Sex-specific immunomodulatory action of the environmental estrogen 17α-ethynylestradiol alongside with reproductive impairment in fish

• Published in: Aquatic toxicology 2018-10, Vol.203, p.95-106
• Main Authors: Ye, Roy R., Peterson, Drew R., Kitamura, Shin-Ichi, Segner, Helmut, Seemann, Frauke, Au, Doris W.T.
• Format: Article
• Language: English
• Subjects: Complement system; E. tarda; EE2; Estrogenic EDCs; Immunotoxicity; Innate immunity; Marine medaka; Oryzias melastigma; Reproductive impairment; Sex-difference; Toll-like receptor
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2018.07.019

•EE2 exposure of adult O. melastigma revealed distinct sex differences in the EE2-mediated biological responses.•Females: immune enhancement and restored reproduction at low, persistent reproductive impairment at high EE2 concentrations.•Males: direct EE2 exposure impaired reproduction and immune competence dose-dependent with recovery upon EE2 abatement.•Downregulation of hepatic tlr3 and c3 (in female) and tlr3, tlr5 and c3 (in male) may be indicative of impaired fish immune competence.•Adult EE2 exposure may affect F0 population survival through reduced immune competence and F1 output through impaired reproduction. Estrogenic endocrine disrupting chemicals (EEDCs) are present ubiquitously in sediments and aquatic ecosystems worldwide. The detrimental impact of EEDCs on the reproduction of wildlife is widely recognized. Increasing evidence shows the immunosuppressive effects of EEDCs in vertebrates. Yet, no studies have considered concomitantly EEDC-induced impacts on reproductive impairment and immune suppression in vivo, which are deemed essential for risk assessment and environmental monitoring. In this study, EE2 was used as a representative EEDC, for parallel evaluation of EEDC-induced immune suppression (immune marker gene expression, leukocyte numbers, host resistance assay, and immune competence index) and reproductive impairment (estrogen responsive gene expression, fecundity, fertilization success, hatching success, and reproductive competence index) in an established fish model (marine medaka Oryzias melastigma), considering sex-specific induction and adaptation and recovery responses under different EE2 exposure scenarios. The findings in marine medaka reveal distinct sex differences in the EE2-mediated biological responses. For female fish, low concentration of exogenous EE2 (33 ng/L) could induce hormesis (immune enhancement), enable adaptation (restored reproduction) and even boost fish resistance to bacterial challenge after abatement of EE2. However, a prolonged exposure to high levels of EE2 (113 ng/L) not only impaired F0 immune function, but also perturbed females recovering from reproductive impairment, resulting in a persistent impact on the F1 generation output. Thus, for female fish, the exposure concentration of EE2 is more critical than the dose of EE2 in determining the impacts of EE2 on immune function and reproduction. Conversely, male fish are far more sensitive than females to the presence of low levels of exogenous EE2 in