RNA interference-mediated silencing of retinoid X receptor causes reproductive failure in the sea lice Caligus rogercresseyi

Nuclear receptors (NRs) belong to a superfamily of phylogenetically conserved genes implicated in critical physiological functions including reproduction and development. Considering the vast array of processes controlled by NRs, modulating the NR signaling may provide exciting and novel therapeutic opportunities for treating parasitic diseases. The copepod Caligus rogercresseyi is a common fish ectoparasite that produces sig-nificant negative economic impact on the salmon aquaculture industry. The present study expands on the knowledge of NRs in parasitic copepods, examining their diversity, expression and localization in C. rogercresseyi. Furthermore, we evaluated the phenotypic consequences of the functional knock-down of the NR retinoid X re-ceptor (Cr-RXR) in C. rogercresseyi. A panel of 18 NRs transcript sequences were identified, exhibiting a distinctive regulation among egg, copepodid, chalimus and adults, as revealed using RNA-seq and RT-qPCR data. Higher relative expression was found in females compared to chalimi and male stages for retinoid X receptor (Cr-RXR), ecdysone receptor (Cr-EcR) and hormone receptor 3 (Cr-HR3). Localization of Cr-RXR and Cr-EcR transcripts was also examined using in situ hybridization, showing strong labelling in ovaries, oocytes and intestine of sea lice. Furthermore, RNAi-induced gene silencing of Cr-RXR caused delayed egg string production, severely reduced fecundity, and generated abnormal gonad and embryo development. These results suggest a physiological role for NRs in C. rogercresseyi reproductive tract development, expanding our knowledge of genes involved in reproduction and development in sea lice. Our findings may be useful for the future development of novel antiparasitic compounds to improve fish farming.