Effect of dietary zearalenone on the performance, reproduction tract and serum biochemistry in young rats (original) (raw)

Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring

Toxins, 2017

Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed) on gestational days (GDs) 0-21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine laye...

Prenatal exposure to zearalenone disrupts reproductive potential and development via hormone-related genes in male rats

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2018

The present study investigated the reproductive and developmental toxicity of male offspring induced by prenatal ZEN exposure and explored the possible mechanism. 64 pregnant rats were allocated into four groups and fed with ZEN contaminated (0, 5, 10 and 20 mg/kg) diet during the whole gestation period. The results showed that, F1 male foetal viability was not affected while newborn bodyweight (BW) was significantly decreased after prenatal exposure to ZEN. Decreased BW was found on postnatal day (PND) 21 but not on PND 63 in ZEN exposed male rats. Moreover, adult testis weight increased with seminiferous tubules atrophy as well as decreased spermatocytes and mature sperms (35% and 31%) in ZEN-treated rats. Meanwhile, circulating levels of luteinizing hormone and testosterone decreased while estradiol increased in ZEN-treated rats. These impairments concurred with down-regulations of 3β-HSD and StAR in both mRNA and protein levels in weaned and adult testis. Furthermore, gene and p...

The Effect of Low Monotonic Doses of Zearalenone on Selected Reproductive Tissues in Pre-Pubertal Female Dogs—A Review

Molecules, 2015

The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose theory of estrogen-like compounds, hormesis, NOAEL dose, compensatory response and/or food tolerance, and effects of exposure to undesirable substances. The above considerations increased the researchers' interest in risk evaluation, namely: (i) clinical symptoms associated with long-term, daily exposure to low doses of a toxic compound; and (ii) dysfunctions at cellular or tissue level that do not produce clinical symptoms. Research advancements facilitate the extrapolation of results and promote the use of novel tools for evaluating the risk of exposure, for example exposure to zearalenone in pre-pubertal female dogs. The arguments presented in this paper suggest that low doses of zearalenone in commercial feeds stimulate metabolic processes and increase weight gains. Those processes are accompanied by lower proliferation rates in the ovaries, neoangiogenesis and vasodilation in the ovaries and the uterus, changes in the steroid hormone profile, and changes in the activity of hydroxysteroid dehydrogenases. All of the above changes result from exogenous hyperestrogenizm.

Zearalenone effect on uterine weight of rats

Agriculturae Conspectus Scientificus, 2012

Mycotoxins are today considered one of the main contaminants of food and feed. Widespread zearalenone and its metabolites have potent estrogenic and anabolic activity, proven in numerous studies worldwide. Th e aim is to investigate infl uence of zearalenone on the uterine weight of rats depending on the applied dose and duration of the observation period. In a controlled experimental study, 63 adult female Wistar rats were divided into three groups, depending on the oral test dose of zearalenone applied: 0.1, 0.3 and 0.5 mg / kg of body weight. At the end of each of the four observation periods of seven days, animals were sacrifi ced under general anesthesia with ether, and aft er an autopsy the mass of the uterus was determined. Zearalenone in the dose of 0.1 mg / kg of body weight has caused a signifi cant increase in uterine weight between the fi rst and fourth observation interval. Doses of 0.3 and 0.5 mg zearalenone / kg caused a decrease in uterine weight, which was at a dose of 0.5 mg / kg highly signifi cant between all observational intervals. Aft er 7 days of applying of the toxin, uterine weights did not diff er signifi cantly with respect to applied dose. Aft er 14, 21 and 28 days, diff erences in uterine weight were highly signifi cant, depending on the dose of zearalenone. Th e results show that prolonged application of large doses of zearalenone produced a signifi cant decrease in uterine weights in experimental animals.

The effects of zearalenone on reproduction in swine. I. The relationship between ingested zearalenone dose and anestrus in non-pregnant, sexually mature gilts

Theriogenology, 1987

Ninety-nine sexually mature, non-pregnant gilts were checked for estrus daily with a mature boar and then allocated at estrus (D 0) to receive 2 kg/d of a diet containing 0, 1, 5 or 10 ppm purified zearalenone between D 5 and 20 of the estrous cycle during two seasons of the year (winter and summer). None of the gilts exhibited any visual signs of "hyperestrogenism" and there was no effect of season on interestrous interval (P > 0.05). A significant effect of zearalenone dose on inter-estrous interval was detected (P < 0.001). Gilts receiving 0 or 1 ppm had similar inter-estrous intervals (21.0 + 0.3 and 21.5 2 0.8 d, respectively) whereas gilts receiving 5 and 10 ppm had extended cycles (29.2 + 2.9 and 32.7 + 3.3 d, respectively). Plasma progesterone concentrations at D 19 to 21 were higher in gilts with extended cycles (P ,< 0.001) and corpora lutea (CL) were present at laparotomy. Some 86% of these retained CL underwent spontaneous regression resulting in the onset of estrus within the next 30 d. Fecal zearalenone concentrations rose during ingestion of contaminated diets and declined to pretreatment values within 2 d (1 ppm) to 8 d (10 ppm) of the cessation of treatment. These data show that feeding zearalenone at concentrations of 5 to 10 ppm from D 5 to 20 of the estrous cycle causes luteal mai.ntenance and extended inter-estrous intervals. Spontaneous regression of these CL usually occurs within 30 d after zearalenone is removed from the diet. Fecal zearalenone analysis does not appear to be an effective method for determining prior exposure to zearalenone when carried out more than a lew days following the last ingestion of zearalenone.

Estrogenic and Non-Estrogenic Disruptor Effect of Zearalenone on Male Reproduction: A Review

International Journal of Molecular Sciences

According to some estimates, at least 70% of feedstuffs and finished feeds are contaminated with one or more mycotoxins and, due to its significant prevalence, both animals and humans are highly likely to be exposed to these toxins. In addition to health risks, they also cause economic issues. From a healthcare point of view, zearalenone (ZEA) and its derivatives have been shown to exert many negative effects. Specifically, ZEA has hepatotoxicity, immunotoxicity, genotoxicity, carcinogenicity, intestinal toxicity, reproductive toxicity and endocrine disruption effects. Of these effects, male reproductive deterioration and processes that lead to this have been reviewed in this study. Papers are reviewed that demonstrate estrogenic effects of ZEA due to its analogy to estradiol and how these effects may influence male reproductive cells such as spermatozoa, Sertoli cells and Leydig cells. Data that employ epigenetic effects of ZEA are also discussed. We discuss literature data demonst...

In utero Exposure of Fisher 344 Rats to Low Doses of Zeranol via the Maternal Diet Produces Dose-Dependent Effects on Sexual Development and Reproduction

Abstract. Zeranol is a semi-synthetic derivative of zearalenone, a mycotoxin produced by Fusarium fungi that contaminate grain. Zeranol is a potent mycoestrogen with activity comparable to that of diethylstilbestrol, a synthetic estrogen previously used to prevent miscarriages in at risk women. Diethylstilbestrol was also used in livestock for many years to enhance meat production. Zeranol was developed as a replacement for diethylstilbestrol after human studies demonstrated that children and grandchildren of pregnant mothers who took the drug had an increased risk of cancer. Although zeranol has been used for more than 40 years in the USA and many other countries to enhance meat production and quality, its use is banned in the European Union and many Asian countries. Most human exposures to zeranol occurs result from consumption of contaminated meat and grain. Previous studies showed that both zearaleneone and zeranol are efficiently absorbed from the diet and are readily transport...

Transgenerational toxicity of Zearalenone in pigs

Reproductive Toxicology, 2012

Zearalenone (ZEN) is a mycotoxin that can be a contaminant of food and feed commodities. ZEN acts as a xenoestrogen and is considered an endocrine disruptor. Since estrogens influence oogenesis during fetal growth, the effect of ZEN on oocytes was investigated in the F1-generation. Pregnant and lactating pigs were exposed to feed naturally contaminated with ZEN (200, 500 and 1000 g/kg feed). Ovaries of F1-animals were examined for follicle development, expression of estrogen converting enzymes and estrogen receptors, and oocyte quality. In F1-newborns, ZEN did not affect follicle dynamics, but follicle integrity decreased with increasing ZEN concentrations. Expression of estrogen receptor beta mRNA increased following ZEN exposure, whereas expression of genes coding for estrogen converting enzymes remained unchanged. In F1-prepubertal gilts, follicular atresia and oocyte maturation with subsequent embryo development remained unchanged. In conclusion, ZEN reduced the quantity of healthy follicles, which may lead to premature oocyte depletion in adulthood.

The metabolism of zearalenone in subcellular fractions from rabbit and hen hepatocytes and its estrogenic activity in rabbits

Toxicology, 1986

The in vitro reduction of zearalenone (ZEN) by subcellular fractions from hen and rabbit hepatocytes clearly shows species-specific differences in the cofactor requirements, rate of metabolism and production of metabolites. The presence of NADH as cofactor in the reaction mixtures enhanced only the reducing activity of the microsomal fraction from rabbit hepatocytes, while NADPH enhanced the reducing activities of the cytosolic fraction from rabbit and both the microsomal and cytosolic fractions from hen hepatocytes. Furthermore, we observed that hen hepatocytes metabolize faster and produce ~-zearalenol (ZEL) as the major metabolite, whereas rabbit hepatocytes metabolize ZEN slowly and mainly into a-ZEL, the more uterotrophic metabolite. These last findings are closely related to the higher sensitivity to ZEN estrogenic effects observed in rabbits during the toxicity test involving p.o. administration of the mycotoxin to the animals at 3 dosage levels (0.1, 1, 2 mg/kg body wt).

The Effect of Different Doses of Zearalenone in Feed on the Bioavailability of Zearalenone and Alpha-Zearalenol, and the Concentrations of Estradiol and Testosterone in the Peripheral Blood of Pre-Pubertal Gilts

Toxins

The objective of this study was to determine the effect of long-term (48 days), per os administration of specific zearalenone (ZEN) doses (20 and 40 μg ZEN/kg BW in experimental groups EI and EII, which were equivalent to 200% and 400% of the upper range limit of the no-observed-adverse-effect-level (NOAEL), respectively) on the bioavailability of ZEN and the rate of changes in estradiol and testosterone concentrations in the peripheral blood of pre-pubertal gilts. ZEN and α-ZEL levels were similar until day 28. After day 28, α-ZEL concentrations increased significantly in group EI, whereas a significant rise in ZEN levels was noted in group EII. The presence of estradiol in peripheral blood plasma was not observed until day 20 of the experiment. Spontaneous secretion of estradiol was minimal, and it was determined at very low levels of up to 10 pg/mL in EI and EII groups. Testosterone concentrations ranged from 4 to 9 ng/mL in all groups. A decrease in the concentrations of both an...