Zearalenone damages the male reproductive system of rats by destroying testicular focal adhesion.

Zearalenone (ZEA), a common mycotoxin in animal feed, is harmful to public health and causes huge economic losses. The potential target proteins of ZEA and its derivatives were screened using the PharmMapper database and the related genes (proteins) of the testis were obtained from Genecards. We obtained 144 potential targets of ZEA and its derivatives related to the testis using Venn diagrams. The PPI analysis showed that ZEA had the most targets in testis, followed by ZAN, α-ZAL, ß-ZEL, α-ZEL, and ß-ZAL. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses evaluated the metabolic and cancer pathways. We further screened four hub genes: RAC3, CCND1, EP300, and CTNNB1. Eight key biological processes were obtained by GO analysis, and four important pathways were identified by KEGG analysis. Animal and cell experimental results confirmed that ZEA could inhibit the expression of four key KEGG pathway protein components and four hub proteins that interfere with cell adhesion by inhibiting the focal adhesion structure of the testis, Leydig cells, and Sertoli cells. Collectively, our findings reveal that the destruction of the focal adhesion structure in the testis is the mechanism through which ZEA damages the male reproductive system.

The Effects of Zearalenone on the Localization and Expression of Reproductive Hormones in the Ovaries of Weaned Gilts.

This study aims to investigate the effects of zearalenone (ZEA) on the localizations and expressions of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), gonadotropin releasing hormone (GnRH) and gonadotropin releasing hormone receptor (GnRHR) in the ovaries of weaned gilts. Twenty 42-day-old weaned gilts were randomly allocated into two groups, and treated with a control diet and a ZEA-contaminated diet (ZEA 1.04 mg/kg), respectively. After 7-day adjustment, gilts were fed individually for 35 days and euthanized for blood and ovarian samples collection before morning feeding on the 36th day. Serum hormones of E2, PRG, FSH, LH and GnRH were determined using radioimmunoassay kits. The ovaries were collected for relative mRNA and protein expression, and immunohistochemical analysis of FSHR, LHR, GnRH and GnRHR. The results revealed that ZEA exposure significantly increased the final vulva area (p < 0.05), significantly elevated the serum concentrations of estradiol, follicle stimulating hormone and GnRH (p < 0.05), and markedly up-regulated the mRNA and protein expressions of FSHR, LHR, GnRH and GnRHR (p < 0.05). Besides, the results of immunohistochemistry showed that the immunoreactive substances of ovarian FSHR, LHR, GnRH and GnRHR in the gilts fed the ZEA-contaminated diet were stronger than the gilts fed the control diet. Our findings indicated that dietary ZEA (1.04 mg/kg) could cause follicular proliferation by interfering with the localization and expression of FSHR, LHR, GnRH and GnRHR, and then affect the follicular development of weaned gilts.

Obesity alters the ovarian proteomic response to zearalenone exposure†.

Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, is detrimental to female reproduction. Altered chemical biotransformation, depleted primordial follicles and a blunted genotoxicant response have been discovered in obese female ovaries, thus, this study investigated the hypothesis that obesity would enhance ovarian sensitivity to ZEN exposure. Seven-week-old female wild-type nonagouti KK.Cg-a/a mice (lean) and agouti lethal yellow KK.Cg-Ay/J mice (obese) received food and water ad libitum, and either saline or ZEN (40 µg/kg) per os for 15 days. Body and organ weights, and estrous cyclicity were recorded, and ovaries collected posteuthanasia for protein analysis. Body and liver weights were increased (P < 0.05) in the obese mice, but obesity did not affect (P > 0.05) heart, kidney, spleen, uterus, or ovary weight and there was no impact (P > 0.05) of ZEN exposure on body or organ weight in lean or obese mice. Obese mice had shorter proestrus (P < 0.05) and a tendency (P = 0.055) for longer metestrus/diestrus. ZEN exposure in obese mice increased estrus but shortened metestrus/diestrus length. Neither obesity nor ZEN exposure impacted (P > 0.05) circulating progesterone, or ovarian abundance of EPHX1, GSTP1, CYP2E1, ATM, BRCA1, DNMT1, HDAC1, H4K16ac, or H3K9me3. Lean mice exposed to ZEN had a minor increase in γH2AX abundance (P < 0.05). In lean and obese mice, LC-MS/MS identified alterations to proteins involved in chemical metabolism, DNA repair and reproduction. These data identify ZEN-induced adverse ovarian modes of action and suggest that obesity is additive to ZEN-induced ovotoxicity.

Occurrence, Impact on Agriculture, Human Health, and Management Strategies of Zearalenone in Food and Feed: A Review.

Mycotoxins represent an assorted range of secondary fungal metabolites that extensively occur in numerous food and feed ingredients at any stage during pre- and post-harvest conditions. Zearalenone (ZEN), a mycotoxin categorized as a xenoestrogen poses structural similarity with natural estrogens that enables its binding to the estrogen receptors leading to hormonal misbalance and numerous reproductive diseases. ZEN is mainly found in crops belonging to temperate regions, primarily in maize and other cereal crops that form an important part of various food and feed. Because of the significant adverse effects of ZEN on both human and animal, there is an alarming need for effective detection, mitigation, and management strategies to assure food and feed safety and security. The present review tends to provide an updated overview of the different sources, occurrence and biosynthetic mechanisms of ZEN in various food and feed. It also provides insight to its harmful effects on human health and agriculture along with its effective detection, management, and control strategies.

Evaluation of immunomodulatory effects of zearalenone in mice.

Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin produced by Fusarium species. The toxicity of ZEA has been evaluated for reproductive and developmental effects; however, there is little evidence about its acute toxicity or general immunotoxicity. In the present study, immune regulatory functions were investigated in mice that had been exposed to ZEA (5 or 20 mg/kg BW) daily for 14 days. Results showed that sub-populations of CD4+, CD8+ and CD11c+ cells in the spleen and CD4+, CD8+ and F4/80+ cells in the mesenteric lymph nodes (MLN) of ZEA (20 mg/kg)-exposed hosts were decreased compared to those in the control mice. However, CD19+ and CD11c+ cells were increased in the MLN of the ZEA mice and CD4+CD25+Foxp3+ cells were decreased in the spleen and MLN. There were differential changes in the immune cell populations of the small intestine of the ZEA mice as well, depending on small intestine location. In ex vivo experiments, ZEA treatments resulted in increased proliferative capacities of mitogen-induced splenocytes and MLN cells; such changes were paralleled by significant increases in interferon (IFN)-γ production. With regard to serum isotypes, IgM levels were decreased and IgE levels were increased in the 20 mg/kg ZEA-treated mice. Mucosal IgA levels were decreased in the duodenum and vagina of these hosts. Serum analyzes also revealed that tumor necrosis factor (TNF)-α levels were decreased and interleukin (IL)-6 levels increased as a result of ZEA exposures. ZEA treatment also led to increased apoptosis in the spleen and Peyer's patches; these changes were associated with changes in the ratios of Bax:Bcl-2. Following priming with different TLR ligands, ZEA exposure led to differentially modulated TLR signaling and variable production of pro- and anti-inflammatory cytokines in RAW 264.7 macrophage cells. Taken together, these results indicated that ZEA could alter the normal expression/function of different immune system components and this would likely lead to immunomodulation in situ.

The Protective Effect of Grape-Seed Proanthocyanidin Extract on Oxidative Damage Induced by Zearalenone in Kunming Mice Liver.

Although grape-seed proanthocyanidin extract (GSPE) demonstrates strong anti-oxidant activity, little research has been done to clearly reveal the protective effects on the hepatotoxicity caused by zearalenone (ZEN). This study is to explore the protective effect of GSPE on ZEN-induced oxidative damage of liver in Kunming mice and the possible protective molecular mechanism of GSPE. The results indicated that GSPE could greatly reduce the ZEN-induced increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. GSPE also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD and GSH-Px. The analysis indicated that ZEN decreased both mRNA expression levels and protein expression levels of nuclear erythroid2-related factor2 (Nrf2). Nrf2 is considered to be an essential antioxidative transcription factor, as downstream GSH-Px, γ-glutamyl cysteine synthetase (γ-GCS), hemeoxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) decreased simultaneously, whereas the pre-administration of GSPE groups was shown to elevate these expressions. The results indicated that GSPE exerted a protective effect on ZEN-induced hepatic injury and the mechanism might be related to the activation of the Nrf2/ARE signaling pathway.

Alleviation of zearalenone toxicity by modified halloysite nanotubes in the immune response of swine.

Zearalenone (ZEN) has caused significant economic effects on swine production in China. There is growing concern that exposure to ZEN during pregnancy affects the health of the offspring due to changes in the development of the immune system. To assess the risks associated with maternal ZEN exposure, several immunological parameters were assessed in pregnant sows and their offspring. The main aim of the study was to determine if modified hallosite nanotubes (MHNTs) can be used to protect pigs against the adverse effects of ZEN. Eighteen pregnant sows (second parity Yorkshire sows) were randomly divided into three treatment groups: (1) basal diet (control group); (2) contaminated grain (instead of 50% mouldy corn); and (3) contaminated grain (instead of 50% mouldy corn) + 1% MHNTs. The pregnant sows were fed the different treated diets from days 35 to 70 of gestation. Dietary ZEN exposure decreased the organ coefficient and the mRNA expression levels of IFN-γ, TNF-α, and IL-10, and increased ZEN residues and IL-4 mRNA expression in the spleen of pregnant sows and neonatal piglets. Decreases in the serum IgA and IgG levels were observed in the pregnant sows. Maternal ZEN exposure decreased the organ coefficient and the mRNA expression levels of IFN-γ and IL-10, and increased IL-4 mRNA expression in the spleen of weaning piglets. Exposure to ZEN during pregnancy decreased the level of serum IgG in the weaning piglets. Maternal exposure to ZEN induced histopathological damage and oxidative stress in the spleens of pregnant sows and their piglets. The addition of MHNTs to ZEN-contaminated diets can mitigate the negative effects induced by ZEN in the swine.

Catechol metabolites of zeranol and 17ß-estradiol: a comparative in vitro study on the induction of oxidative DNA damage and methylation by catechol-O-methyltransferase.

α-Zearalanol (α-ZAL, zeranol) is a highly estrogenic macrocyclic ß-resorcylic acid lactone, which is used as a growth promotor for cattle in various countries. We have recently reported that α-ZAL and its major metabolite zearalanone (ZAN) are hydroxylated at the aromatic ring by microsomes from human liver in vitro, thereby forming two catechol metabolites each. Thus, the oxidative metabolism of α-ZAL and ZAN resembles that of the endogenous steroidal estrogens 17ß-estradiol (E2) and estrone (E1), which also give rise to two catechols each. As these catechol metabolites are believed to mediate the carcinogenicity of E2 and E1 by causing oxidative DNA damage and DNA adducts, their methylation by catechol-O-methyltransferase (COMT) is an important inactivation pathway. Here we report that hepatic microsomes from five species generate catechol metabolites of α-ZAL and ZAN, the highest amounts being formed by human liver microsomes, followed by rat, mouse, steer and swine. The microsomal extracts and the individual catechols of α-ZAL, ZAN, E2 and E1 were found to induce oxidative DNA damage, as measured by the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in a cell-free system. The ranking of pro-oxidant activity was 15-HO-ZAN>15-HO-α-ZAL≈4-HO-E2/E1≈2-HO-E2/E1>13-HO-ZAN>13-HO-α-ZAL. With respect to the rate of methylation by human hepatic COMT, the ranking was 2-HO-E2/E1>>4-HO-E2/E1>15-HO-α-ZAL/ZAN>>13-HO-α-ZAL/ZAN. Thus, some catechol metabolites of α-ZAL and ZAN are better pro-oxidants and poorer substrates of COMT than the catechols of E2 and E1. These findings warrant further investigations into the genotoxic potential of α-ZAL, which may constitute another biological activity in addition to its well-known estrogenicity.

ZEN and the art of breast health maintenance.

Zearalenone (ZEN) is a non-steroidal mycoestrogen that widely contaminates agricultural products. ZEN and its derivatives share similar molecular mechanisms and activity with estrogens and interact with ERα and ERß leading to changes in the reproductive system in both animals and humans. The reduced form of ZEN, α-ZEA ralenol, has been used as an anabolic agent for animals and also proposed as hormonal replacement therapy in postmenopausal women. Furthermore, both zearelanol ZEN and derivatives have been patented as oral contraceptives. ZEN has been widely used in the United States since 1969 to improve fattening rates in cattle by increasing growth rate and feed conversion efficiency. Evidence of human harm from this practice is provided by observations of central precocious puberty. As a result, this practice has been banned by the European Union. As ZEN has been associated with breast enlargement in humans, it has been included in many bust-enhancing dietary supplements but epidemiological evidence is lacking with regard to breast cancer risk. Extensive work with human breast cancer cell lines has shown estrogenic stimulation in those possessing ER but a reduction in DMBA-induced breast cancers in rodents given ZEN. Protein disulfide isomerase provides a molecular biomarker of dietary exposure to ZEN and its derivatives allowing the detection and control of harmful food intake. The interaction of ZEN with anti-estrogens, anticancer agents and antioxidants requires further investigation.

Alimentação de leitoas pré-púberes com dietas contendo zearalenona / Feeding of pre-pubertal gilts with diets containing zearalenone

O desempenho, o peso de alguns órgãos e a morfologia vulvar de leitoas pré-púberes, alimentadas por 28 dias com dietas contendo zearalenona, foram avaliados. O delineamento experimental utilizado foi inteiramente ao acaso, com dois tratamentos, dieta controle (DC) e dieta controle + 2mg kg-1 de zearalenona (DZ), e seis repetições cada. Não houve diferença (P>0,05) entre os tratamentos para consumo médio diário de ração (1,24 x 1,19kg), ganho médio diário de peso (0,68 x 0,71kg), conversão alimentar (1,86 x 1,71) e peso vivo (PV); (30,9 x 30,4kg). A zearalenona não alterou (P>0,05) os pesos absoluto e relativo do coração (137 x 141g e 0,45 x 0,45 por cento PV), fígado (699 x 699g e 2,31 x 2,26 por centoPV), rins (47 x 49g e 0,15 x 0,16 por centoPV) e baço (166 x 171g e 0,55 x 0,55 por centoPV). Houve aumento (P<0,05) no comprimento (17 x 27cm) e no peso (23 x 157g e 0,07 x 0,51 por centoPV) do trato reprodutivo das leitoas do grupo DZ. O volume vulvar ao final do período foi 820 por cento maior (P<0,05) nos animais alimentados com zearalenona (941 x 8658mm³/kgPV0,6). Os resultados indicam que em suínos a zearalenona e seus metabólitos possuem atividade estrogênica, mas não interferem no desempenho dos animais.

The performance, the weights of some organs, and the vulvae morphology in pre-pubertal gilts fed diets containing zearalenone were evaluated during 28 days. The experimental design was completely randomized with two treatments (control diet, ZD - control diet + 2mg kg-1 of zearalenone) and six replications of each were done. No differences (P>0.05) between treatments for daily feed intake (1.24 x 1.19kg), average daily gain (0.68 x 0.71kg), feed conversion ratio (1.86 x 1.71), and live weight (30.9 x 30.4kg) were observed. Zearalenone did not change (P>0.05) the absolute and relative weights of heart (137 x 141g and 0.45 x 0.45 percentBW), liver (699 x 699g and 2.31 x 2.26 percentBW), kidneys (47 x 49g and 0.15 x 0.16 percentBW), and spleen (166 x 171g and 0.55 x 0.55 percent BW). However, zearalenone increased (P<0.05) the length (17 x 27cm) and weight (23 x 157g and 0.07 x 0.51 percentBW) of the reproductive tract. The final vulvae volume was 820 percent larger (P<0.05) in gilts fed diets containing zearalenone than those fed control diet (941 x 8658mm³/kgBW0.6). Results suggested that zearalenone and its metabolites have an estrogenic activity in pigs without changing the animal performance.

[Nutritional health aspects of mycotoxins]. / Mikotoxinok táplálkozás-egészségügyi vonatkozásai.

Mycotoxins produced by mould fungi can enter into the human food chain directly through foods of plant origin (cereal grains), consumer goods (coffee and bear) and indirectly through foods of animal origin (kidney, liver, milk and eggs). Mycotoxins occur in small amount in the foods; however their continuous intake even in microdoses can result in accumulation in the organism. Synergic effects of the mycotoxins as well as their possible additive multi-toxic effects seem to be especially dangerous. Mycotoxin problems are very important in Hungary because these natural toxins occur mainly in those cereals (e.g. wheat, maize) that amount to high proportion of the sowing area in Hungary and provide the main foods to the inhabitants. Public health risks of the toxins accumulating in the human and animal bodies during the long term consumption of the mycotoxins containing foods--even in small doses--have not been evaluated yet as thoroughly as their importance would require. However, there are more and more direct and indirect expressions of the danger resulting from the toxins. The most frequently observed human health effects are carcinogen effects (aflatoxin, ochratoxin A, fumonisins, patulin); effects causing developmental abnormalities (zearalenon, ochratoxin); effects harmful to the reproduction (zearalenon, and trichotecenes), effects decreasing the resistance; immunosuppressive effects (trichotecenes), and effects causing injury of the nervous system (ochratoxin A, fumonisins). Prevention of the injury of the health caused by mycotoxins can be completed by joint and integrated activity of the various disciplines only and requires a comprehensive interdisciplinary cooperation. This paper gives a discussion on health injuring effects of the most frequently occurring mycotoxins that are very important from human health aspects in Hungary; on their occurrence in the foods and on their human risk.

Prepubertal zearalenone exposure suppresses N-methyl-N-nitrosourea-induced mammary tumorigenesis but causes severe endocrine disruption in female Sprague-Dawley rats.

The effect of prepubertal exposure to zearalenone, an estrogenic mycotoxin, on N-methyl-N-nitrosourea (MNU)-induced mammary tumorigenesis and its influence on reproductive organs were examined in female Sprague-Dawley rats. Prepubertal rats were treated daily with either 0.1 or 10 mg/kg body weight of zearalenone between 15 and 19 days of age and compared with zearalenone-untreated animals (30 rats in each group). Six rats in each group were autopsied at 28 days of age, and their growth was evaluated. All remaining rats were given 50 mg/kg body weight MNU at 28 days of age and followed by monitoring for occurrence of mammary tumors > or =1 cm in diameter. Zearalenone did not affect body weight increase, and mammary glands showed similar development at 28 days of age (time at carcinogen administration). Both low- and high-dose zearalenone treatment significantly reduced incidence of mammary tumors > or =1 cm in diameter but did not influence latency (time between MNU administration and harvest of mammary tumor > or =1 cm in diameter) compared with untreated controls. Zearalenone dose dependently suppressed the number of histologically detected tumors (carcinomas) and multiplicity; the suppression was significant with high-dose treatment. However, high-dose treatment caused significantly earlier vaginal opening, both low- and high-dose treatment significantly caused irregularity of estrous cycle (persistent estrus or prolonged diestrus) at 8 to 10 wk of age, and zearalenone dose dependently increased the number of anovulatory rats (ovaries without newly formed corpora lutea) at 37 wk of age. Thus, short-duration zearalenone treatment in the prepubertal period suppressed subsequent mammary cancer occurrence but also severely damaged ovarian functions. This suggests that ingestion of foods containing zearalenone in the infantile period can have dramatic effects in later life.

Eficiência reprodutiva de porcas intoxicadas por zearalenona em diferentes idades / Reproductive performance of female pigs intoxicated by zearallenone in different ages

Fêmeas suínas foram intoxicadas com zearalenona durante a vida intreuterina, ao desmame (42 dias), ao 150§ dia de idade ou imediatamente após o desmame da primeira leitegada, para se avaliar o comprometimento causado pela zearalenona sobre o desempenho reprodutivo. A intoxicaçäo foi efetuada com raçäo contendo 5ppm de zearalenona, fornecida durante 30 dias. A micotoxina causou retardamento na puberdade e na idade à primeira cobriçäo fértil, nas fêmeas nascidas de porcas intoxicadas durante a gestaçäo. Diferenças de produtividade (P<0,10) entre os grupos, especialmente no número total de leitöes nascidos e no intervalo desmame-cio, foram observadas na primeira, mas näo na segunda leitegada, mostrando a recuperaçäo das fêmeas intoxicadas. Esta recuperaçäo, caracterizou-se pelo desaparecimento dos sintomas entre 3 e 10 dias após a retirada da dieta tóxica e pelo exame histológico do trato genital após o segundo parto, que comprovou ausência de sequelas. Conclui-se que a zearalenona retarda a puberdade de fêmeas intoxicadas durante a vida intrauterina, causa reduçäo do número total de leitöes nascidos e aumenta o intervalo desmama-cio na primeira leitegada, porém com retorno à produtividade normal na segunda leitegada após a intoxicaçäo

[The significance of the mycotoxins desoxynivalenol, zearalenone and ochratoxin A for agricultural domestic animals]. / Uber die Bedeutung der Mykotoxine Desoxynivalenol, Zearalenon und Ochratoxin A für landwirtschaftliche Nutztiere.

Mycotoxins are metabolic products of mycotoxins which have various chemical structures and show various toxic effects. Deoxynivalenol (vomitoxin) is an important economic factor in pig production due to growth depression and suppression of the immune system. Previous studies have shown that the 1-ppm limit in the sole feed for pigs should not be exceeded. Studies of methods of detoxification have as yet not produced conclusive results. Zearalenone has an tolerable effect and may lead to fertility disturbances on the oestrogen production in pigs and can cause remarkable economic damage even in the ppb range. Recommendations of upper limits cannot be made on the basis of the available results. The kidney toxin ochratoxin A is of importance in pig and poultry breeding and--due to its accumulation in the tissue--represents a possible source of danger to man. Since a possible carcinogenic effect of the toxin cannot be excluded, its content in animal rations should be kept as low as possible. For ruminants mycotoxins as a whole do not represent a particular source of danger as these substances can be degraded or converted by rumen flora.

Effect of prepubertal consumption of zearalenone on puberty and subsequent reproduction of gilts.

Forty-eight prepubertal gilts (178.7 +/- 4.1 d; 94.2 +/- 4.1 kg), 16 in each of three trials, were assigned randomly to receive 0 (C) or 10 ppm zearalenone (Z) daily in 2.5 kg of a 14% protein finishing ration for 2 wk. Blood samples were collected at 20-min intervals for 4 h 1 wk after the start of the experiment and 1 wk after Z was withdrawn. Two weeks after Z was withdrawn, gilts were exposed to mature boars 15 min per day for 3 wk. Gilts in estrus were mated to two different boars 12 h apart. Twice each week, blood was sampled and analyzed for progesterone to establish age of puberty. Age at puberty differed (P = .008) among replicates but was similar (P = .13) between Z and C gilts within each replicate. Mean serum concentrations of LH were suppressed (P = .025) during consumption of Z (.25 vs .42 ng/ml) but were similar (P = .16) to concentrations in C gilts 1 wk after Z was withdrawn (.35 vs .45 ng/ml). Frequency and amplitude of LH secretory spikes did not differ (P greater than .50) between Z and C gilts during either sampling period. Mean serum concentrations of FSH were similar (P = .25) between Z and C gilts. Number of corpora lutea and live fetuses were similar (P = .29 and P = .94, respectively) between Z and C gilts. Fetal weights were greater (P = .025) and crown to rump length tended to be greater (P = .10) in fetuses from Z gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Fusarium roseum (Gibberella zea) on pregnancy and the estrous cycle in gilts fed molded corn on days 7-17 post-estrus.

A laboratory produced corn culture of Fusarium roseum (Gibberella zea) was fed as 10% of the total diet to bred and non-bred gilts on days 7-17 postestrus. The corn culture contained both zearalenone and deoxynivalenol by analysis, and caused considerable feed refusal. Although 6 of 10 bred gilts fed the corn culture appeared to be pregnant by ultrasound testing between days 40-50 post-breeding, none of them farrowed. Progesterone analyses indicated that none of the 10 gilts cycled normally during the 20 week observation period. Three maintained high serum progesterone (greater than 10 ng/ml) during the entire period. Progesterone analyses were similar in 5 non-bred gilts fed the corn culture in that none of them cycled normally in 20 weeks. The retention or loss of corpora lutea could not be attributed to levels of luteinizing hormone, as no relationship was found between concentrations of progesterone and luteinizing hormone. This experiment indicates that limited dietary exposure of female swine to Fusarium roseum infected corn can result in embryonic loss and disruption of normal reproductive cycling for an extended length of time.

Should we worry about animal growth promoters?

Estrogens and compounds with estrogenic activity have been used for many years as animal growth promoters and to synchronize estrus in cows. The resorcylic acid lactones (RALS), which include zearalenone, are being used increasingly for these purposes. These estrogenic mycotoxins, now produced commercially, have teratogenic, mutagenic, and carcinogenic properties. There is some evidence that their residues could remain in certain organs at the time the animal products come to market, and this may be of medical significance.

Effect of Fusarium roseum corn culture containing zearalenone on early pregnancy in swine.

A corn culture of Fusarium roseum was added to a standard corn-soybean swine gestation ration. Low, middle, and high dosage mixed feeds contained 7, 38, and 64 mg of zearalenone/kg of feed (7, 38, and 64 ppm) and 0.5, 2.5, and 4.5 mg of deoxynivalenol/kg, respectively. Control feed was the standard ration without added F roseum corn culture. Mature gilts were bred by natural service and fed control or F roseum molded feed from 3 to 34 days after breeding. The main effect of the molded feed was an inhibition of fetal development, with decreased numbers of fetuses present in treated animals at slaughter (38 to 43 days after breeding). Normal litters were present in 7 of 8 control animals, in 2 of 4 gilts given the low-dosage feed, in 1 of 4 gilts given the medium dosage, and in 0 of 4 given the high-dosage feed. Corpora lutea were maintained in all treated animals, as evidenced by serum progesterone concentrations. Serum estradiol concentrations were decreased in gilts in the middle- and high-dosage groups. The genital system of the gilts fed low- and middle-dosage feeds had a gross and microscopic appearance similar to that of the pregnant controls and reflected prolonged progesterone stimulation. Morphologic changes in the genital system of the high-dosage group were intermediate between changes induced by progesterone and those induced by estrogen. Clinical signs of hyperestrogenism and partial feed refusal were noticed in only some of the high-dosage group animals.

Neonatal exposure to zearalenone causes persistent anovulatory estrus in the rat.

The effect of neonatal administration of zearalenone on the female reproductive system was studied in the rat. A single subcutaneous injection of 1.0 mg zearalenone to 3- or 5-day-old rats caused persistent vaginal estrus in adulthood. Ovaries in these animals contained many large follicles but no newly formed corpora lutea. The same effects were observed in rats which had received 100 micrograms estradiol-17 beta in the neonatal period. Most rats which had received 100 micrograms zearalenone or 10 micrograms estradiol-17 beta showed regular 4-day estrous cycles and had newly formed corpora lutea in their ovaries. These results demonstrate that neonatal exposure to zearalenone produced persistent anovulatory estrus in the rat, the potency being about one tenth that of estradiol-17 beta.