Effects of Endocrine Disruptors on Reproductive and Developmental Toxicity

Öz

Studies on endocrine disrupting substances that disrupt the function of the endocrine system, which is the center of the physiological and biological functions of the body, and cause adverse effects on the organism or on the next generations of this organism, have become a subject of interest in recent years. Studies on animal models and humans reveal that the mechanisms by which endocrine disruptors act involve different pathways. Endocrine disruptors; Pesticides, metals, plastic bottles, food packaging, detergents, cosmetic products and many materials used in daily life are natural or synthetic. There is a lot of evidence in the literature that these substances, which mimic the function of endogenous hormones, increase, decrease or block hormone production by manipulating cellular activity, affect many basic biological functions such as the nervous system, neurobehavior, immune and metabolic activity. In addition, endocrine disruptors have been reported to have negative effects on infertility, pregnancy, fetal development and female reproductive health. In this study, the effects and effects of endocrine disruptors such as bisphenol-A (BPA), polychlorinated biphenyls (PCB), diethylstilbestrol (DES), dichlorodiphenyltrichloroethane (DDT), phthalates, metals, ethanol and thalidomide, which are commonly associated with reproductive and developmental toxicity, It was aimed to review the mechanisms of these substances and it was determined that exposure to these substances has the potential to cause toxic damage even between generations in the long term

Anahtar Kelimeler

• Reproductive toxicity
• Developmental toxicity
• Endocrine disruptors

Endokrin Bozucuların Üreme ve Gelişim Toksisitesi Üzerine Etkileri

Öz

Vücudun fizyolojik ve biyolojik işlevlerinin merkezi olan endokrin sistemin, işlevini bozan ve organizmada ya da bu organizmanın gelecek kuşaklarında olumsuz etkilere neden olan endokrin bozucu maddeler ile ilgili çalışmalar son yıllarda oldukça merak konusu haline gelmiştir. Hayvan modelleri ve insanlar üzerine yapılan araştırmalar, endokrin bozucuların etki ettiği mekanizmaların farklı yollar içerdiğini ortaya koymaktadır. Endokrin bozucular; pestisitler, metaller, plastik şişeler, gıda ambalajları, deterjanlar, kozmetik ürünleri ve günlük hayatta kullanılan birçok materyalin içeriğinde doğal veya sentetik olarak yer almaktadır. Endojen hormonların fonksiyonunu taklit eden, hücresel aktiviteyi manipüle ederek hormon üretimini attıran, azaltan veya bloke edebilen bu maddelerin sinir sistemi, nörodavranış, bağışıklık ve metabolik aktivite gibi birçok temel biyolojik fonksiyona etki ettiğine dair literatürde birçok kanıt bulunmaktadır. Bunun yanı sıra endokrin bozucuların infertilite, hamilelik, fetal gelişim ve kadın üreme sağlığı üzerinde de olumsuz etkilere sahip olduğu bildirilmiştir. Bu çalışmada yaygın olarak üreme ve gelişim toksisitesi ile ilişkilendirilen bisfenol-A (BPA), poliklorlu bifeniller (PCB), dietilstilbestrol (DES), pestisitlerin bir türevi olan diklorodifeniltrikloroetan (DDT), fitalatlar, metaller, etanol ve talidomid gibi endokrin bozucuların etkilerinin ve etki mekanizmalarının gözden geçirilmesi amaçlanmış ve bu maddelere maruziyetin uzun vadede kuşaklar arasında bile bir toksik hasar oluşturma potansiyeline sahip olduğu saptanmıştır.

Anahtar Kelimeler

• Üreme toksisitesi
• Gelişim toksisitesi
• Endokrin bozucular

Kaynakça

1. 1. Şirin, B., Ersoy, S., Pala, E. (2019). Suriyeli geçici sığınmacılar ve Türkiye Cumhuriyeti vatandaşlarının gebelik ve doğum sonuçlarının karşılaştırılması: 3. basamak bir hastanede yapılmış vaka kontrol çalışması. Smyrna Tıp Dergisi, 25-32.
2. 2. Bjorvang, R. D., Damdimopoulou, P. (2020). Persistent environmental endocrine-disrupting chemicals in ovarian follicular fluid and in vitro fertilization treatment outcome in women. Upsala J. Med. Sci, 125(2), 85-94.
3. 3. Rolfo, A., Nuzzo A. M., De Amicis, R., Moretti, L., Bertoli, S., Leone, A. (2020). Fetal–maternal exposure to endocrine disruptors: correlation with diet ıntake and pregnancy outcomes. Nutrients, 12(6), 8-19.
4. 4. Tang, Z. R., Xu, X. L., Deng, S. L., Lian, Z. X., Yu, K. (2020). Oestrogenic endocrine disruptors in the placenta and the fetus. Int. J. Mol. Sci, 21(4), 2-16.
5. 5. Monneret, C. (2017). What is an endocrine disruptor? C. R. Biol, 340(2017), 403–405.
6. 6. Bergman, A., Heindel, J. J., Jobling, S., Kidd, K. A., Zoeller, T. (2012). State of the science of endocrine disrupting chemicals. WHO Library.
7. 7. WHO/UNEP. State of the Science of Endocrine Disrupting Chemicals-2012; World Health Organisation: Geneva, Switzerland, 2013.
8. 8. Toppari, J., Virtanen, H. E., Main, K. M., Skakkebaek, N. E. (2010). Cryptorchidism and hypospadias as a sign of testicular dysgenesis syndrome (TDS): Environmental connection. Birth Defects Res. A Clin. Mol. Teratol, 88, 910–919.

9. 9. Diamanti-Kandarakis, E., Bourguignon, J. P., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., et al. (2009). Endocrine-disrupting chemicals: An endocrine society scientific statement. Endocr Rev, 30(4), 293–342.
10. 10. Lucaccioni, L., Trevisani, V., Marrozzini, L., Bertoncelli, N., Predieri, B., Lugli, L., et al. (2020). Endocrine-disrupting chemicals and their effects during female puberty: A review of current evidence. Int J Mol Sci, 21(6), 3-12.
11. 11. Duursen, M., Boberg, J., Christiansen, S., Connolly, L., Damdimopoulou, P., Filis, P., et al. (2020). Safeguarding female reproductive health against endocrine disrupting chemicals-the FREIA project. Int. J. Mol. Sci, 21 9), 2-13.
12. 12. Vandenberg, L. N., Hauser, R., Marcus, M., Olea, N., Welshons, W. V. (2007). Human exposure to bisphenol A (BPA). Reprod Toxicol, 24(2), 139-177.
13. 13. Dodds, E. C., Lawson, W. (1936). Synthetic estrogenic agents without the phenanthrene nucleus (Letter). Nature, 137(3476), 996.
14. 14. Krishnan, A. V., Stathis, P., Permuth, S. F., Tokes, L., Feldman, D. (1993). Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology, 132(6), 2279- 2286.
15. 15. Le, H. H., Carlson, E. M., Chua, J. P., Belcher, S. M. (2008). Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicol Lett, 176(2), 149-156.
16. 16. Calafat, M., Kuklenyik, Z., Reidy, J. A., Caudill, S. P., Ekong, J., Needham, L. L. (2005). Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect, 113(4), 391-395.
17. 17. Welshons, W. V. (2007). Human exposure to bisphenol A (BPA). Reprod Toxicol, 24(2), 139-177.
18. 18. Bouskine, M., Nebout, F., Brucker-Davis, M., Benahmed, P. (2009). Low doses of bisphenol A promote human seminoma cell proliferation by activating PKA and PKG via a membrane G-protein- coupled estrogen receptor. Environ Health Perspect, 117(7), 1053-1058.
19. 19. Ikezuki, Y., Tsutsumi, O., Takai, Y., Kamei, Y., Taketani, Y. (2002). Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod, 17(11), 2839-2841.
20. 20. Brieno-Enriquez, M. A., Reig-Viader, R., Cabero, L., et al. (2012). Gene expression is altered after bisphenol A exposure in human fetal oocytes in vitro. Mol Hum Reprod, 18(4), 171–183.
21. 21. Trapphoff, T., Heiligentag, M., El Hajj, N., Haaf, T., Eichenlaub-Ritter, U. (2013). Chronic exposure to a low concentration of bisphenolA during follicle culture affects the epigenetic status of germinal vesicles and metaphase II oocytes. Fertil Steril, 100(6), 1758–1767.
22. 22. Ehrlich, S., Williams, P. L., Missmer, S. A., et al. (2012). Urinary bisphenol A concentrations and implantation failure among women undergoing in vitro fertilization. Environ Health Perspect, 120(7), 978–983.
23. 23. Ziv-Gal, A., Wang, W., Zhou, C., Flaws, J. A. (2015). The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice. Toxicol Appl Pharmacol, 284, 354–362.
24. 24. Wetherill, Y. B., Akingbemi, B. T., Kanno, J., McLachlan, J. A., Nadal, A., Sonnenschein, C., et al. (2007). In vitro molecular mechanisms of bisphenol A action. Reprod Toxicol, 24(2), 178-198.
25. 25. Markey, M., Luque, E. H., Munoz De Toro, M., Sonnenschein, C., Soto, A. M. (2001). In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod, 65(4), 1215-1223.
26. 26. Munoz De Toro, M., Markey, C. M., Wadia, P. R., Luque, E. H., Rubin, B. S., Sonnenschein, C., et al. (2005). Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology, 146(9), 4138-4147.
27. 27. Maffini, M. V., Rubin, B. S., Sonnenschein, C., Soto, A. M. (2006). Endocrine disruptors and reproductive health: the case of bisphenol-A. Mol Cell Endocrinol, 254, 179-186.
28. 28. Cantonwine, D., Meeker, J. D., Hu, H. Sánchez, B. N., Lamadrid-Figueroa, H., Mercado-García, A., et al. (2010). Bisphenol A exposure in Mexico City and risk of prematurity: a pilot nested case control study. Environ Health, 9(1),1-7.
29. 29. McLachlan, R., Anawalt, B. (2017). Endocrinology of male reproduction. (Erişim tarihi: 28.06.2021).
30. 30. Sutherland, V. (2020). Introduction to reproductive and developmental toxicology. Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States. 207-220.
31. 31. Rebar, R., McGee, E. A. (2017). Endocrinology of female reproduction. (Erişim tarihi: 28.06.2021).
32. 32. Tewari, N., Kalkunte, S., Murray, D. W., Sharma, S. (2009). The water channel aquaporin 1 is a novel molecular target of polychlorinated biphenyls for in utero anomalies. J Biol Chem, 284(22), 15224- 15232.
33. 33. Smith, K. W., Souter, I., Dimitriadis, I., et al. (2013). Urinary paraben concentrations and ovarian aging among women from a fertility center. Environ Health Perspect, 121(11-12), 1299–1305.
34. 34. Conlon, J. L. (2017). Diethylstilbestrol: Potential health risks for women exposed in utero and their o_spring. JAAPA, 30(2), 49–52.
35. 35. Titus, L., Hatch, E. E., Drake, K. M., Parker, S. E., Hyer, M., Palmer, J. R., et al. (2019). Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): a report from the US national cancer institute DES third generation study. Reprod. Toxicol, 84, 32–38.
36. 36. Stroheker, T., Cabaton, N., Nourdin, G., Regnier, J. F., Lhuguenot, J. C., Chagnon, M. C. (2005). Evaluation of antiandrogenic activity of di- (2-ethylhexyl) phthalate. Toxicology, 208(1), 115-21.
37. 37. Kleymenova, E., Swanson, C., Boekelheide, K., Gaido, K. W. (2005). Exposure in utero to di (n-butyl) phthalate alters the vimentin cytoskeleton of fetal rat Sertoli cells and disrupts Sertoli cell- gonocyte contact. Biol Reprod, 73(3), 482-90.
38. 38. Boekelheide, K., Kleymenova, E., Liu, K., Swanson, C., Gaido, K. W. (2009). Dose-dependent effects on cell proliferation, seminiferous tubules, and male germ cells in the fetal rat testis following exposure to di (n-butyl) phthalate. Microsc Res Tech, 72(8), 629-638.
39. 39. Chang, C. C., Hsieh, Y. Y., Hsu, K. H., Tsai, H. D., Lin, W. H., Lin, C. S. (2010). Deleterious effects of arsenic, benomyl and carbendazim on human endometrial cell proliferation in vitro. Taiwan J Obstet Gynecol, 49(4), 449–454.
40. 40. Peretz, J., Gupta, R. K., Singh, J., Hernández-Ochoa, I., Flaws, J. A. (2011). Bisphenol A impairs follicle growth, inhibits steroidogenesis, and downregulates rate-limiting enzymes in the estradiol biosynthesis pathway. Toxicol Sci, 119(1), 209–217.
41. 41. Badr, F. M., El-Habit, O. (2018). Heavy metal toxicity affecting fertility and reproduction of males. In: Suresh Sikka S, Hellstrom W, editors. Bioenvironmental issues affecting men’s reproductive and sexual health. 293-304.
42. 42. Rzymski, P., Tomczyk, K., Rzymski, P., Poniedziałek, B., Opala, T., Wilczak, M. (2015). Impact of heavy metals on the female reproductive system. Ann Agric Environ Med, 22(2), 259-264.
43. 43. Gude, D. (2012). Alcohol and fertility. J Hum Reprod Sci, 5(2), 226-228.
44. 44. Goldberg, J. M., Falcone, T. (1999). Effect of diethylstilbestrol on reproductive function. Fertil Steril, 72(1), 1-7.
45. 45. Mellin, G. W., Katzenstein, M. (1962). The saga of thalidomide: neuropathy to embryopathy, with case reports of congenital anomalies. N Engl J Med, 267, 1184-1192