Endocrine Disruptors; Known Effects of ZEA At an introductory level, Yang et al (2015) state that endocrine disruptors are chemicals that interfere with the hormone systems and produce adverse developmental, reproductive, neurological, and immunological effects in mammals. Endocrine disruptors can be found in many products including plastic bottles, metal food cans, detergents, flame retardants, food, toys, cosmetics, and pesticides. Endocrine disruptors are chemicals, known as EDC’s, that can interfere with endocrine systems at certain doses. These disruptions can cause cancerous tumours, birth defects, and other developmental disorders. Any system in the body controlled by hormones can be derailed by hormone disruptors. An endocrine disruptor affects hormonal actions in different ways for example they may directly influence hormone biosynthesis, metabolism, transport and mechanism of action on both the receptor and post-receptor levels.

Endocrine Disruptors; Known Effects of ZEA

At an introductory level, Yang et al (2015) state that endocrine disruptors are chemicals that interfere with the hormone systems and produce adverse developmental, reproductive, neurological, and immunological effects in mammals. Endocrine disruptors can be found in many products including plastic bottles, metal food cans, detergents, flame retardants, food, toys, cosmetics, and pesticides.Endocrine disruptors are chemicals, known as EDC’s, that can interfere with endocrine systems at certain doses. These disruptions can cause cancerous tumours, birth defects, and other developmental disorders. Any system in the body controlled by hormones can be derailed by hormone disruptors. An endocrine disruptor affects hormonal actions in different ways for example they may directly influence hormone biosynthesis, metabolism, transport and mechanism of action on both the receptor and post-receptor levels.

Endocrine disruptors are chemicals, known as EDC’s, that can interfere with endocrine systems at certain doses. These disruptions can cause cancerous tumours, birth defects, and other developmental disorders. Any system in the body controlled by hormones can be derailed by hormone disruptors. An endocrine disruptor affects hormonal actions in different ways for example they may directly influence hormone biosynthesis, metabolism, transport and mechanism of action on both the receptor and post-receptor levels. An endocrine disrupting chemical (EDC) represents a large range of agents from natural compounds such as hormones, plants and fungal constituents. Some EDCs act like "hormone mimics" and trick the body into thinking that they are hormones , while some block natural hormones from doing their job. ZEA is a prime example of a hormone mimic. Other EDCs can increase or decrease the levels of hormones in our blood by affecting how they are made, broken down, or stored in our body. And others can change how sensitive our bodies are to different hormones.One such EDC is zearalenone or ZEA, a potent estrogenic metabolite.According to Minervini et al (2001), zearalenone (ZEA) and its derivatives (alpha- zearalenol known as A-ZOL and beta-zearalenol known as B-ZOL, zeranol known as A-ZAL, taleranol known as B-ZAL and finally zearalenone known as ZAN). FIGURE!!!. The precise part of zea being degraded is the c-8 keto group according Olsen et al (1981).These derivatives also play an important part in the endocrine disrupting effect of ZEA in particular zeranol.Utermark and Karlovsky (2007) further state that zearalenone (ZEA) and its derivatives exert estrogenic and anabolic effects on mammals. Carryover of zearalenone from infected grain to feedstuff causes reproductive problems in pigs, sheep, and other farm animals, including precocious sexual development, vulva enlargement, pseudopregnancy, loss of embryos, and reduced litter size.Keller et al (2015) state that zearalenone (ZEA) and its derivatives are mycotoxins with estrogenic effects on mammals. The biotransformation for ZEA in animals involves the formation of two major derivatives , α- and β-zearalenol (α-ZOL and β-ZOL), which are subsequently conjugated with glucuronic acid. For the most part the long lasting known effects of ZEA can be categorised into three main areas; those effects that alter metabolic balance; those effects that contribute to developmental disorders and those effects that negatively impact the reproductive cycle. In fact the greatest effects of ZEA can be found in the reproductive system. ZEA has the ability to cause adverse reproductive effects due to its ability in mimicking the hormone estradiol. Wang et al (2014) declared zearalenone resembles 17beta-estradiol an endogenous estrogen in both its structure and shape which is clearly the prime reason for its estrogenic activity as it activates the estrogen gene to cause the effects. FIGURE (ZEA VS ESTRADIOL)ZEA causes numerous toxic effects in both domestic and laboratory animals, the most common of which relates to the reproductive system. Zearalenone once administered can be most commonly found in the reproductive organs and reproductive system. It is observed in the female reproductive tissue (ovary and uterus) as well as the adipose tissue and interstitial cells of the male reproductive organ: the testes as recently proven by Kuiper-Goodman et al(1987)It effects many animals such as swine, equine & bovine, which we explore below. Swine are the most susceptible species to the reproductive effects of Zearalenone as discovered by many such as Gareis et al (1990) Gajecki et al (2002) Andretta et al(2008)Swine are the most susceptible species to Zearalenone’s endocrine disrupting effects, with prepubertal animals (gilts) the most sensitive. As such it has heavily affected the pork industry. It has been reported (Vanyi et al (1993); Katzenellenbogen and Korach, (1997); Obremski et al (2003); Malekinejad et al, (2007)) that pigs are more sensitive to the reproductive effects of ZEA than other domestic animals. ZEA has an effect on weaned gilts causing vulva hypertrophy and ovarian atrophy. According to Obremski et al (2003), ZEA causes sterility in sows by inciting ovarian disorders where Oocytes die in follicles and therefore ovulation cannot occur. ZEA, very similar to 17 beta-E2 inhibits the secretion of steroid hormones, thus in turn would disrupt oestrogen responses , also suppressing the maturation of ovarian follicle (Katzenellenbogen and Korach, 1997). In a study by Malekinejad et al (2007), gilts were given a diet that contained 3.61 to 4.3 mg/kg ZEA from puberty to mating stages. In about 45% of these gilts, pseudo pregnancies were induced with ZEA. Along with this, ZEA had a suppressing effect on the pig oocyte progression through meiosis by inducing the malformation of meiosis spindles. In their study, Vanyi et al (1993) concluded hyperestrogenismis a common effect of ZEA in porcine, especially new born piglets. Typical clinical signs of this would be swelling of the vulva, increase in uterine size and secretions, mammary gland hyperplasia and secretion and prolonged oestrus due to the estrogenic activity seen to occur on behalf of zea being present. Secondary complications are still births and vaginal and or rectal prolapse indirect effects of the zea activity. Kanora and Maes (2009) observed that pregnant sows and gilts receiving food that is contaminated with ZEA would show smaller litters. This would have a more significant effect if given at early pregnancy as ZEA interferes with the response of the endometrium to progesterone during the embryo implantation. In the equine species there is limited information and experimental evidence to date on the effects of dietary exposure to ZEA on reproduction. Zearalenone is absorbed by the gastrointestinal tract quickly after it is ingested. According to Olsen et al (1987) its effects then occur due to the interaction of the mycotoxin with the enzyme 3 alpha (beta) - hydroxysteroid dehydrogenase, that is responsible for metabolising it into its derivatives.In one of a number of experiments carried out by Minervini et al (2006), they investigated the effect of ZEA in equine species. The study on granulosa cells in vitro, collected from mare ovaries during the breeding season concluded that ZEA could be the reason for reproductive failures according to the cellular disturbance in vitro. Minervini et al (2006) go on to state that it (ZEA) can also effectively stimulate follicular atresia.However, a more recent experiment carried out by Vance et al (2019) would seem to contradict Minervini et al (2006). This experiment involved the splitting of mares into three groups, each of which were administered a certain dose of ZEA which continued for three oestrus cycles. The effects were monitored, and the results collected showed that ZEA does not have much influence on reproduction as it did not cause any reproductive effects. However, Vance et al (2019) qualified this further by stating ‘when consumed in low amounts’. Juhasz et al (2001) supported Vance et al (2019) theory of no effects being witnessed on reproductive parameters in equine species, when they investigated the effect of a low dosage of ZEA. Here they proved that treatment did not affect the duration of follicular phase in mares.Gimeno and Quintavilla (1983) observed that horses suffered from toxicity after being fed corn screenings and this resulted in adverse effects such as oedematous vulvas, prolapsed vaginas oversized uteri and internal haemorrhage on account on their exposure to ZEA that was present in the corn. The effects observed were concluded to be as a result of ZEA mimicking the hormone estradiol as stated previously.In the case of equine we found that there is not sufficient evidence to prove nor eliminate the effects of ZEA on the reproductive cycle in horse so therefore more research must be done to confirm the effects.As is the case with equine, the research & results related to the effects of ZEA on reproduction in the bovine species are very conflicting. There are a few cases that support the fact that Zearalenone does not cause any reproductive effects in the bovine species. In their studies, Weavers et al (1986a) verified that Zearalenone in the bovine species failed to produce any obvious effects on reproduction but did note that the conception rate was decreased by about 25% on account of ZEA’s estrogenic avctivity. They also showed no effect on differential cell counts, clinical signs and sexual behaviour, therefore according to this scientific study, imposing no threat to dairy cow health. Although the above case has proven no significant effects on the reproduction system occurs, Weaver et al (1986b) cited a common problem in that the corpus lutea were smaller in bovine administered with Zearalenone as indicated through rectal palpation. Estradiol has a primitive role in reproduction and sexual function as well as an impact on health of other tissues, the decrease in size of the corpus lutea occurs due to mimicking effect of ZEA .However, in the particular case of dairy cows, more promising and positive results are being proven.Notwithstanding Weavers et al (1986a & 1986b) experiments, the effects of ZEA were seen in a later experiment by Towers et al (1995) where high levels of Zearalenone in the blood seemed to result in low fertility. Towers et al (1995) also discovered symptoms of the ZEA toxicosis that included mammary enlargement of virgin heifers. Coppock et al (1990) carried out an experiment that concluded that diets with about 660 ppb ZEA resulted in poor consumption, depressed milk production, increased reproductive tract infections and total reproductive failure, therefore contradicting the earlier studies of Weaver et al (1986a & 1986b)Having reflected on a number theories regarding the effects of ZEA on the reproductive system in swine, equine and bovine species we have found that in the bovine species (particularly in the case of dairy cows) the effects are more prominent than the equine. However, it was evident that the swine species are still the most dominant species affected by Zearalenone. It is also very clear that the reproductive effects and all the symptoms mentioned above in each species happen on account of ZEA’s ability to impersonate the hormone estradiol therefore proving to be an endocrine disruptor due to its relationship with the endcorines system through the hormone estradiol.