Effects of Fish Oil on 2,3,7,8-Tetrachlorodibenzo-para-dioxin and Polychlorinated Biphenyl 126 Toxicity on the Male Reproductive System of C57BL/6J Mice

Abstract

Abstract Background: Dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) are a group of contaminants associated with a wide range of adverse health effects. In 2018, the European Food Safety Authority (EFSA) reevaluated the toxicity of this group of contaminants, identifying their significant effects on the male reproductive system. Consequently, EFSA reduced the tolerable weekly intake (TWI) from 14 to 2 pg WHO2005-Toxic Equivalents (TEQ)/kg bw/week. A central source of exposure to these contaminants is fish, especially fatty fish. Still, the Norwegian Directorate of Health recommend including fish in the diet because of its nutritional benefits such as n-3 polyunsaturated fatty acids, resulting in an increased exposure to dioxins and dl-PCBs. Aim: The main aim of the thesis was to evaluate how a dietary intake of marine-derived nutrients and contaminants affected the male reproductive system in mice, concentrating on the sperm quality. Methods: Male C57BL/6J mice were included in a fractional factorial experiment of 13 weeks and fed diets consisting of three levels of fish oil (0%, 1%, or 5%) and three levels of contaminants (control, low, or high dose). The contaminants used were 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or PCB-126. Physiological parameters were measured throughout the trial, including body weight and composition, feed intake and hematology. Cauda epididymal sperm concentration, motility and morphology were assessed by Computer Assisted Sperm Analyzer, in addition to a manual sperm count. Serum testosterone levels were measured, and gene expression levels in epididymis were assessed. Results: TCDD and PCB-126 did not influence the sperm quality in the mice, independent of dose. The mice fed high levels of fish oil showed a tendency of reduced motility, in addition to an enlargement of the spermatozoa. Mice fed high doses of TCDD or PCB-126 had a significant elevated gene expression of CYP1A1 in epididymis, higher liver weights and reduced fat mass, all compared to control groups. In addition, mice fed TCDD had a reduced body weight gain and altered hematology compared to control groups. In the mice fed high dose TCDD and high level of fish oil, fish oil significantly reduced the gene expression level of CYP1A1. Conclusion: Fish oil did not influence the toxicity of the contaminants on the general health of the mice. TCDD and PCB-126 did not affect the sperm quality, but high levels of fish oil had an impact on the sperm quality.