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Endocrine-Disrupting Chemicals and Male Reproductive Health: a Review

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Endocrine-Disrupting Chemicals and Male Reproductive Health: a Review Strokovni članek Endocrine-disrupting chemicals and male reproductive health: a review Kemični povzročitelji endokrinih motenj in reproduktivno zdravje pri moških: pregled literature Damjan Balabanič,1 Aleksandra Krivograd Klemenčič2 Abstract 1 Faculty of Industrial Balanced functioning of the endocrine system is essential for preservation of human species by Engineering Novo mesto, providing normal growth and development, reproduction, and normal functioning of all other Novo mesto, Slovenia organ systems. In the last decades, emerging area of interest is the impact of environmental 2 Institute for Sanitary exposures to human health. Important environmental pollutants are endocrine-disrupting che- Engineering, Faculty micals (EDCs), which can have adverse effects on the living organism due to their interference of Civil and Geodetic with the endocrine system. The group of known EDCs embraces ubiquitous synthetic substan- Engineering, University of ljubljana, ljubljana, ces used as industrial lubricants and solvents, with their by-products, incomplete combustion Slovenia remains, pharmaceuticals and personal care products, pesticides and plasticizers. Natural com- pounds such as genistein, a phytoestrogen, and heavy metals can also have endocrine effects. Korespondenca/ Correspondence: Endocrine disruption is a serious public health problem. EDCs among other health problems ge- Damjan Balabanič, nerate reproductive disorders in males, such as decreases in sperm count and quality, increases e: damjan.balabanic@ in testicular germ cell numbers, prostate and breast cancers, cryptorchidism and hypospadias, gmail.com impaired fertility, and infertility. This paper critically reviews the current knowledge of the impa- Ključne besede: ct of EDCs on reproductive disorders in human males. kemični povzročitelji endokrinih motenj; endogeni hormoni; okolje; Izvleček reproduktivno zdravje pri Uravnoteženo delovanje hormonskega sistema zagotavlja rast in razvoj, razmnoževanje in nor- moških malno delovanje vseh drugih organskih sistemov v telesu. Zato je ključnega pomena za ohrani- Key words: tev človeške vrste. V zadnjih desetletjih narašča število raziskav, povezanih z izpostavljenostjo endocrine-disrupting ljudi različnim kemičnim snovem iz okolja in njihovim vplivom na zdravje. Kemični povzročitelji chemicals; endogenous endokrinih motenj (KPEM) sodijo med pomembna okoljska onesnažila z negativnim učinkom na hormones; environment; organizem zaradi poseganja v endokrini sistem. V skupino znanih KPEM sodijo povsod prisotne human male reproductive health sintezne snovi, ki se uporabljajo kot industrijska maziva in topila ter njihovi stranski produkti, os- tanki nepopolnega zgorevanja, zdravilne učinkovine, izdelki za osebno nego, pesticidi, mehčala Prispelo: 20. 11. 2016 in drugo. Naravne spojine, kot so genistein, fitoestrogenske snovi in težke kovine lahko prav tako Sprejeto: 18. 12. 2017 moteče delujejo na endokrini sistem ljudi in živali. Motnje endokrinega sistema so resen pro- blem javnega zdravja. KPEM med drugim povzročajo reproduktivne motnje pri moških, kot so zmanjšano število speremskih celic in njihovo nižjo kakovost, rak prostate in dojk, kriptorhizem in hipospadijo, zmanjšano plodnost in neplodnost. V prispevku je predstavljen kritičen pregled trenutnega znanja o vplivih KPHM na reproduktivne motnje pri moških. Citirajte kot/Cite as: Balabanič D, krivograd klemenčič a. endocrine-disrupting chemicals and male reproductive health: a review. Zdrav vestn. 2018;87(1–2):69–80. DOI: 10.6016/Zdravvestn.2456 Endocrine-disrupting chemicals and male reproductive health 69 reproDukcija človeka 1. Introduction In the last decades, numerous stu- high degree of lipophilicity (9) and thus dies have reported that certain chemi- bioaccumulation. Human exposure to cals called endocrine-disrupting che- EDCs may result from the ingestion of micals (EDCs) may cause disruption contaminated food and water, inhala- of the endocrine system and can affect tion of air and absorption of the EDCs reproduction and development of through the skin. However, in most ca- exposed humans and wildlife (1-5). An ses, human exposure to EDCs is through “Endocrine-disrupting chemical” (EDC) the ingestion of contaminated food. The has been broadly defined as “an exoge- EDCs that are most commonly present nous substance or a mixture that alters in contaminated food are bisphenol A function(s) of the endocrine system (BPA), nonylphenol, phthalates, and he- and consequently causes adverse health avy metals. BPA is used as a source ma- effects in an intact organism, or its pro- terial for the production of epoxy resins, geny, or (sub)populations” (6). EDCs can polyacrylates and polyesters, but mainly disrupt the normal actions of endogeno- for the production of epoxy resins and us hormones by altering normal hormo- polycarbonate plastics (10). Epoxy resins ne levels, inhibiting or stimulating the are used as food contact surface lacqu- production of hormones, or changing er coatings for cans, protective coatings the way hormones travel through the and finishes, adhesives and as coatings body, thus affecting the functions that for polyvinyl chloride (PVC) pipes (10). these hormones control (4). Polycarbonate plastics are used in the The group of known EDCs is extre- manufacture of household appliances, mely heterogeneous and includes diffe- food packaging and plastic bottles beca- rent groups of chemicals such as steroids use they have high impact strength, har- (ethinyl estradiol, 17β-estradiol, estrone, dness, toughness, transparency, and re- mestranol and diethylstilbenstrol), al- sistance to temperatures, many acids and kylphenols (nonylphenol, nonylphenol oils (10). In food packaging, nonylphenol ethoxylate, octylphenol and octylphe- originates from oxidation of the antioxi- nol ethoxylate), polyaromatic com- dant additive trisnonylphenyl phosphi- pounds (polychlorinated biphenyls te (11). Levels of nonylphenol in different (PCBs), polycyclic aromatic hydrocar- packaging materials were recently asses- bons (PAHs) and brominated flame re- sed and were found to range from below tardants), organic oxygen compounds 0.03 µg/g in a polyethylene terephtha- (bisphenol A (BPA) and phthalates), late (PET) water bottle to 287 µg/g in pesticides (atrazine, chlordane, deme- PVC cling film (12). Nonylphenol was ton-S-methyl, dichlorvos, dieldrin, di- also detected in different types of reta- methoate, endosulfan, hexachlorobenze- il-purchased foods: up to 78 ng/L were ne, lindane, linuron, pentachlorophenol, found in PET-bottled mineral water (13), permethrin, simazine and trifluralin) and up to 40 µg/kg in beverage cartons of others (tributyltin, dioxins and furans) ultra-high temperatures (UHT) whole as well as certain heavy metals (arsenic, milk and up to 32.3 µg/kg in high density cadmium, lead and mercury) (4,7,8). The polyethylene (HDPE)-bottled milk (in logKow (octanol/water partition coeffi- bottle sterilization) (14). Dimethyl pht- cient) values for some EDCs indicate a halate, Diethyl phthalate, Diisobutyl pht- 70 Zdrav vestn | januar – februar 2018 | Letnik 87 Strokovni članek halate, Di-n-butyl phthalate, Benzylbutyl reproductive health, EDCs have been phthalate, Di(2-ethylhexyl) phthala- linked to disrupted reproductive functi- te, Dicyclohexyl phthalate, Di-n-octyl on (such as reduced semen quality and phthalate, Diisononyl phthalate and infertility), altered fetal development Diisodecyl phthalate were detect in di- (such as urogenital tract abnormalities, fferent fruits and vegetables, sport drin- including hypospadias and cryptorchi- ks, artificial juice drinks, meat and meat dism) and testicular germ-cell, prostate products, fish and fish products, milk and breast cancers (4,5,23). As previou- and nutracevtical products (15,16). Lead sly mentioned, the potential lag between (Pb) in food originates mainly from at- exposure to EDCs and the manifestation mospheric deposition and adherence of of a clinical reproductive disorder is of Pb-rich soil particles to fruits and vege- critical concern. In humans, this period tables (17). Exposure to excess Arsenic may be years or decades post exposure (As), principally from contaminated because sexual maturity and fertility drinking water, is considered one of the cannot be assessed until the exposed in- top environmental health threats worl- dividual has attained a certain age (24). dwide (18). Most of this exposure is from In 1993, Sharpe and Skakkebaek (25) sug- natural geological sources of As that gested fetal exposure to environmental contaminate groundwater (18). It has oestrogens such as synthetic oestrogens, been established that fish and seafood phytoestrogens, oestrogens in milk and can accumulate organic As from their oestrogenic chemicals (e.g. chlorinated environment (19,20). The concentrations hydrocarbon (TCDD)) to be the com- of As in fruits and vegetables depends mon aetiological factor for the observed on the soil content, water contaminati- rise in the incidence of testicular can- on, air pollution and the usage of fertili- cer, cryptorchidism and the downward zers (19). The general human population trend in sperm quality (25). Skakkebaek is exposed to mercury (Hg) (usually in et al. (26) have suggested that the inci- an inorganic form and at very low con- dences of cryptorchidism, hypospadias centrations) primarily through the diet and poor semen quality are risk factors with contaminated fish, dental amalgam for one another and that they are all and water consumption (4,21). The level predictive
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