Exposure to monocrotophos pesticide causes disruption of the hypothalamic-pituitary-thyroid axis in adult male goldfish (Carassius auratus)

Abstract

The thyroid hormones (THs) 3,3',5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic-pituitary-thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone β subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis.

Keywords: 17β-estradiol; 3,3′,5,5′-l-thyroxine; 3,3′,5-triiodo-l-thyronine; 3,3′,5′-triiodo-l-thyronine; 3,3′-T(2); 3,3′-diiodo-l-thyronine; ANOVA; CRH; D1; D2; D3; Deiodinases; E(2); ESI; FT(3); FT(4); HE; HPG axis; HPI axis; HPT axis; Hypothalamic–pituitary–thyroid axis; IRD; MCP; Male goldfish (Carassius auratus); Monocrotophos; ORD; PBDEs; PCBs; PCZ; PTU; RIA; T; T(3); T(4); THs; TRH; TSH; TT(3); TT(4); TTR; Thyroid hormones; UPLC-MS/MS; VTG; corticotropin-releasing hormone; electrospray ionization source; free T(3); free T(4); hematoxylin and eosin; hypothalamic–pituitary–gonadal axis; hypothalamic–pituitary–interrenal axis; hypothalamic–pituitary–thyroid axis; inner-ring deiodination; monocrotophos; one-way analysis of variance; outer-ring deiodination; polybrominated diphenyl ethers; polychlorinated biphenyls; prochloraz; propylthiouracil; rT(3); radioimmunoassay; testosterone; thyroid hormones; thyroid stimulating hormone; thyrotropin-releasing hormone; total T(3); total T(4); transthyretin; type I deiodinase; type II deiodinase; type III deiodinase; ultra performance liquid chromatography-tandem quadrupole mass spectrometry; vitellogenin.