Is There the Role of Endocrine Disruptors in Autism Spectrum Disorder?

Abstract

The maintenance of human health and generation depends on the perfect functioning of hormones and similar signal carrier substances, which are vital for metabolism, growth-development, mental functions, immune system and reproduction. Babies and young children are more sensitive to contaminants in food than adults. Exposure to endocrine disruptors in infancy and early childhood is important for the development of childhood diseases. In prenatal period, babies may be exposed to contaminants through the placenta. As a result of this exposure, the endocrine system of the body is affected and adverse effects on the neurological, reproductive, cardiovascular, metabolic and immune system occur. Endocrine disruptors can affect thereby changing the effects of estrogen, androgens and thyroid hormones. Autism spectrum disorder (ASD) is a condition that affects both the individual with the disorder and his or her entire family, which has a life-long and often destructive effect. The factors that cause ASD are not definitively known, but there are findings that it is genetic based. Environmental factors may also lead to ASD. A large number of research has been carried out on the effects of both genetic and environmental factors. In recent studies, pregnant women's body fluids (urine, serum) endocrine disruptive substance content and the prenatal body load of chemicals measured and the effects of these on children and their relationship to ASD are examined. Although there are studies on the relationship of endocrine disruptors with ASD, more studies are needed on this subject. In this review, it was aimed to evaluate the possible relationship between OSB and endocrine disruptors according to current study results.

Keywords

• Endocrine disruptors,autism spectrum disruptors,endogenous hormone

Otizm Spektrum Bozukluğunda Endokrin Bozucuların Rolü Var mıdır?

Abstract

İnsan sağlığı ve neslinin devamı metabolizma, büyüme-gelişme, zihinsel işlevler, bağışıklık sistemi ve üreme için yaşamsal rolü bulunan hormon ve benzeri sinyal taşıyıcı maddelerin kusursuz çalışmasına bağlıdır. Bebekler ve küçük çocuklar yetişkinlere oranla besinlerdeki kirleticilere daha duyarlıdır. Bebeklik ve erken çocukluk döneminde endokrin bozuculara maruz kalmak, çocukluk çağı hastalıklarının gelişimi açısından önemlidir. Prenatal dönemde bebekler plasenta yoluyla kirleticilere maruz kalabilirler. Bu maruziyet sonucunda,  vücudun endokrin sistemi etkilenip, nörolojik, üreme, kardiyovasküler, metabolik ve bağışıklık sistemi üzerine olumsuz etkiler ortaya çıkmaktadır. Endokrin bozucular östrojen, androjenler ve tiroid hormonlarının etkisini değiştirerek etki gösterebilir. Otizm spektrum bozukluğu (OSB) yaşam boyu devam eden ve genellikle tahrip edici etkisi olan, hem bu hastalığa sahip bireyi hem de tüm ailesini önemli düzeyde etkileyen bir durumdur. OSB’ye neden olan faktörler kesin olarak bilinmemekle birlikte genetik temelli olduğu bildirilmiştir. Çevresel faktörlerin de OSB’ye neden olabileceği düşünülmektedir. Hem genetik faktörlerin hem de çevresel faktörlerin etkileri üzerine çok sayıda araştırma yapılmaktadır. Son dönemde yapılan çalışmalarda, gebe kadınların vücut sıvılarının (idrar, serum) endokrin bozucu madde içerikleri ile ölçülen kimyasalların prenatal vücut yüküne ve bunların çocuklara olan etkisi ve OSB ile ilişkisine bakılmaktadır. Endokrin bozucuların OSB ile ilişkisi üzerine çalışmalar olmasına rağmen bu konuda daha fazla çalışmaya gerek duyulmaktadır. Bu derleme yazıda OSB ve endokrin bozucular arasındaki olası ilişkinin güncel çalışma sonuçlarına göre değerlendirilmesi amaçlanmıştır.

Keywords

• Endokrin bozucular,otizm spektrum bozukluğu,endojen hormonlar

References

1. Alabdali, A., Al-Ayadhi, L., & El-Ansary, A. (2014). A key role for an impaired detoxification mechanism in the etiology and severity of autism spectrum disorders. Behavioral and Brain Functions, 10(1), 14.
2. Association, D.-A. P. (2013). Diagnostic and statistical manual of mental disorders. Arlington: American Psychiatric Publishing.
3. Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (2009). Autism as a strongly genetic disorder: evidence from a British twin study. Psychological Medicine, 25(01), 63. doi:10.1017/s0033291700028099
4. Baron-Cohen, S., Auyeung, B., Norgaard-Pedersen, B., Hougaard, D. M., Abdallah, M. W., Melgaard, L., Lombardo, M. V. (2015). Elevated fetal steroidogenic activity in autism. Mol Psychiatry, 20(3), 369-376. doi:10.1038/mp.2014.48
5. Baron-Cohen, S., Knickmeyer, R. C., & Belmonte, M. K. (2005). Sex differences in the brain: implications for explaining autism. Science, 310(5749), 819-823.
6. Bergman, Å., Heindel, J. J., Jobling, S., Kidd, K., Zoeller, T. R., & Organization, W. H. (2013). State of the science of endocrine disrupting chemicals 2012: summary for decision-makers.
7. Braun, J. M., Muckle, G., Arbuckle, T., Bouchard, M. F., Fraser, W. D., Ouellet, E., Lanphear, B. P. (2017). Associations of Prenatal Urinary Bisphenol A Concentrations with Child Behaviors and Cognitive Abilities. Environ Health Perspect, 125(6), 067008. doi:10.1289/EHP984
8. Cheslack-Postava, K., Rantakokko, P. V., Hinkka-Yli-Salomaki, S., Surcel, H. M., McKeague, I. W., Kiviranta, H. A., Brown, A. S. (2013). Maternal serum persistent organic pollutants in the Finnish Prenatal Study of Autism: A pilot study. Neurotoxicol Teratol, 38, 1-5. doi:10.1016/j.ntt.2013.04.001

9. Chevrier, J., Gunier, R. B., Bradman, A., Holland, N. T., Calafat, A. M., Eskenazi, B., & Harley, K. G. (2013). Maternal urinary bisphenol a during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study. Environ Health Perspect, 121(1), 138-144. doi:10.1289/ehp.1205092
10. Christensen, D. L., Bilder, D. A., Zahorodny, W., Pettygrove, S., Durkin, M. S., Fitzgerald, R. T., Yeargin-Allsopp, M. (2016). Prevalence and characteristics of autism spectrum disorder among 4-year-old children in the autism and developmental disabilities monitoring network. Journal of Developmental & Behavioral Pediatrics, 37(1), 1-8.
11. Çetinkaya, S. (2009). Endokrin çevre bozucular ve ergenlik üzerine etkileri. Dicle Tıp Dergisi, 36(1).
12. Damstra, T., Barlow, S., Bergman, A., Kavlock, R., & Van Der Kraak, G. (2002). Global assessment of the state-of-the-science of endocrine disruptors. Geneva: World Health Organization.
13. de Cock, M., Maas, Y. G., & van de Bor, M. (2012). Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders? Review. Acta Paediatr, 101(8), 811-818. doi:10.1111/j.1651-2227.2012.02693.x
14. De Luca, F. (2016). Endocrinological Abnormalities in Autism. Seminars in Pediatric Neurology. doi:10.1016/j.spen.2016.04.001
15. Domingues, V., Nasuti, C., Piangerelli, M., Correia-Sá, L., Ghezzo, A., Marini, M., Gabbianelli, R. (2016). Pyrethroid Pesticide Metabolite in Urine and Microelements in Hair of Children Affected by Autism Spectrum Disorders: A Preliminary Investigation. International Journal of Environmental Research and Public Health, 13(12), 388. doi:10.3390/ijerph13040388
16. Eskenazi, B., Rauch, S. A., Tenerelli, R., Huen, K., Holland, N. T., Lustig, R. H., Harley, K. G. (2017). In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: The CHAMACOS study. Int J Hyg Environ Health, 220(2 Pt B), 364-372. doi:10.1016/j.ijheh.2016.11.001
17. Grandjean, P., & Jensen, A. A. (2004). Breastfeeding and the weanling’s dilemma. American journal of public health, 94(7), 1075-1075.
18. Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., Risch, N. (2011). Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry, 68(11), 1095-1102. doi:10.1001/archgenpsychiatry.2011.76
19. Hertz-Picciotto, I., & Delwiche, L. (2009). The rise in autism and the role of age at diagnosis. Epidemiology, 20(1), 84-90. doi:10.1097/EDE.0b013e3181902d15
20. Hu, V. W. (2012). Is retinoic acid-related orphan receptor-alpha (RORA) a target for gene-environment interactions contributing to autism? Neurotoxicology, 33(6), 1434-1435. doi:10.1016/j.neuro.2012.07.009
21. Johns, L. E., Ferguson, K. K., Soldin, O. P., Cantonwine, D. E., Rivera-González, L. O., Del Toro, L. V. A., Cordero, J. F. (2015). Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis. Reproductive Biology and Endocrinology, 13(1), 4.
22. Kardas, F., Bayram, A. K., Demirci, E., Akin, L., Ozmen, S., Kendirci, M., Per, H. (2016). Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder: The Role of Endocrine Disruptors in Autism Etiopathogenesis. J Child Neurol, 31(5), 629-635. doi:10.1177/0883073815609150
23. Kinch, C. D., Ibhazehiebo, K., Jeong, J. H., Habibi, H. R., & Kurrasch, D. M. (2015). Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish. Proc Natl Acad Sci U S A, 112(5), 1475-1480. doi:10.1073/pnas.1417731112
24. Knickmeyer, R., Baron-Cohen, S., Raggatt, P., & Taylor, K. (2005). Foetal testosterone, social relationships, and restricted interests in children. J Child Psychol Psychiatry, 46(2), 198-210. doi:10.1111/j.1469-7610.2004.00349.x
25. Kondolot, M., Ozmert, E. N., Asci, A., Erkekoglu, P., Oztop, D. B., Gumus, H., Yurdakok, K. (2016). Plasma phthalate and bisphenol a levels and oxidant-antioxidant status in autistic children. Environ Toxicol Pharmacol, 43, 149-158. doi:10.1016/j.etap.2016.03.006
26. Kortenkamp, A., Martin, O., Faust, M., Evans, R., McKinlay, R., Orton, F., & Rosivatz, E. (2011). State of the art assessment of endocrine disrupters. Final report, 23.
27. Kumamoto, T., & Oshio, S. (2013). Effect of fetal exposure to bisphenol A on brain mediated by X-chromosome inactivation. The Journal of toxicological sciences, 38(3), 485-494.
28. Larsson, M., Weiss, B., Janson, S., Sundell, J., & Bornehag, C. G. (2009). Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age. Neurotoxicology, 30(5), 822-831. doi:10.1016/j.neuro.2009.01.011
29. Liew, Z., Ritz, B., von Ehrenstein, O. S., Bech, B. H., Nohr, E. A., Fei, C., Olsen, J. (2015). Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case-control study in the Danish National Birth Cohort. Environ Health Perspect, 123(4), 367-373. doi:10.1289/ehp.1408412
30. Lyall, K., Croen, L. A., Sjodin, A., Yoshida, C. K., Zerbo, O., Kharrazi, M., & Windham, G. C. (2017). Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability. Environ Health Perspect, 125(3), 474-480. doi:10.1289/EHP277
31. Mohamed Fel, B., Zaky, E. A., El-Sayed, A. B., Elhossieny, R. M., Zahra, S. S., Salah Eldin, W., Youssef, A. M. (2015). Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism. Behav Neurol, 2015, 545674. doi:10.1155/2015/545674
32. Moosa, A., Shu, H., Sarachana, T., & Hu, V. W. (2017). Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder? Horm Behav. doi:10.1016/j.yhbeh.2017.10.003
33. Nguyen, A., Rauch, T. A., Pfeifer, G. P., & Hu, V. W. (2010). Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J, 24(8), 3036-3051. doi:10.1096/fj.10-154484
34. Park, B. Y., Lee, B. K., Burstyn, I., Tabb, L. P., Keelan, J. A., Whitehouse, A. J. O., Newschaffer, C. J. (2017). Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study. Mol Autism, 8, 3. doi:10.1186/s13229-017-0118-z
35. Rebuli, M. E., & Patisaul, H. B. (2016). Assessment of sex specific endocrine disrupting effects in the prenatal and pre-pubertal rodent brain. J Steroid Biochem Mol Biol, 160, 148-159. doi:10.1016/j.jsbmb.2015.08.021
36. Sarachana, T., & Hu, V. W. (2013). Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder. Molecular autism, 4(1), 14.
37. Sarachana, T., Xu, M., Wu, R. C., & Hu, V. W. (2011). Sex hormones in autism: androgens and estrogens differentially and reciprocally regulate RORA, a novel candidate gene for autism. PLoS One, 6(2), e17116. doi:10.1371/journal.pone.0017116
38. Shelton, J. F., Geraghty, E. M., Tancredi, D. J., Delwiche, L. D., Schmidt, R. J., Ritz, B., Hertz-Picciotto, I. (2014). Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect, 122(10), 1103-1109. doi:10.1289/ehp.1307044
39. Stein, T. P., Schluter, M. D., Steer, R. A., Guo, L., & Ming, X. (2015). Bisphenol A Exposure in Children With Autism Spectrum Disorders. Autism Res, 8(3), 272-283. doi:10.1002/aur.1444
40. Tordjman, S., Somogyi, E., Coulon, N., Kermarrec, S., Cohen, D., Bronsard, G., Xavier, J. (2014). Gene x Environment interactions in autism spectrum disorders: role of epigenetic mechanisms. Front Psychiatry, 5, 53. doi:10.3389/fpsyt.2014.00053
41. Wolstenholme, J. T., Edwards, M., Shetty, S. R., Gatewood, J. D., Taylor, J. A., Rissman, E. F., & Connelly, J. J. (2012). Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression. Endocrinology, 153(8), 3828-3838.
42. Vrijheid, M., Casas, M., Gascon, M., Valvi, D., & Nieuwenhuijsen, M. (2016). Environmental pollutants and child health—a review of recent concerns. International journal of hygiene and environmental health, 219(4-5), 331-342.