Toxicological Effects of Regulated Mycotoxins and Persistent Organochloride Pesticides: In Vitro Cytotoxic Assessment of Single and Defined Mixtures on MA-10 Murine Leydig Cell Line

Toxicol In Vitro. 2018 Apr;48:93-103. doi: 10.1016/j.tiv.2017.12.019. Epub 2018 Jan 5.

Abstract

Epidemiological studies show that there is global decline in male fertility primarily as a result of poor sperm quality and this is attributed to exposure to endocrine disrupting chemicals (EDCs) in the environment, food and pharmaceutical products, including mycotoxins and pesticides. The Leydig cells in the male testes are responsible for producing androgens, hormones that play major roles in male development and reproductive function. Therefore, any toxin that affects the function and morphology of the Leydig cells may result in sub-fertility or infertility. The cytotoxic effects of single and binary mixtures of aflatoxin B1 (AFB1), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN), alpha-zearalenol (α-ZOL), beta-zearalenol (β-ZOL), 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (p,p'-DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) on a model cell line, the MA-10 Leydig cells, were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-dipenyltetrazolium bromide (MTT) assay after 48h of exposure. With single toxin treatment at doses between 0.1μM and 64μM for 48h, DON was the most cytotoxic to MA-10 cells with a half maximal inhibitory concentration (IC50) value of 12.3μM followed by α-ZOL (IC50: 28μM) and OTA (IC50: 30μM) while the IC50 of AFB1, p,p'-DDT and p,p'-DDE were above the highest concentration tested (64μM). Co-exposure with p,p'-DDT or p,p'-DDE enhanced the toxicity of DON, OTA and ZEN to MA-10 Leydig cells, particularly at higher concentrations. This highlights the possible adverse effects on male reproductive health following co-exposure to these toxins.

Keywords: Cytotoxicity; Leydig cells; MA-10 cell line; Mixture toxicity; Mycotoxins; Pesticides; Reproductive toxicity.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Endocrine Disruptors / toxicity
  • Hydrocarbons, Chlorinated / toxicity*
  • Infertility, Male / chemically induced
  • Infertility, Male / pathology
  • Leydig Cells / drug effects*
  • Male
  • Mice
  • Mycotoxins / toxicity*
  • Pesticide Residues / toxicity
  • Pesticides / toxicity*

Substances

  • Endocrine Disruptors
  • Hydrocarbons, Chlorinated
  • Mycotoxins
  • Pesticide Residues
  • Pesticides