Activation of NF-kappaB prevents the transition from juvenile ovary to testis and promotes ovarian development in zebrafish

Pradhan, A., Khalaf, H., Ochsner, S.A., Sreenivasan, R., Koskinen, J., Karlsson, M., Karlsson, J., McKenna, N.J., Orban, L., and Olsson, P.E.
The Journal of biological chemistry   287(45): 37926-37938 (Journal)
Registered Authors
Orban, Laszlo, Pradhan, Ajay, Sreenivasan, Rajini
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*
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.

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Human Disease / Model Data
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Errata and Notes