Gender-specific modulation of immune system complement gene expression in marine medaka Oryzias melastigma following dietary exposure of BDE-47

Abstract

BDE-47 is one of the most widely found congeners of PBDEs in marine environments. The potential immunomodulatory effects of BDE-47 on fish complement system were studied using the marine medaka Oryzias melastigma as a model fish. Three-month-old O. melastigma were subjected to short-term (5 days) and long-term (21 days) exposure to two concentrations of BDE-47 (low dose at 290 ± 172 ng/day; high dose at 580 ± 344 ng/day) via dietary uptake of BDE-47 encapsulated in Artemia nauplii. Body burdens of BDE-47 and other metabolic products were analyzed in the exposed and control fish. Only a small amount of debrominated product, BDE-28, was detected, while other metabolic products were all under detection limit. Transcriptional expression of six major complement system genes involved in complement activation: C1r/s (classical pathway), MBL-2 (lectin pathway), CFP (alternative pathway), F2 (coagulation pathway), C3 (the central component of complement system), and C9 (cell lysis) were quantified in the liver of marine medaka. Endogenous expression of all six complement system genes was found to be higher in males than in females (p < 0.05). Upon dietary exposure of marine medaka to BDE-47, expression of all six complement genes were downregulated in males at day 5 (or longer), whereas in females, MBl-2, CFP, and F2 mRNAs expression were upregulated, but C3 and C9 remained stable with exposure time and dose. A significant negative relationship was found between BDE-47 body burden and mRNA expression of C1r/s, CFP, and C3 in male fish (r = −0.8576 to −0.9447). The above findings on changes in complement gene expression patterns indicate the complement system may be compromised in male O. melastigma upon dietary exposure to BDE-47. Distinct gender difference in expression of six major complement system genes was evident in marine medaka under resting condition and dietary BDE-47 challenge. The immunomodulatory effects of BDE-47 on transcriptional expression of these complement components in marine medaka were likely induced by the parent compound instead of biotransformed products. Our results clearly demonstrate that future direction for fish immunotoxicology and risk assessment of immunosuppressive chemicals must include parallel evaluation for both genders.Electronic supplementary materialThe online version of this article (doi:10.1007/s11356-012-0887-z) contains supplementary material, which is available to authorized users.

20 Years of fish immunotoxicology – what we know and where we are

“…For instance, observed that exposure of rainbow trout to municipal sewage treatment effluents resulted in decreased antibody production and reduced lymphocyte number in sexually mature females but not in males. Similarly, Ye et al (2012) found sexspecific differences in the response of the complement system of the marine medaka (Oryzias melastigma) exposed to a polybrominated flame retardant. These examples show that the fact that 79% of the published immunotoxicity studies do not provide information on the sex of the experimental fish, represents a serious information gap.…”

Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

“…Moreover, the BDE-47-stimulated increased mRNA levels of IL-6 and IL-8, suggesting that activation of transcription contributes to the overall increased cytokine expression. Because the fold change in cytokine protein production was modest compared to the fold change in cytokine mRNA expression, additional post-transcriptional mechanisms may modulate protein expression (Griesinger et al , 2001; Wang et al , 2011; Ye et al , 2011). …”

Tissue-specific transcriptome assemblies of the marine medaka Oryzias melastigma and comparative analysis with the freshwater medaka Oryzias latipes

“…The marine medaka Oryzias melastigma ( O. melastigma ) is an emerging marine fish model used in the investigation of the response of organisms to pollutants, toxins and stresses in marine environments [ 5 , 6 ]. In fact, O. melastigma is already used in a variety of estuarine and marine ecotoxicological studies [ 7 - 10 ], demonstrating their potential in studying the effect of organic chemicals, inorganic chemicals, microorganism and environmental stresses in relation to cardiac toxicity [ 11 ], hepatotoxicity [ 9 ], neurotoxcity [ 12 ], immunotoxicity [ 10 ], and so forth. In addition, O. melastigma has been adopted by the International Life Sciences Institute (ILSI) Health and Environmental Science Institute (HESI) for embryo toxicity testing.…”