title: Activation of NF-κB protein prevents the transition from juvenile ovary to testis and promotes ovarian development in zebrafish.
abstract: 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 in mammals, leading to the suppression of anti-Müllerian hormone (Amh) gene expression. Because steroidogenic factor-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 this study was to examine the potential role of NF-κB in zebrafish gonad differentiation. Exposure of juvenile zebrafish to heat-killed Escherichia coli activated the NF-κB pathways and resulted in an increased ratio of females from 30 to 85%. Microarray and quantitative real-time-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, a known inducer of NF-κB or NF-κB activation inhibitor (NAI). Sodium deoxycholate treatment mimicked the effect of heat-killed bacteria and resulted in an increased proportion of females from 25 to 45%, whereas the inhibition of NF-κB using NAI resulted in a decrease in females from 45 to 20%. This study provides proof for an essential role of NF-κB in gonadal differentiation of zebrafish and represents an important step toward the complete understanding of the complicated process of sex differentiation in this species and possibly other cyprinid teleosts as well.
authors.affiliation: Department of Biology, Örebro Life Science Center, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
authors.forename: Ajay
authors.initials: A
authors.lastname: Pradhan
authors.forename: Hazem
authors.initials: H
authors.lastname: Khalaf
authors.forename: Scott A
authors.initials: SA
authors.lastname: Ochsner
authors.forename: Rajini
authors.initials: R
authors.lastname: Sreenivasan
authors.forename: Jarno
authors.initials: J
authors.lastname: Koskinen
authors.forename: Marie
authors.initials: M
authors.lastname: Karlsson
authors.forename: Jesper
authors.initials: J
authors.lastname: Karlsson
authors.forename: Neil J
authors.initials: NJ
authors.lastname: McKenna
authors.forename: László
authors.initials: L
authors.lastname: Orbán
authors.forename: Per-Erik
authors.initials: PE
authors.lastname: Olsson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D003840:Deoxycholic Acid / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006358:Hot Temperature; D008297:Male; D008957:Models, Genetic; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012733:Sex Differentiation / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013737:Testis / Q000254:growth & development* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D015027:Zebrafish / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D029961:Zebrafish Proteins; D003840:Deoxycholic Acid