Page 1125 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Zearalenone Chapter | 76 1057

VetBooks.ir had maximum milk levels on day 2 of 4.0 and 6.1 ng zeara- hypothalamic hypophysial axis and the luteinizing hor-
mone (LH) surges that lasted for at least 44 days postexpo-
lenone/mL, respectively. This study indicates a minimal
sure. However, zearalenone consumption did not delay the
transmission of zearalenone into the milk and only for a
short period of time after exposure to high concentrations onset of pubertal estrus nor impair conception rates, ovula-
of zearalenone. Because only minimal amounts of zearale- tion rates, or number of fetuses. Slightly older prepubertal
none and its metabolites could be transmitted to the milk gilts (178 days of age and 94 kg) fed 10 mg zearalenone
(Prelusky et al., 1990), most animals and humans start to daily for 2 weeks had suppressed mean serum concentra-
be exposed to zearalenone directly from food, which is the tions of LH, but the onset of puberty and subsequent repro-
main route for zearalenone exposure. duction were not adversely affected (Green et al., 1990).
Following intubations of tritiated-zearalenone into the Gilts treated daily with zearalenone in feed (at a correspond-
crops of 7-week-old broiler chickens, the greatest accu- ing dose of 200 μg/kg body wt) for 8 days revealed distur-
mulation of radioactivity occurred in the liver 30 min bances in the development and maturation of the largest
postadministration, which became a trace of radioactivity ovarian follicles through the activation of an apoptotic-like
by 48 h postadministration (Mirocha et al., 1982). Only process in the granular cells (Zwierzchowski et al., 2005).
zearalenone was detected in muscle tissue at approxi- These authors further suggested that α-zearalenol was the
mately 4 ppb at 48-h postadministration, indicating the chief factor evoking changes in the ovarian follicles in the
zearalenone residues in edible tissue are minimal. first days of intoxication. In a transgenerational toxicity
study in pigs, Schoevers et al. (2012) demonstrated that
zearalenone reduced the quantity of healthy follicles, which
MECHANISM OF ACTION
may have led to premature oocyte depletion in adulthood.
Zearalenone undergoes reduction of the 6 ketone to a In this study, expression of estrogen receptor β mRNA
0
secondary alcohol, which leads to two diastereoisomeric increased following zearalenone exposure, whereas expres-
zearalenols (α and β), which are naturally occurring fun- sion of genes coding for estrogen converting enzymes
gal metabolites. The α-zearalenol metabolite is three remained unchanged.
times more estrogenic than zearalenone, is an anabolic Zhao et al. (2013) emphasized that peripubertal and
growth-promoting compound, zearanol or Ralgro, used in early pregnancy are two sensitive periods that can be
both cattle and sheep commercially. influenced by zearalenone exposure, which affects not
Zearalenone and metabolites can interact directly with only puberty and estrous cyclicity but also early preg-
the cytoplasmic receptor that binds to 17β-estradiol and nancy events, including fertilization, embryo develop-
translocate receptor sites to the nucleus (Katzenellenbogen ment, embryo transport, and embryo implantation.
et al., 1979). In the nucleus, stimulation of RNA leads to Male rats, 70 days old, dosed orally with zearalenone
protein synthesis and clinical signs of estrogenism. at 20 mg/kg body wt for 35 days had elevated serum pro-
Following subcutaneous injection of the compounds, the lactin concentrations but showed no changes in serum
zearalenols and zearalenone stimulated production of a LH and follicle stimulating hormone concentrations,
specific uterine protein and increased uterine weights. body and testes weights, or in spermatogonia, spermato-
Within the resorcylic acids, α-zearalenol exhibited the cytes, and spermatids (Milano et al., 1995). In a recent
greatest binding affinity for cytosolic estrogen receptors, study, Zheng et al. (2016) reported that zearalenone may
while zearalenone and β-zearalanol displayed much lower affect the secretory function of Sertoli cells by disrupting
binding affinities (Fitzpatrick et al., 1989). The hydroxyl- cytoskeletal structure (α-tubulin filaments and F-actin
ation of zearalenone to α-zearalenol apparently is an acti- bundles) and by damaging the nucleus of Sertoli cells,
vation process, whereas the production of β-zearalenol and these effects may be an underlying cause of
would be a deactivation process. The relative binding affin- zearalenone-induced male reproductive toxicity. At rela-
ity of α-zearalenol was greater in the pig than in the rat or tively high concentrations in vitro, approximately
chicken. Interspecies variations and age-related differences 400 μM, zearalenone appeared to act directly on intersti-
in sensitivity to zearalenone in the feed could be related to tial cells of the testes inhibiting steroidogenesis (Fenske
different metabolites produced and the relative binding and Fink-Gremmels, 1990). In a recent in vitro study,
affinities of zearalenone and metabolites formed Liu et al. (2014) demonstrated that zearalenone interferes
(Malekinejad et al., 2006; Haneweer et al., 2007; Parveen with testosterone biosynthesis in mouse Leydig cells via
et al., 2009). the crosstalk of estrogen receptor signaling and orphan
Zearalenone can also act on the hypothala- nuclear receptor Nur77 expression.
mic hypophysial axis. Using 70-day-old Yorkshire gilts While zearalenone primarily affects reproduction, it
(20 27 kg) fed 1.5 2 mg zearalenone/kg feed for appears to have additional effects (such as oxidative stress
45 90 days, Rainey et al. (1990) determined that prepuber- and inflammation) targeting liver, kidney, spleen and
tal exposure to zearalenone affected the blood in weanling piglets (Tiemann and Danicke, 2007;