Comparative Cytotoxic Effects and Possible Mechanisms of Deoxynivalenol, Zearalenone and T-2 Toxin Exposure to Porcine Leydig Cells In Vitro

Abstract

Mycotoxins such as zearalenone (ZEN), deoxynivalenol (DON) and T-2 toxin (T-2) are the most poisonous biological toxins in food pollution. Mycotoxin contaminations are a global health issue. The aim of the current study was to use porcine Leydig cells as a model to explore the toxic effects and underlying mechanisms of ZEN, DON and T-2. The 50% inhibitory concentration (IC50) of ZEN was 49.71 μM, and the IC50 values of DON and T-2 were 2.49 μM and 97.18 nM, respectively. Based on the values of IC50, ZEN, DON and T-2 exposure resulted in increased cell apoptosis, as well as disrupted mitochondria membrane potential and cell cycle distribution. The results also showed that ZEN and DON significantly reduced testosterone and progesterone secretion in Leydig cells, but T-2 only reduced testosterone secretion. Furthermore, the expression of steroidogenic acute regulatory (StAR) protein and 3β-hydroxysteroid dehydrogenase (3β-HSD) were significantly decreased by ZEN, DON and T-2; whereas the protein expression of cholesterol side-chain cleavage enzyme (CYP11A1) was only significantly decreased by ZEN. Altogether, these data suggest that the ZEN, DON and T-2 toxins resulted in reproductive toxicity involving the inhibition of steroidogenesis and cell proliferation, which contributes to the cellular apoptosis induced by mitochondrial injury in porcine Leydig cells.

Carry-Over of Zearalenone and Its Metabolites to Intestinal Tissues and the Expression of CYP1A1 and GSTπ1 in the Colon of Gilts before Puberty

“…In the ascending colon, on D1 and D3, CYP1A1 m RNA expression was most strongly silenced in group C in comparison with the experimental groups. Similar results were reported by Sun et al [ 6 ] in Leydig cells exposed in vitro to ZEN. In the ascending colon, on D1 and D3, CYP1A1 m RNA expression was most strongly silenced in group C (1.226 and 0.623, respectively).…”

“…This is because the duodenum and jejunum have firmly adherent mucus and polysaccharide layers [ 38 ], and prepubertal gilts have high requirements for estrogen and estrogenic compounds [ 5 ] due to supraphysiological hormonal levels [ 39 ]. In groups ZEN10 and ZEN15, higher ZEN concentrations could also be attributed to the presence of “free ZEN”, which contributes to: (i) the inhibition of steroidogenesis [ 6 ]; (ii) the conversion of testosterone (ZEN suppresses testosterone levels) to estradiol (which inhibits maturation processes in prepubertal gilts, [ 40 ]); and (iii) increased feed intake and the accumulation of energy [ 7 ], supporting homeostasis and, at later procreation of the organism, reproduction in prepubertal gilts [ 41 ]. It should also be noted that the period of adaptation to an ongoing mycotoxicosis ends after seven dates of exposure (i.e., on D1) [ 42 ].…”

“…The CF is the concentration ratio of the undesirable substances (mycotoxin) in contaminated digesta to the concentrations of ZEN and its metabolites in gut tissues, which marks the beginning of biotransformation processes. Our previous research demonstrated that even MABEL doses can induce specific changes in homeostasis [ 52 ], metabolic processes [ 7 ], endocrine processes [ 5 , 6 ], and gut microbiota [ 8 ] in prepubertal gilts.…”

“…A different trend was noted in group ZEN10 in the duodenum, where ZEN is most easily and rapidly absorbed [ 38 ]. These values were sufficient to induce considerable disruptions in metabolic processes [ 18 ] and, most importantly, steroidogenesis [ 6 , 20 , 53 , 54 ] via estrogen receptors [ 4 , 52 ]. These findings confirm that the effects exerted by mycotoxins applied at low doses have not been fully elucidated in prepubertal females.…”

“…This promiscuous compound induces the expression of estrogen receptors [ 4 ], contributes to reproductive disorders, and can even lead to changes in reproductive organs. Zearalenone also disrupts the hormonal balance [ 2 , 5 , 6 ], metabolic profile [ 7 ], and gut microbiota [ 8 ]. It exerts hepatotoxic [ 9 , 10 ], immunotoxic [ 11 ], hematotoxic [ 12 ], and genotoxic effects [ 13 ].…”