Equol Induces Gonadal Intersex In Japanese Medaka (Oryzias Latipes) At Environmentally Relevant Concentrations: Comparison With 17 Beta-Estradiol

Equol is present in the aquatic environment via livestock waste and runoff discharge; however, it remains unclear whether it can induce gonadal intersex in fish at environmentally relevant concentrations. This study evaluated adverse effects of equol on gonadal development by exposing transgenic Japanese medaka (Olyzias latipes) from hatching for 100 days. Equol induced intersex incidence in male medaka in a dose-dependent manner, and the benchmark dose corresponding to 10% intersex incidence (BMD10) was 11.5 ng/L (95% confidence interval (CI): 5.8 ng/L, 19.8 ng/L), which was comparable to the required dose of 17 beta-estradiol (E2 beta) (9.0 ng/L, 95% CI: 6.6 ng/L, 11.0 ng/L). Equol exposure resulted in reduced plasma 11-ketotestosterone (11-KT) concentrations in male medaka at 1.3 ng/L, while reduced plasma 11-KT concentrations were observed at a relatively high concentration (6.4 ng/L) of E2 beta. Such antiandrogenic property could partly explain the comparable potency of equol with that of E2 beta to induce intersex at relatively low concentrations, although the binding affinity of equol to medaka estrogen receptor alpha (EC50 939.4 nM) was 230 fold lower than that (4.07 nM) of E2 beta. This study for the first time demonstrated that equol could induce intersex in medaka fish at environmentally relevant concentrations.