Da Form 5221 R Child Development Services Cds Family Child Care Fcc Certification Denial Revocation Lra
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Da Form 5221 R Child Development Services Cds Family Child Care Fcc Certification Denial Revocation Lra
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Carolyn W.
Lipid Research Center, New Jersey Institute of Food, Nutrition and Health, Rutter University, New Brunswick, NJ 08901, USA
Pdf) The Association Between Exposure To Secondhand Smoke And Psychological Symptoms Among Chinese Children
Received: 29 April 2021 / Revised: 17 May 2021 / Accepted: 18 May 2021 / Published: 24 May 2021
Contamination of the global food supply and animal feed with mycotoxins has become a concern as global temperatures increase and fungi increase. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has been detected at low levels in meat, milk, and spices. A synthetic derivative of ZEN, geranol, is used as a growth promoter in beef production in the United States (US) and Canada. Experimental studies have shown that JN and geranol disrupt the endocrine and reproductive systems, causing infertility, polycystic ovary syndrome-like phenotypes, reduced pregnancy rates, and low birth weight. With extensive human dietary exposure and experimental evidence of endocrine-disrupting properties, a comprehensive review of the effects of ZEN, geranol, and their metabolites on the female reproductive system is warranted. The purpose of this systematic review is to summarize the in vitro, in vivo and epidemiological literature and assess the potential effects of ZEN, geranol and their metabolites (commonly referred to as microestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registry CRD42020166469) of primary reporting items (2000–2020) according to the Guidelines for Systematic Reviews and Meta-Analyses (PRISMA). Data sources from PubMed, Web of Science and Scopus searches are primary English language published literature. The ToxR tool was used for bivariate risk assessment In vitro and in vivo studies (n = 104) were identified and, in general, negative effects of mycoestrogens on physiological processes, organs and tissues related to female reproduction are consistently confirmed. In nonpregnant animals, mycoestrogens alter the follicular profile in the ovary, disrupt estrous cycling, and increase myometrial thickness. In addition, mycoestrogen exposure during pregnancy contributes to placental bleeding, labor, and fetal growth. No epidemiological studies meeting the inclusion criteria were identified
Zeralenone (ZEN) is a secondary metabolite of the Fusarium fungus and one of the leading mycotoxin contaminants in the world’s food supply. ZEN contaminates cereal grains (eg, corn, wheat, barley, oats, and alfalfa) and occurs widely in processed foods (eg, pasta, breakfast cereals, and bread) [1, 2, 3]. Several studies have confirmed ZEN concentrations in food products above the European Union (EU) maximum contamination limit (100–200 µg/kg for processed grains, 75 µg/kg for unprocessed grains) [2]. At the same time, adverse reproductive health outcomes following mycoestrogen exposure were reported in the animal husbandry literature [ 4 , 5 ]. Mycoestrogen exposure in pigs caused valvo-edema, enlarged uterus, sclerotic and atrophic changes in ovaries, and decreased fetal weight. There has been limited research on the potential effects of microestrogens on human health However, with extensive mycoestrogen contamination of the food supply and climate change proving their growth, further research is needed [6, 7, 8].
Its effects on reproductive health endpoints are mediated by ZEN’s ability to modulate estrogen signaling (Figure 1). Its chemical structure is similar to 17β-estradiol (E).
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), allowing direct binding to nuclear estrogen receptors α (ERα) and β (ERβ). Additionally, the ZEN and geranol structures lack the sterol backbone and are therefore not considered steroids. However, in ligand-activated receptor binding assays, the ZEN-ERα complex binds to the estrogen response element (ERE) with similar affinity to E.
ZEN = 70 nM) [10]. Similarly, a Zn metabolite, α-geralenol (α-ZOL), is similar to estrogen, estradiol (EC).
) and 70 times more potent than ZEN as shown in human reporter gene analysis. Other ZEN metabolites can also bind to ERα/β (Figure 2). Thus, ZEN’s ability to bind directly to the estrogen receptor may explain its greater estrogenic potency than other known endocrine disruptors.
> ZEN > genistein > bisphenol A (BPA) > dibutyl phthalate (DBP) > di(2-ethylhexyl) phthalate (DEHP)] [12, 13, 14]. Estrogenic potency of microestrogens has also been demonstrated in vivo For example, ZEN and its metabolites readily bind to cervical ERα and ERβ receptors in mice, rats, and pigs [ 15 , 16 , 17 , 18 ]. Pig studies show that ZERA binds to EREN more strongly than ZEN or its α- and β-ZOL metabolites. The ability of ZEN and its metabolites to bind to estrogen receptors has earned them the name “mycoestrogens”. Although some literature suggests that other mycotoxins may be (i.e., alternative) mycoestrogens for the purposes of this review, we use the term mycoestrogens to refer only to ZEN, geranol, and their metabolites [ 19 , 20 ].
Bulletin Of The University Of Kentucky, Volume 27 (1957 1958)
Because of its ability to influence estrogen effects, microestrogens can disrupt the hypothalamic-pituitary-gonadal (HPG) axis, affecting the development and function of the female reproductive system. The HPG axis regulates gonadal secretion of sex steroids through several positive and negative feedbacks directed at hormone levels. For example, gonadotropin-releasing hormone (GnRH) released by the hypothalamus, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are released by the anterior pituitary. FSH and LH stimulate the ovaries to release estrogen Estrogen creates a negative feedback loop and inhibits GnRH release by the hypothalamus. During folliculogenesis, oocytes grow and develop into granulosa cells, which function to secrete sex steroids (ie E).
) supports HPG axis function including oocyte growth and development Animal studies have shown that ZEN affects ovarian follicle development and function, resulting in a significant reduction in E proliferation.
Levels directly affect growth, but can also alter LH and FSH concentrations, with the direction of change (ie, enhancement or suppression) depending on the model organism, exposure time, and dose [ 21 , 25 , 26 , 27 , 28 ]. This discrepancy in response may result from significant cross-sectional variation in the biotransformation of ZEN and geranol. This may also explain why α-ZAL, the synthetic form of geranol, is marketed as a growth promoter in the US and Canadian livestock industry, while experimental animal models show reduced effects after pregnancy [ 22 , 29 ].
The main route of human exposure to ZEN is through the diet, and biotransformation in mammals has been well characterized. In pigs, 30-50% of an oral dose (10 mg/kg bw) is absorbed and has a half-life of 86 hours [30], but absorption and half-life may be shorter in other species. Studies in several animal models have shown that after ingestion, ZEN is distributed mainly to the liver (pig, sheep, cow, mouse, rat, and chicken), but also to the reproductive organs (mouse, rat, pig) and placenta. | rabbits, mice) and humans) [32, 33, 34, 35, 36, 37]. Recently, Rogoska et al Briefly, 3α- and 3β-hydroxysteroid dehydrogenase (HSD) in the liver converts ZEN to α-ZOL, β-ZOL and zearalanone (ZAN). In pigs, the first phase metabolite is α-ZOL, and in horses and bulls β-ZOL predominates [39]. Further degradation produces α-ZAL (geranol) and β-ZAL, which can degrade to ZAN Phase II metabolism of ZEN or ZEN by UDP-glucuronosyl transferases (UGTs) and sulfotransferases (SULTs) produces glucuronide and sulfate conjugates, which are excreted in bile or urine, respectively. Initial studies in human volunteers performed single administration
Mercer Island Reporter, April 16, 2014 By Sound Publishing
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