genetics*
- Secretogranin II/metabolism
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 32467166 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Mitchell, K., Zhang, W.S., Lu, C., Tao, B., Chen, L., Hu, W., Trudeau, V.L. (2020) Targeted mutation of secretogranin-2 disrupts sexual behavior and reproduction in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 117(23):12772-12783.
Abstract
The luteinizing hormone surge is essential for fertility as it triggers ovulation in females and sperm release in males. We previously reported that secretoneurin-a, a neuropeptide derived from the processing of secretogranin-2a (Scg2a), stimulates luteinizing hormone release, suggesting a role in reproduction. Here we provide evidence that mutation of the scg2a and scg2b genes using TALENs in zebrafish reduces sexual behavior, ovulation, oviposition, and fertility. Large-scale spawning within-line crossings (n = 82 to 101) were conducted. Wild-type (WT) males paired with WT females successfully spawned in 62% of the breeding trials. Spawning success was reduced to 37% (P = 0.006), 44% (P = 0.0169), and 6% (P < 0.0001) for scg2a-/- , scg2b-/- , and scg2a-/-;scg2b-/- mutants, respectively. Comprehensive video analysis indicates that scg2a-/-;scg2b-/- mutation reduces all male courtship behaviors. Spawning success was 47% in saline-injected WT controls compared to 11% in saline-injected scg2a-/-;scg2b-/- double mutants. For these mutants, spawning success increased 3-fold following a single intraperitoneal (i.p.) injection of synthetic secretoneurin-a (P = 0.0403) and increased 3.5-fold with injection of human chorionic gonadotropin (hCG). Embryonic survival at 24 h remained on average lower in scg2a-/-;scg2b-/- fish compared to WT injected with secretoneurin-a (P < 0.001). Significant reductions in the expression of gonadotropin-releasing hormone 3 in the hypothalamus, and luteinizing hormone beta and glycoprotein alpha subunits in the pituitary provide evidence for disrupted hypothalamo-pituitary function in scg2a and scg2b mutant fish. Our results indicate that secretogranin-2 is required for optimal reproductive function and support the hypothesis that secretoneurin is a reproductive hormone.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping