Pradhan, A., Khalaf, H., Ochsner, S.A., Sreenivasan, R., Koskinen, J., Karlsson, M., Karlsson, J., McKenna, N.J., Orban, L., and Olsson, P.E. (2012) Activation of NF-kappaB prevents the transition from juvenile ovary to testis and promotes ovarian development in zebrafish. The Journal of biological chemistry. 287(45):37926-37938.
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.