The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review

Abstract

During the last decade, a number of studies have shown that, in addition to their classically described reproductive function, estrogens and androgens also regulate the immune system in teleosts. Today, several molecules are known to interfere with the sex-steroid signaling. These chemicals are often referred to as endocrine disrupting contaminants (EDCs). We review the growing evidence that these compounds interfere with the fish immune system. These studies encompass a broad range of approaches from field studies to those at the molecular level. This integrative overview improves our understanding of the various endocrine-disrupting processes triggered by these chemicals. Furthermore, the research also explains why fish that have been exposed to EDCs are more sensitive to pathogens during gametogenesis. In this review, we first discuss the primary actions of sex-steroid-like endocrine disruptors in fish and the specificity of the fish immune system in comparison to mammals. Then, we review the known interactions between the immune system and EDCs and interpret the primary effects of sex steroids (estrogens and androgens) and their related endocrine disruptors on immune modulation. The recent literature suggests that immune parameters may be used as biomarkers of contamination by EDCs. However, caution should be used in the assessment of such immunotoxicity. In particular, more attention should be paid to the specificity of these biomarkers, the external/internal factors influencing the response, and the transduction pathways induced by these molecules in fish. The use of the well-known mammalian models provides a useful guide for future research in fish.

Histopathological and haematological response of male rainbow trout (Oncorhynchus mykiss) subjected to butachlor

“…Also, a reduction in lymphocyte values could be caused by the effects of butachlor as an (anti)androgenic endocrine disruptor, because androgens play a role in haematological homeostasis by mediating lymphocyte proliferation (Milla et al 2011). Conversely, butachlor exposure resulted in an enhancing effect on neutrophil values in the fish.…”

Effects of steroid hormones on reproduction- and detoxification-related gene expression in adult male mosquitofish, Gambusia affinis

“…Endocrine-disrupting compounds (EDCs) are natural and synthetic substances that can interfere with normal hormone signaling pathways by stimulating or inhibiting interactions and cause adverse effects on health and reproduction of animals (Milla et al, 2011). As typical EDCs, steroid hormones have been reported in the aquatic environment (Teles et al, 2006;Zucchi et al, 2012).…”

“…Progesterone (P) was detected at concentrations up to 2060 ng/L in the water column of the Fenholloway River (Jenkins et al, 2003). The presence of these steroid hormones may affect aquatic organisms (Miracle et al, 2006;Davis et al, 2007;Milla et al, 2011;Zucchi et al, 2012). Up to now, most studies in the literature focus on the biological effects caused by estrogens (Teles et al, 2006;Carrera et al, 2007;Davis et al, 2007;Henry et al, 2009;Marlatt et al, 2010;Del Giudice et al, 2011), with relatively few studies having examined the biological effects of other steroid hormones such as androgens and progestins.…”

“…The action of steroid hormones is classically mediated by their receptors, which act as ligand-dependent transcription factors, controlling the transcription of target genes including Vtg genes (Chakraborty et al, 2011;Milla et al, 2011). Therefore, any disruption in the signaling of steroid receptors may lead to impairment of genomic pathways and downstream processes (Milla et al, 2011).…”

Evaluation of estrogenic activity in the Pearl River by using effect-directed analysis

“…There is a long list of chemicals with estrogenic activity, which include natural estrogens excreted from humans and animals, and synthetic or industrial chemicals such as bisphenol A (BPA), 4-tert-octylphenol (4-t-OP), and 4-nonylphenol (4-NP) (Fürhacker et al 2000;Ying et al 2002a, b;Chang et al 2009;Zhang et al 2014). Incomplete removal of these chemicals in wastewater treatment plants may lead to contamination of the receiving aquatic environment (Ying et al 2008;Chang et al 2009;Arditsoglou and Voutsa 2010), which may cause various endocrine-disrupting effects such as feminization of fish (Kawai et al 2003;Jobling et al 2009;Xie et al 2010;Milla et al 2011).…”