الفهرس 
ENDOCRINE DISRUPTORSOnly 14 pages are availabe for public view
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Abstract
Endocrine disruptors (EDs) or xenobiotics are natural and synthetic environmental agents that influence the complex and interdependent function of endocrine systems, particularly reproductive system in human and wildlife.
Phytoestrogens are a group of biologically active plant substances with chemical structure similar to that of estradiol as they bind to estrogen receptors and exert various estrogenic and antiestrogenic effects. There are three main classes of phytoestrogens: isoflavons, coumestans and lignans which occur in either plants or theirs seeds. Soya beans are the most abundant source of isoflavons.
Synthetic endocrine disruptors include industrial and pharmaceutical chemicals. Several industrial chemicals are considered as estrogen agonists or antagonists (Wolf et al., 1995). These include: Organochlorine pesticides, pentachlorphenol (PCP), polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), alkylphenols (AP), bisphenols, phthalates and lead.
Pharmaceutical endocrine disruptors include: vinclozolin and prochloraze. Vinclozolin is a systemic dicarboximide fungicide that is used for fruits and vegetable. It acts as androgen receptor agonist. Transient exposure to vinclozoline during the time of testis differentiation alter testis development and function.
Prochloraze is an imidazole fungicide that is widely used in Europe in gardening and agriculture.It acts throught multiple mechanisms, as it antagonizes the androgen and the estrogen receptors, agonizes the (AH) receptors and inhibits aromatse activity. Prenatal exposure to prochloraze feminizes the male offspring due to its action as antiandrogen.
Routes of exposure to endocrinal disruptors include: direct exposure by environmental contact, dietary intake, occupational exposure and exposure in the home by inhalation of aerosol kitchen cleaners containing estrogenic nonionic detergents. The severity of any adverse effects from exposure to endocrinal disruptors depends on the dose, route of exposure, rate of absorption, the effects of its metabolites and its accumulation and persistence in the body. Toxic effects also depend on the health status of the individual. Malnutrition and dehydration are likely to increase sensitivity to endocrine disruptors .
Adverse or therapeutic effects of endocrine disruptors can arise from either primary (direct) or secondary (indirect) effects on endocrine function. Direct acting endocrine disruptors affect the endocrine organ first, resulting in secondary toxicity in other organ systems. On the contrary, indirect acting endocrine disruptors affect some target organs first, influencing the endocrine system to cause indirect effects on other organ systems secondarily.
The reproductive system, however may be sensitive to toxic effects of these compounds than other organ systems. Effects of those compound could occur as a consequence of altered hormone concentration (hormone synthesis or break-down, storage and release, transport and clearance), interaction with the hormone receptor (binding and dissociation kinetics and agonist versus antagonist effects), receptor concentration and hormone-receptor complex interactions with DNA.
Numerous studies demonstrate the interaction of environmental toxicants with steroid receptors and thereby causing interference with developmental and functional aspects of testis, epididymis and accessory sex organs. In recent years, studies of male reproduction health have revealed adverse trends in several western countries including an increased prevalence of hypospadias, cryptochidism and testicular cancer.
The aetiology of TDs syndrome is related to genetic and or environmental factors, including endocrine disruptors.
Reproductive toxins exert their adverse effects on pretesticular, testicular or post-testicular sites. The hypothalmo-hypophyseal-testicular axis may be affected as well as the pulsatile secretion of gonadotrophin-releasing hormone and / or gonadotrophins.
Toxins may impair spermatogenesis directly or indirectly. The blood testicular barrier regulates the passage of molecules but doesn’t protect spermatogonia leading to its direct impairment through cytotoxic or genotoxic effects. Permanent damage of the germinal epithelium is commonly found in case of intense or prolonged damaging conditions.
Alteration in leydig cells functions, the blood testis barrier and the testicular vascular system as well as reactions of the local immune system may be considered as indirect effect of endocrine disruptors resulting in a reduced infertility.
The most important male reproductive toxicants include alkylphenols, bisphenol A, phthalates and chlorinated hydrocarbons.
Toxic effects on reproduction are mainly investigated in animal models. However, it is difficult to transfer these results to the human situation.
Neonatal rats exposed to 8 mg/kg/day of nonyle phenol by intraperitoneal injection showed decreased weights of the reproductive organ and delayed testis descent. In another study the toxicity of (NP) on testis and epididymis in male rats exposed after gestation and early postnantal life was also supported.
In rats, bisphenol A exposure of 2.4µ /Kg / day from postnatal day 21-35 suppresses serum LH, testosterone and estrogen levels. Perinatal exposure to bisphenol A leads to decreased testosterone level in the interstitial fluid in adulthood.
Sertoli and leydig cells are targets for diethyl hexyl phthalate (DEHP) and mono ethyl hexyl phthalate (MEHP). Rodent pubs exposed via diet to DEHP in utero showed vacuolization of sertoli cells and atrophy of the seminiferous tubules. Low dose exposure to DEHP during postnatal life up to adulthood induced high serum levels of LH, testosterone and 17B estradiol. Persistent increase of LH and testosterone increase the risk of the precocious puberty and testicular tumours.
Exposure to lindane during lactation reduced testicular weights and the number of spermatozoa and spermatides at adulthood in male rat offspring.
Several authors reported on significantly decreased sperm count in relation to an elevated PCB metabolite level within a subgroup of men normal semen quality. Another author detected PCBs in the seminal fluid of infertile men.