Activation of NF-kappaB prevents the transition from juvenile ovary to testis and promotes ovarian development in zebrafish
- Authors
- Pradhan, A., Khalaf, H., Ochsner, S.A., Sreenivasan, R., Koskinen, J., Karlsson, M., Karlsson, J., McKenna, N.J., Orban, L., and Olsson, P.E.
- ID
- ZDB-PUB-121004-1
- Date
- 2012
- Source
- The Journal of biological chemistry 287(45): 37926-37938 (Journal)
- Registered Authors
- Orban, Laszlo, Pradhan, Ajay, Sreenivasan, Rajini
- Keywords
- apoptosis, development, inflammation, signal transduction, zebrafish, gonad, gonad transformation, sex determination, sex differentiation, sex reversal
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Apoptosis/genetics
- Blotting, Western
- Cell Line
- Deoxycholic Acid/pharmacology
- Escherichia coli/immunology
- Female
- Gene Expression Profiling
- Gene Regulatory Networks
- Hot Temperature
- Male
- Models, Genetic
- NF-kappa B/antagonists & inhibitors
- NF-kappa B/genetics
- NF-kappa B/metabolism*
- Oligonucleotide Array Sequence Analysis
- Ovary/growth & development*
- Ovary/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Sex Differentiation/drug effects
- Sex Differentiation/genetics
- Signal Transduction/drug effects
- Signal Transduction/genetics
- Testis/growth & development*
- Testis/metabolism
- Transcriptome/genetics
- Transcriptome/immunology
- Zebrafish/genetics
- Zebrafish/immunology
- Zebrafish/metabolism*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 22988238 Full text @ J. Biol. Chem.
Testis differentiation in zebrafish involves juvenile ovary to testis transformation initiated by an apoptotic wave. The molecular regulation of this transformation process is not fully understood. NF-κB is activated at an early stage of development and has been shown to interact with steroidogenic factor-1 (Sf-1) in mammals, leading to the suppression of anti-Mullerian hormone (Amh) gene expression. Since Sf-1 and Amh are important for proper testis development, NF-κB-mediated induction of anti-apoptotic genes could therefore also play a role in zebrafish gonad differentiation. The aim of the present study was to examine the potential role of NF-κB in zebrafish gonad differentiation. Exposure of juvenile zebrafish to heat-killed E. coli activated the NF-κB pathways and resulted in an increased ratio of females. Microarray and qRT-PCR analysis of gonads showed elevated expression of NF-κB-regulated genes. To confirm the involvement of NF-κB-induced anti-apoptotic effects, zebrafish were treated with sodium deoxycholate (DOC) a known inducer of NF-κB or NF-κB activation inhibitor (NAI). DOC treatment mimicked the effect of heat-killed bacteria and resulted in increased proportion of females, while the inhibition of NF-κB using NAI resulted in more males. This study provides proof for an essential role of NF-κB in gonadal differentiation of zebrafish and represents an important step towards the complete understanding of the complicated process of sex differentiation in zebrafish and possibly other cyprinid teleosts as well.