Chronic Exposure of Marine Medaka (Oryzias melastigma) to 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) Reveals Its Mechanism of Action in Endocrine Disruption via the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis

Abstract

In this study, marine medaka (Oryzias melastigma) were chronically exposed for 28 days to environmentally realistic concentrations of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) (0, 0.76, 2.45, and 9.86 μg/L), the active ingredient in commercial antifouling agent SeaNine 211. Alterations of the hypothalamus-pituitary–gonadal-liver (HPGL) axis were investigated across diverse levels of biological organization to reveal the underlying mechanisms of its endocrine disruptive effects. Gene transcription analysis showed that DCOIT had positive regulatory effects mainly in male HPGL axis with lesser extent in females. The stimulated steroidogenic activities resulted in increased concentrations of steroid hormones, including estradiol (E2), testosterone (T), and 11-KT-testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in hormone homeostasis and increased E2/T ratio. The relatively estrogenic intracellular environment in both sexes induced the hepatic synthesis and increased the liver and plasma content of vitellogenin (VTG) or choriogenin. Furthermore, parental exposure to DCOIT transgenerationally impaired the viability of offspring, as supported by a decrease in hatching and swimming activity. Overall, the present results elucidated the estrogenic mechanisms along HPGL axis for the endocrine disruptive effects of DCOIT. The reproductive impairments of DCOIT at environmentally realistic concentrations highlights the need for more comprehensive investigations of its potential ecological risks.

High-throughput transcriptome sequencing reveals the combined effects of key e-waste contaminants, decabromodiphenyl ether (BDE-209) and lead, in zebrafish larvae

“…Although hatching enzymes, needed to hydrolyze the chorion (Chen et al, 2016), were consistently inhibited in all exposure treatments, hatching success did not change significantly compared to the control. However, adverse effects on angiogenesis, a process involved in blood vessel growth, were reflected in terms of the increased heart rates of the zebrafish larvae.…”

Transgenerational endocrine disruption and neurotoxicity in zebrafish larvae after parental exposure to binary mixtures of decabromodiphenyl ether (BDE-209) and lead

“…After parental exposure to the control, 1 mg/L BDE-209, 10 mg/L Pb, or their binary mixture for 3 months, approximately 300 offspring larvae at 5 dpf were collected to profile the differential abundances of proteins using shotgun proteomics (n ¼ 3) (Chen et al, 2016b). The samples were homogenized in lysis buffer (8 M urea and 40 mM HEPES, pH 7.4) on ice using a Misonix Sonicator-XL2020 (Misonix, NY, USA).…”

Norethindrone alters growth, sex differentiation and gene expression in marine medaka (Oryzias melastigma)

“…The primers of target genes, including gnrh , gtha , gnrhr2 , fshb , lhβ , cyp19a1b , cyp17a , star , fshr , lhr , cyp19a1a , cyp11b , cyp11a , 3βhsd , 17βhsd , vtgr , ara , era , erβ chgh , chgl , vtg 1 and vtg 2 35,39–42 associated with the HPG axis, pgr and pr are listed in Table S1. In addition, two control genes ( actb2 and rpl7 ) were used to normalize the transcriptional expression levels of target genes 39,43,44 .…”

“…Due to the compound effect of salinity on the activity of pollutants, the experiments in freshwater fish may not be able to accurately assess the ecological risk of the NET in the ocean 34 . Marine medaka ( Oryzias melastigma ) is a small euryhaline fish, which is widely used in monitoring toxicity in aquatic environments 35–37 . In this study, long‐term exposure to NET was used to evaluate the effect of NET on the growth, sexual differentiation, gonadal histology, and transcriptional expression of genes related to the HPG axis.…”