Disruption of the gonadal endocannabinoid system in zebrafish exposed to diisononyl phthalate

Abstract

DiNP (Di-isononyl phthalate) has been recently introduced as DEHP (Bis (2-ethylhexyl) phthalate) substitute and due to its chemical properties, DiNP is commonly used in a large variety of plastic items. The endocannabinoid system (ECS) is a lipid signaling system involved in a plethora of physiological pathways including the control of the reproductive and metabolic processes. In this study, the effects of DiNP on the ECS of zebrafish (male and female) gonads were analyzed. Adult zebrafish were chronically exposed for 21 days via water to 3 environmentally relevant concentrations of DiNP (42 μg/L; 4.2 μg/L; 0.42 μg/L). In females, the Gonadosomatic Index (GSI) and the number of fertilized eggs were reduced by the lowest concentration of DiNP tested. The levels of two endocannabinoids, Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG), were not affected, while a reduction of the N-oleoyl-ethanolamine (OEA) level was observed. Transcriptional changes were reported in relation to genes coding for the ECS receptors and the enzymes involved in the ECS pathway. DiNP exposure in males reduced the GSI as well as changed the levels of endocannabinoids. Moreover, DiNP treatment induced significative changes in the genes coding for the ECS receptors and enzymes, and significantly increased the activity of the fatty acid amide hydrolase (FAAH). In summary, in zebrafish, exposure to environmentally relevant concentrations of DiNP disrupted the ECS and affected reproduction in a gender specific manner.