Effects of binary mixtures of estrogen and antiestrogens on Japanese medaka (Oryzias latipes)

Abstract

a b s t r a c tIt is supposed that the estrogenic effects of estrogenic chemicals will be balanced by the presence of other endocrine-disrupting chemicals (EDCs) with different properties. However, little convincing research into this issue has been carried out to date. In the present study, the combined effects of EDCs with estrogenic and antiestrogenic activities were assessed using a 21-day reproduction assay with the Japanese medaka (Oryzias latipes) as an in vivo model. Natural estrogen (17␤-estradiol, E2) and the pharmaceutical substances letrozole and tamoxifen, which are both model antiestrogens, were tested as reference compounds individually and in combination. Exposure to E2 (200 ng/L) alone resulted in significant biological changes in paired fish, including impaired reproductive capacity and plasma vitellogenin induction. Upon coexposure with tamoxifen or letrozole (10, 50 and 250 g/L), the effects of estrogen on some biomarkers (e.g., plasma vitellogenin concentration) could be neutralized to some extent, but the impairments in reproductive performance were hardly ameliorated or even became more severe. Since reproductive performance is a more holistic parameter with population-level relevance, the possibility that the effects of estrogenic chemicals can be cancelled out by the presence of antiestrogens in aquatic organisms should be questioned. Our observations also illustrate the importance of considering multiple endpoints at different biological levels of organisms for accurate and adequate assessment of the integrated effects of EDCs, especially in environmentally relevant exposure situations.

The Antiestrogens Tamoxifen and Fulvestrant Abolish Estrogenic Impacts of 17α-ethinylestradiol on Male Calling Behavior of Xenopus laevis

“…Experimental results obtained by exposure to several individual EDCs demonstrate that co-exposure to EDCs with different MOAs can have distinct, divergent outcomes [22], [53]. Estrogenic effects, for example, can be neutralized or reinforced by antiestrogenic exposure, as it was shown in this and several other studies [22], [53].…”

“…Estrogenic effects, for example, can be neutralized or reinforced by antiestrogenic exposure, as it was shown in this and several other studies [22], [53]. Antiestrogenic exposure itself, however, might not exhibit any effects.…”

“…Surface waters are contaminated by surface runoff, inland drainage and sewage discharge [14], [15]. Thus, aquatic vertebrates, like amphibians and fish, are main targets of a vast number of exogenous steroids or steroid-like chemicals [16], [17] and the number of reports about (anti)androgenic and (anti)estrogenic EDCs affecting development and physiology of amphibians [3], [9], [18]–[22]. Most of these publications, however, focus on exposure to EDCs with just one single MOA, while studies examining the effects of simultaneous exposure to EDCs with different MOAs are rare, although they would reflect more real, natural exposure situations.…”

Effects of β‐endosulfan on the growth and reproduction of zebrafish (Danio rerio)

“…In a similar study conducted in zebrafish, no significant effect on the HSI in males or females was found, but the GSI value was significantly higher in males exposed to 0.3 mg/L tribromophenol than in females [29]. Sun et al [30] reported that HSI was significantly increased in male Japanese medaka exposed to 17-b-estradiol (E 2 ) (200 ng/L) [30]. The lack of sensitivity of the HSI and GSI found in the present study suggests that these endpoints might not provide useful information for short-term exposure of adult fish to estrogenic activity.…”

Effects of EDC Mixtures

“…This assumption was tested in a study by assessing 17β-estradiol (E2) and the anti-estrogens letrozole (an aromatase inhibitor) and tamoxifen, individually and in combination, using a 21-day reproduction in vivo assay with the Japanese medaka (Oryzias latipes) (Sun et al, 2009). This assumption was tested in a study by assessing 17β-estradiol (E2) and the anti-estrogens letrozole (an aromatase inhibitor) and tamoxifen, individually and in combination, using a 21-day reproduction in vivo assay with the Japanese medaka (Oryzias latipes) (Sun et al, 2009).…”