title: In situ forming microparticle implants for delivery of sex steroids in fish: Modulation of the immune response of gilthead seabream by testosterone.
abstract: Current knowledge on the sensitivity of marine fish to androgenic environmental chemicals is limited, despite the growing interest in the effects of endocrine disrupting chemicals. To study in vivo the effects of testosterone (T) on the fish immune response, we used a microencapsulation implant technique, the in situ forming microparticle system, containing 1 mg T/kg body weight (T-ISM), in adult specimens of gilthead seabream (Sparus aurata L.), a species of great economic interest. We demonstrated that implants themselves (without T) have no significant effect on most of the parameters measured. In T-ISM implanted fish, T serum levels reached supraphysiological concentrations accompanied by a slight increase in 11-ketotestosterone and 17β-estradiol levels 21 days post-implantation (dpi). Liver and head-kidney samples were processed 7 and 21 dpi to assess T-ISM effect on (i) the mRNA expression of genes involved in the metabolism of steroid hormones and in the immune response, and (ii) phagocyte activities. The expression profile of cytokines, chemokines and immune receptors was altered in T-ISM implanted animals that showed an early pro-inflammatory tendency, and then, a mixed pro-/anti-inflammatory activation during longer exposure. Furthermore, the enhancement of phagocytic activity and the production of reactive oxygen species by leukocytes 21 dpi in T-ISM implanted specimens suggest fine modulation of the innate immune response by T. Taken together, these data demonstrate for the first time the feasibility of using ISM implants in an aquatic species, and provide new data on the role played by T on the immune response in fish.
authors.affiliation: Department of Cell Biology and Histology, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, 30100 Murcia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Castillo-Briceño
authors.forename: S
authors.initials: S
authors.lastname: Aguila-Martínez
authors.forename: S
authors.initials: S
authors.lastname: Liarte
authors.forename: A
authors.initials: A
authors.lastname: García Alcázar
authors.forename: J
authors.initials: J
authors.lastname: Meseguer
authors.forename: V
authors.initials: V
authors.lastname: Mulero
authors.forename: A
authors.initials: A
authors.lastname: García-Ayala
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000276:immunology; D016503:Drug Delivery Systems; D004343:Drug Implants; D005393:Fish Diseases / Q000276:immunology / Q000382:microbiology; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D005398:Fisheries; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D060226:Head Kidney / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D056747:Immunomodulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D010587:Phagocytosis; D021541:Sea Bream / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction; D013739:Testosterone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014733:Vibrio / Q000276:immunology
chemical_list: D004269:DNA, Bacterial; D004343:Drug Implants; D029941:Fish Proteins; D007155:Immunologic Factors; D013739:Testosterone; D019363:Cytochrome P-450 CYP1A1