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Cited by 73Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersEstrogen and related hormone effects

Endocrine disruptors as a threat to neurological function

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Weiss, Bernard·2011·Journal of the Neurological Sciences
DOI 10.1016/j.jns.2011.03.014PMC PMC3090512
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Abstract

Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer.

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  • Products such as baby bottles, inner coatings of food cans, microwave dishes, and dental sealants are important sources of human exposure to BPA.

    “Products such as baby bottles, the inner coatings of food cans, microwave dishes and even dental sealants are important sources of human exposure (Weiss, 2011, 2007).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Weiss, 2011

    In “Neurodevelopmental Implications > Animal studies” (page unavailable), Weiss says BPA occurs in many products and is released into the environment, including food products, making human exposure widespread. The available text does not identify baby bottles, can linings, microwave dishes, or dental sealants as exposure sources. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • EDCs are widespread in the environment, may accumulate in organisms, and often exert biological effects even at low, environmentally relevant doses.

    “EDCs are widespread in the environment, may accumulate in organisms, and often exert biological effects even at low, environmentally relevant doses (Weiss, 2011).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Weiss, 2011

    In Neurodevelopmental Implications (Animal studies), Weiss describes widespread BPA exposure and reports biological effects at low doses, including effects discussed at environmental exposure levels. The Human studies section says phthalates are ubiquitous in human tissue. Neither section establishes that EDCs accumulate in organisms; detection in tissue is not evidence of accumulation over time. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Sex-dependent effects in motor development have been reported, differing according to the specific phthalate involved.

    “Sex-dependent effects have also been reported, particularly in motor development, which differed according to the specific phthalate involved (Schug et al., 2015; Weiss, 2011).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Weiss, 2011

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Research works printed but not linked: 75

  1. [3]Hunt GL Jr Hunt MW Female-Female Pairing in Western Gulls (Larus occidentalis) in Southern California Science 1977 196 1466 1467 17776927
  2. [4]Fry DM Reproductive effects in birds exposed to pesticides and industrial chemicals Environ. Health Perspect 1995 103 Suppl 7 165 171 8593865 PMC1518881
  3. [5]Carlsen E Giwercman A Keiding N Skakkebaek NE Evidence for decreasing quality of semen during past 50 years BMJ 1992 305 609 613 1393072 PMC1883354
  4. [6]Sharpe RM Skakkebaek NE Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 1993 341 1392 1395 8098802
  5. [8]Moller H Trends in sex-ratio, testicular cancer and male reproductive hazards: are they connected? APMIS 1998 106 232 238 9524584
  6. [9]Andersson AM Jorgensen N Main KM Toppari J Rajpert-De Meyts E Leffers H Adverse trends in male reproductive health: we may have reached a crucial 'tipping point' Int. J. Androl 2008 31 74 80 18194282 PMC2440492
  7. [10]Skakkebaek NE Testicular dysgenesis syndrome Horm. Res 2003 60 Suppl 3 49 14671395
  8. [11]Guillette LJ Jr Gross TS Masson GR Matter JM Percival HF Woodward AR Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida Environ. Health Perspect 1994 102 680 688 7895709 PMC1567320
  9. [12]Colborn T vom Saal FS Soto AM Developmental effects of endocrine-disrupting chemicals in wildlife and humans Environ. Health Perspect 1993 101 378 384 8080506 PMC1519860
  10. [14]Sharpe RM "Additional" effects of phthalate mixtures on fetal testosterone production Toxicol.Sci 2008 105 1 4 18579535
  11. [15]Zoeller RT Environmental chemicals impacting the thyroid: targets and consequences Thyroid 2007 17 811 817 17956155
  12. [16]Arnold AP Sex chromosomes and brain gender Nat Rev Neurosci 2004 5 701 728 15322528
  13. [17]Swaab DF Sexual differentiation of the brain and behavior Best Pract. Res. Clin. Endocrinol. Metab 2007 21 431 444 17875490
  14. [18]Goldstein JM Seidman LJ Horton NJ Makris N Kennedy DN Caviness VS Jr Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging Cereb. Cortex 2001 11 490 497 11375910
  15. [19]Kimura D Sex, sexual orientation and sex hormones influence human cognitive function Curr. Opin. Neurobiol 1996 6 259 263 8725969
  16. [21]Hany J Lilienthal H Sarasin A Roth-Harer A Fastabend A Dunemann L Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on organ weights, aromatase activity, sex hormone levels, and sweet preference behavior Toxicol. Appl. Pharmacol 1999 158 231 243 10438656
  17. [22]Amin S Moore RW Peterson RE Schantz SL Gestational and lactational exposure to TCDD or coplanar PCBs alters adult expression of saccharin preference behavior in female rats Neurotoxicol. Teratol 2000t 22 675 682 11106860
  18. [23]Hojo R Stern S Zareba G Markowski VP Cox C Kost JT Weiss B Sexually dimorphic behavioral responses to prenatal dioxin exposure Environ. Health Perspect 2002 110 247 254 11882475 PMC1240764
  19. [24]Hotchkiss AK Ostby JS Vandenbergh JG Gray LE Jr An environmental antiandrogen, vinclozolin, alters the organization of play behavior Physiol. Behav 2003 79 151 156 12834785
  20. [26]Andre SM Markowski VP Learning deficits expressed as delayed extinction of a conditioned running response following perinatal exposure to vinclozolin Neurotoxicol. Teratol 2006 28 482 488 16765025
  21. [27]Gray LE Jr Ostby J Cooper RL Kelce WR The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats Toxicol. Ind. Health 1999 15 37 47 10188190
  22. [28]Murono EP Derk RC The reported active metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits testosterone formation by cultured Leydig cells from neonatal rats Reprod. Toxicol 2005 20 503 513 16199348
  23. [29]Gioiosa L Fissore E Ghirardelli G Parmigiani S Palanza P Developmental exposure to low-dose estrogenic endocrine disruptors alters sex differences in exploration and emotional responses in mice Horm. Behav 2007 52 307 316 17568585
  24. [30]Richter CA Birnbaum LS Farabollini F Newbold RR Rubin BS Talsness CE In vivo effects of bisphenol A in laboratory rodent studies Reprod. Toxicol 2007 24 199 224 17683900 PMC2151845
  25. [31]Chapin RE Adams J Boekelheide K Gray LE Jr Hayward SW Lees PS NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A Birth Defects Res. B. Dev. Reprod. Toxicol 2008 83 157 395 18613034
  26. [32]vom Saal FS Akingbemi BT Belcher SM Birnbaum LS Crain DA Eriksen M Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure Reprod. Toxicol 2007 24 131 138 17768031 PMC2967230
  27. [33]Welshons WV Nagel SC vom Saal FS Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure Endocrinology 2006 147 6 Suppl S56 S69 16690810
  28. [34]Andrade AJ Grande SW Talsness CE Grote K Chahoud I A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on rat brain aromatase activity Toxicology 2006 227 185 192 16949715
  29. [35]Rubin BS Lenkowski JR Schaeberle CM Vandenberg LN Ronsheim PM Soto AM Evidence of altered brain sexual differentiation in mice exposed perinatally to low, environmentally relevant levels of bisphenol A Endocrinology 2006 147 3681 3691 16675520
  30. [36]Farabollini F Porrini S Della Seta D Bianchi F Dessi-Fulgheri F Effects of perinatal exposure to bisphenol A on sociosexual behavior of female and male rats Environ. Health Perspect 2002 110 Suppl 3 409 414 12060837 PMC1241191
  31. [37]Della Seta D Minder I Dessi-Fulgheri F Farabollini F Bisphenol-A exposure during pregnancy and lactation affects maternal behavior in rats Brain Res. Bull 2005 65 255 260 15811589
  32. [38]Anway MD Cupp AS Uzumcu M Skinner MK Epigenetic transgenerational actions of endocrine disruptors and male fertility Science 2005 308 1466 1469 15933200 PMC11423801
  33. [39]Anway MD Skinner MK Epigenetic programming of the germ line: effects of endocrine disruptors on the development of transgenerational disease Reprod. Biomed. Online 2008 16 23 25 18252044 PMC5940337
  34. [40]Crews D Gore AC Hsu TS Dangleben NL Spinetta M Schallert T Transgenerational epigenetic imprints on mate preference Proc. Natl. Acad. Sci.U.S.A 2007 104 5942 5946 17389367 PMC1851596
  35. [41]Skinner MK Anway MD Savenkova MI Gore AC Crews D Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior PLoS One 2008 3 e3745 19015723 PMC2581440
  36. [42]Swan SH Main KM Liu F Stewart SL Kruse RL Calafat AM Decrease in anogenital distance among male infants with prenatal phthalate exposure Environ Health Perspect 2005 113 1056 1061 16079079 PMC1280349
  37. [43]Sharpe RM Phthalate exposure during pregnancy and lower anogenital index in boys: wider implications for the general population? Environ. Health Perspect 2005 113 A504 A505 16079047 PMC1280357
  38. [44]Swan SH Liu F Hines M Kruse RL Wang C Redmon JB Sparks A Weiss B Prenatal phthalate exposure and reduced masculine play in boys Int. J. Androl 2010 33 259 269 19919614 PMC2874619
  39. [45]Golombok S Rust J The measurement of gender role behaviour in pre-school children: a research note J. Child Psychol. Psychiatry 1993 34 805 811 8340446
  40. [46]Golombok S Rust J Zervoulis K Croudace T Golding J Hines M Developmental trajectories of sex-typed behavior in boys and girls: a longitudinal general population study of children aged 2.5–8 years Child Dev 2008 79 1583 1593 18826544
  41. [47]Kim BN Cho SC Kim Y Shin MS Yoo HJ Kim JW Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children Biol. Psychiatry 2009 66 958 963 19748073
  42. [48]Engel SM Zhu C Berkowitz GS Calafat AM Silva MJ Miodovnik A Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort Neurotoxicology 2009 30 522 528 19375452 PMC4026936
  43. [49]Bornehag CG Sundell J Weschler CJ Sigsgaard T Lundgren B Hasselgren M The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case-control study Environ. Health Perspect 2004 112 1393 1397 15471731 PMC1247566
  44. [51]Braun JM Yolton K Dietrich KM Hornung R Ye X Calafat AM Prenatal Bisphenol A Exposure and Early Childhood Behavior Environ. Health Perspect 2009 117 1945 1952 20049216 PMC2799471
  45. [52]Weiss B Clarkson TW Simon W Silent latency periods in methylmercury poisoning and in neurodegenerative disease Environ. Health Perspect 2002 110 Suppl 5 851 854 12426145 PMC1241259
  46. [53]Hof PR Morrison JH The aging brain: morphomolecular senescence of cortical circuits Trends Neurosci 2004 27 607 613 15374672
  47. [54]Rapp PR Morrison JH Roberts JA Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys J.Neurosci 2003 23 5708 5714 12843274 PMC6741262
  48. [55]Hao J Rapp PR Leffler AE Leffler SR Janssen WG Lou W Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys J. Neurosci 2006 26 2571 2578 16510735 PMC6793646
  49. [56]Kempermann G Gage FH Closer to neurogenesis in adult humans Nat. Med 1998 4 555 557 9585224
  50. [57]Eriksson PS Perfilieva E Bjork-Eriksson T Alborn AM Nordborg C Peterson DA Neurogenesis in the adult human hippocampus Nat. Med 1998 4 1313 1317 9809557
  51. [58]Gross CG Neurogenesis in the adult brain: death of a dogma Nat. Rev. Neurosci 2000 1 67 73 11252770
  52. [59]Alvarez-Buylla A Lim DA For the long run: maintaining germinal niches in the adult brain Neuron 2004 41 683 686 15003168
  53. [60]Kempermann G Wiskott L Gage FH Functional significance of adult neurogenesis Curr. Opin. Neurobiol 2004 14 186 191 15082323
  54. [61]Weiss B Can endocrine disruptors influence neuroplasticity in the aging brain? Neurotoxicology 2007 28 938 950 17350099 PMC2072817
  55. [62]Woolley CS Gould E Frankfurt M McEwen BS Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons J. Neurosci 1990 10 4035 4039 2269895 PMC6570039
  56. [63]Woolley CS McEwen BS Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat J. Neurosci 1992 12 2549 2554 1613547 PMC6575846
  57. [64]Cooke BM Woolley CS Gonadal hormone modulation of dendrites in the mammalian CNS J. Neurobiol 2005 64 34 46 15884004
  58. [65]Tanapat P Hastings NB Gould E Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose- and time-dependent manner J. Comp. Neurol 2005 481 252 265 15593136
  59. [66]Leranth C Petnehazy O MacLusky NJ Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats J. Neurosci 2003 23 1588 1592 12629162 PMC6741990
  60. [68]Yaffe K Lui LY Zmuda J Cauley J Sex hormones and cognitive function in older men J. Am. Geriatr. Soc 2002 50 707 712 11982672
  61. [69]Yaffe K Testosterone and the brain: uncharted territory Lancet Neurol 2004 3 270 15099540
  62. [71]Janowsky JS Thinking with your gonads: testosterone and cognition Trends Cogn. Sci 10 77 82 16386941
  63. [72]Hogervorst E Bandelow S Combrinck M Smith AD Low free testosterone is an independent risk factor for Alzheimer's disease Exp. Gerontol 2004 39 1633 1639 15582279
  64. [73]MacLusky NJ Hajszan T Prange-Kiel J Leranth C Androgen modulation of hippocampal synaptic plasticity Neuroscience 2006 138 957 965 16488544
  65. [74]Zandi PP Carlson MC Plassman BL Welsh-Bohmer KA Mayer LS Steffens DC Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study JAMA 2002 288 2123 2129 12413371
  66. [75]Sherwin BB Estrogen and cognitive aging in women Neuroscience 2006 138 1021 1026 16310965
  67. [76]Espeland MA Rapp SR Shumaker SA Brunner R Manson JE Sherwin BB Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study JAMA 2004 291 2959 2968 15213207
  68. [77]Shumaker SA Legault C Kuller L Rapp SR Thal L Lane DS Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study JAMA 2004 291 2947 2958 15213206
  69. [78]MacLennan AH Henderson VW Paine BJ Mathias J Ramsay EN Ryan P Hormone therapy, timing of initiation, and cognition in women aged older than 60 years: the REMEMBER pilot study Menopause 2006 13 28 36 16607096
  70. [79]MacLusky NJ Hajszan T Leranth C The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis Environ. Health Perspect 2005 113 675 679 15929888 PMC1257590
  71. [80]Leranth C Hajszan T Szigeti-Buck K Bober J MacLusky NJ Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates Proc. Natl. Acad. Sci.U.S.A 2008 105 14187 14191 18768812 PMC2544599
  72. [81]Meeker JD Calafat AM Hauser R Urinary Metabolites of di(2-ethylhexyl) phthalate Are associated with decreased steroid hormone levels in adult men J Androl 2009 30 287 297 19059903 PMC2772199
  73. [82]Stahlhut RW van Wijngaarden E Dye TD Cook S Swan SH Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males Environ. Health Perspect 2007 115 876 882 17589594 PMC1892109
  74. [83]Lang IA Galloway TS Scarlett A Henley WE Depledge M Wallace RB Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults JAMA 2008 300 1303 1310 18799442
  75. [85]Cahill L Why sex matters for neuroscience Nat. Rev. Neurosci 2006 7 477 484 16688123

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Authors
Weiss, B.
Affiliations
University of Rochester Medicine (US)
Corresponding author
Weiss, Bernard
ORCID
Weiss, Bernard
Venue
Journal of the Neurological Sciences
Publisher
Elsevier BV
Published
2011-06
Volume
305
Issue
1-2
Pages
11-21
ISSN
0022-510X (ISSN-L)
DOI
10.1016/j.jns.2011.03.014
PMC
PMC3090512
OpenAlex
W2000474839
Cited by
73
References
6
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 4
FWCI
0.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the Neurological Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Environmental Health Sciences
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
endocrine disruptors, neurological function, gonadal hormones, sexual differentiation of the brain, neurogenesis, brain aging, neurodegeneration, dementia, cognitive function, male reproductive disorders, DDT, organochlorine pesticides, fertility decline
MeSH terms
Animals, Humans, Nervous System Malformations, Disorders of Sex Development, Gonadal Steroid Hormones, Hazardous Substances, Endocrine Disruptors

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