The anti-androgenic effect of chronic exposure to semicarbazide on male Japanese flounder (Paralichthys olivaceus) and its potential mechanisms

Abstract

Semicarbazide (SMC), a new marine pollutant, has anti-estrogenic effects on female Japanese flounder (Paralichthys olivaceus). However, whether SMC also affects the reproductive endocrine system of male marine organisms is currently unclear. In this study, Japanese flounder embryos were exposed to 1, 10, and 100 μg/L SMC for 130 days. Plasma testosterone (T) and 17β-estradiol (E2) concentrations were significantly decreased in male flounders after SMC exposure. The expression of genes involved in T and E2 synthesis, including steroidogenic acute regulatory protein, cytochrome P450 11A1, 17α-hydroxylase, 17β-hydroxysteroid dehydrogenase and cytochrome P450 19A, was down-regulated in the gonads, which may explain the decrease in plasma sex hormones levels. Moreover, SMC-mediated changes in the transcription of these steroidogenic genes were associated with reduced levels of follicle-stimulating hormone beta subunit (fshβ), luteinizing hormone beta subunit (lhβ), follicle-stimulating hormone receptor (fshr) and luteinizing hormone receptor (lhr) mRNA. In addition, down-regulated transcription of fshβ and lhβ in the SMC exposure groups was affected by reduced mRNA levels of seabream gonadotropin-releasing hormone (sbgnrh), g-protein-coupled receptor 54 (gpr54) in the kisspeptin/gpr54 system, as well as the gamma-aminobutyric acid (GABA) synthesis enzyme glutamic acid decarboxylase (gad). Overall, our results showed that environmentally relevant concentrations of SMC exerted anti-androgenic effects in male flounders via impacting HPG axis, kiss/gpr54 system and GABA synthesis, providing theoretical support for investigating reproductive toxicity of environmental pollutants that interfere with the neuroendocrine system.