Endocrine disruptors as a threat to neurological function

  • Bernard Weiss
    Correspondence
    University of Rochester Medical Center, 610 Elmwood Avenue, Rochester, NY 14642, USA. Tel.: +1 585 275 1736; fax: +1 585 256 2591.
    Affiliations
    Department of Environmental Medicine, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA
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Published:April 08, 2011DOI:https://doi.org/10.1016/j.jns.2011.03.014

      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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      References

        • Carson R.
        Silent spring. Houghton Mifflin, New York1962
      1. Berg G.C. Miller M.W. Chemical fallout. Charles C. Thomas, Springfield, IL1969
        • Hunt Jr., G.L.
        • Hunt M.W.
        Female–female pairing in Western gulls (Larus occidentalis) in Southern California.
        Science. 1977; 196: 1466-1467
        • Fry D.M.
        Reproductive effects in birds exposed to pesticides and industrial chemicals.
        Environ Health Perspect. 1995; 103: 165-171
        • Carlsen E.
        • Giwercman A.
        • Keiding N.
        • Skakkebaek N.E.
        Evidence for decreasing quality of semen during past 50 years.
        BMJ. 1992; 305: 609-613
        • Sharpe R.M.
        • Skakkebaek N.E.
        Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract?.
        Lancet. 1993; 341: 1392-1395
        • James P.D.
        The children of men. Knopf, New York1993
        • Moller H.
        Trends in sex-ratio, testicular cancer and male reproductive hazards: are they connected?.
        APMIS. 1998; 106: 232-238
        • Andersson A.M.
        • Jorgensen N.
        • Main K.M.
        • Toppari J.
        • Rajpert-De Meyts E.
        • Leffers H.
        • et al.
        Adverse trends in male reproductive health: we may have reached a crucial ‘tipping point’.
        Int J Androl. 2008; 31: 74-80
        • Skakkebaek N.E.
        Testicular dysgenesis syndrome.
        Horm Res. 2003; 60: 49
        • Guillette Jr., L.J.
        • Gross T.S.
        • Masson G.R.
        • Matter J.M.
        • Percival H.F.
        • Woodward A.R.
        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
        • Colborn T.
        • vom Saal F.S.
        • Soto A.M.
        Developmental effects of endocrine-disrupting chemicals in wildlife and humans.
        Environ Health Perspect. 1993; 101: 378-384
        • Colborn T.
        • Dumanoski D.
        • Myers J.M.
        Our stolen future. Dutton, New York1996
        • Sharpe R.M.
        “Additional” effects of phthalate mixtures on fetal testosterone production.
        Toxicol Sci. 2008; 105: 1-4
        • Zoeller R.T.
        Environmental chemicals impacting the thyroid: targets and consequences.
        Thyroid. 2007; 17: 811-817
        • Arnold A.P.
        Sex chromosomes and brain gender.
        Nat Rev Neurosci. 2004; 5: 701-728
        • Swaab D.F.
        Sexual differentiation of the brain and behavior.
        Best Pract Res Clin Endocrinol Metab. 2007; 21: 431-444
        • Goldstein J.M.
        • Seidman L.J.
        • Horton N.J.
        • Makris N.
        • Kennedy D.N.
        • Caviness Jr., V.S.
        • et al.
        Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging.
        Cereb Cortex. 2001; 11: 490-497
        • Kimura D.
        Sex, sexual orientation and sex hormones influence human cognitive function.
        Curr Opin Neurobiol. 1996; 6: 259-263
        • Hines M.
        Prenatal testosterone and gender-related behaviour.
        Eur J Endocrinol. 2006; 155: S115-S121
        • Hany J.
        • Lilienthal H.
        • Sarasin A.
        • Roth-Harer A.
        • Fastabend A.
        • Dunemann L.
        • et al.
        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
        • Amin S.
        • Moore R.W.
        • Peterson R.E.
        • Schantz S.L.
        Gestational and lactational exposure to TCDD or coplanar PCBs alters adult expression of saccharin preference behavior in female rats.
        Neurotoxicol Teratol. 2000; 22: 675-682
        • Hojo R.
        • Stern S.
        • Zareba G.
        • Markowski V.P.
        • Cox C.
        • Kost J.T.
        • et al.
        Sexually dimorphic behavioral responses to prenatal dioxin exposure.
        Environ Health Perspect. 2002; 110: 247-254
        • Hotchkiss A.K.
        • Ostby J.S.
        • Vandenbergh J.G.
        • Gray Jr., L.E.
        An environmental antiandrogen, vinclozolin, alters the organization of play behavior.
        Physiol Behav. 2003; 79: 151-156
        • Colbert N.K.
        • Pelletier N.C.
        • Cote J.M.
        • Concannon J.B.
        • Jurdak N.A.
        • Minott S.B.
        • et al.
        Perinatal exposure to low levels of the environmental antiandrogen vinclozolin alters sex-differentiated social play and sexual behaviors in the rat.
        Environ Health Perspect. 2005; 113: 700-707
        • Andre S.M.
        • Markowski V.P.
        Learning deficits expressed as delayed extinction of a conditioned running response following perinatal exposure to vinclozolin.
        Neurotoxicol Teratol. 2006; 28: 482-488
        • Gray Jr., L.E.
        • Ostby J.
        • Cooper R.L.
        • Kelce W.R.
        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
        • Murono E.P.
        • Derk R.C.
        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
        • 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
        • Richter C.A.
        • Birnbaum L.S.
        • Farabollini F.
        • Newbold R.R.
        • Rubin B.S.
        • Talsness C.E.
        • et al.
        In vivo effects of bisphenol A in laboratory rodent studies.
        Reprod Toxicol. 2007; 24: 199-224
        • Chapin R.E.
        • Adams J.
        • Boekelheide K.
        • Gray Jr., L.E.
        • Hayward S.W.
        • Lees P.S.
        • et al.
        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
        • vom Saal F.S.
        • Akingbemi B.T.
        • Belcher S.M.
        • Birnbaum L.S.
        • Crain D.A.
        • Eriksen M.
        • et al.
        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
        • Welshons W.V.
        • Nagel S.C.
        • vom Saal F.S.
        Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure.
        Endocrinology. 2006; 147: S56-S69
        • Andrade A.J.
        • Grande S.W.
        • Talsness C.E.
        • 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
        • Rubin B.S.
        • Lenkowski J.R.
        • Schaeberle C.M.
        • Vandenberg L.N.
        • Ronsheim P.M.
        • Soto A.M.
        Evidence of altered brain sexual differentiation in mice exposed perinatally to low, environmentally relevant levels of bisphenol A.
        Endocrinology. 2006; 147: 3681-3691
        • 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: 409-414
        • 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
        • Anway M.D.
        • Cupp A.S.
        • Uzumcu M.
        • Skinner M.K.
        Epigenetic transgenerational actions of endocrine disruptors and male fertility.
        Science. 2005; 308: 1466-1469
        • Anway M.D.
        • Skinner M.K.
        Epigenetic programming of the germ line: effects of endocrine disruptors on the development of transgenerational disease.
        Reprod Biomed Online. 2008; 16: 23-25
        • Crews D.
        • Gore A.C.
        • Hsu T.S.
        • Dangleben N.L.
        • Spinetta M.
        • Schallert T.
        • et al.
        Transgenerational epigenetic imprints on mate preference.
        Proc Natl Acad Sci U S A. 2007; 104: 5942-5946
        • Skinner M.K.
        • Anway M.D.
        • Savenkova M.I.
        • Gore A.C.
        • Crews D.
        Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.
        PLoS ONE. 2008; 3: e3745
        • Swan S.H.
        • Main K.M.
        • Liu F.
        • Stewart S.L.
        • Kruse R.L.
        • Calafat A.M.
        • et al.
        Decrease in anogenital distance among male infants with prenatal phthalate exposure.
        Environ Health Perspect. 2005; 113: 1056-1061
        • Sharpe R.M.
        Phthalate exposure during pregnancy and lower anogenital index in boys: wider implications for the general population?.
        Environ Health Perspect. 2005; 113: A504-A505
        • Swan S.H.
        • Liu F.
        • Hines M.
        • Kruse R.L.
        • Wang C.
        • Redmon J.B.
        • et al.
        Prenatal phthalate exposure and reduced masculine play in boys.
        Int J Androl. 2010; 33: 259-269
        • 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
        • 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
        • Kim B.N.
        • Cho S.C.
        • Kim Y.
        • Shin M.S.
        • Yoo H.J.
        • Kim J.W.
        • et al.
        Phthalates exposure and attention-deficit/hyperactivity disorder in school-age children.
        Biol Psychiatry. 2009; 66: 958-963
        • Engel S.M.
        • Zhu C.
        • Berkowitz G.S.
        • Calafat A.M.
        • Silva M.J.
        • Miodovnik A.
        • et al.
        Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort.
        Neurotoxicology. 2009; 30: 522-528
        • Bornehag C.G.
        • Sundell J.
        • Weschler C.J.
        • Sigsgaard T.
        • Lundgren B.
        • Hasselgren M.
        • et al.
        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
        • Larsson M.
        • Weiss B.
        • Janson S.
        • Sundell J.
        • Bornehag C.G.
        Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6–8 years of age.
        Neurotoxicology. 2009; 30: 822-831
        • Braun J.M.
        • Yolton K.
        • Dietrich K.M.
        • Hornung R.
        • Ye X.
        • Calafat A.M.
        • et al.
        Prenatal bisphenol A exposure and early childhood behavior.
        Environ Health Perspect. 2009; 117: 1945-1952
        • Weiss B.
        • Clarkson T.W.
        • Simon W.
        Silent latency periods in methylmercury poisoning and in neurodegenerative disease.
        Environ Health Perspect. 2002; 110: 851-854
        • Hof P.R.
        • Morrison J.H.
        The aging brain: morphomolecular senescence of cortical circuits.
        Trends Neurosci. 2004; 27: 607-613
        • Rapp P.R.
        • Morrison J.H.
        • Roberts J.A.
        Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys.
        J Neurosci. 2003; 23: 5708-5714
        • Hao J.
        • Rapp P.R.
        • Leffler A.E.
        • Leffler S.R.
        • Janssen W.G.
        • Lou W.
        • et al.
        Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys.
        J Neurosci. 2006; 26: 2571-2578
        • Kempermann G.
        • Gage F.H.
        Closer to neurogenesis in adult humans.
        Nat Med. 1998; 4: 555-557
        • Eriksson P.S.
        • Perfilieva E.
        • Bjork-Eriksson T.
        • Alborn A.M.
        • Nordborg C.
        • Peterson D.A.
        • et al.
        Neurogenesis in the adult human hippocampus.
        Nat Med. 1998; 4: 1313-1317
        • Gross C.G.
        Neurogenesis in the adult brain: death of a dogma.
        Nat Rev Neurosci. 2000; 1: 67-73
        • Alvarez-Buylla A.
        • Lim D.A.
        For the long run: maintaining germinal niches in the adult brain.
        Neuron. 2004; 41: 683-686
        • Kempermann G.
        • Wiskott L.
        • Gage F.H.
        Functional significance of adult neurogenesis.
        Curr Opin Neurobiol. 2004; 14: 186-191
        • Weiss B.
        Can endocrine disruptors influence neuroplasticity in the aging brain?.
        Neurotoxicology. 2007; 28: 938-950
        • Woolley C.S.
        • Gould E.
        • Frankfurt M.
        • McEwen B.S.
        Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons.
        J Neurosci. 1990; 10: 4035-4039
        • Woolley C.S.
        • McEwen B.S.
        Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat.
        J Neurosci. 1992; 12: 2549-2554
        • Cooke B.M.
        • Woolley C.S.
        Gonadal hormone modulation of dendrites in the mammalian CNS.
        J Neurobiol. 2005; 64: 34-46
        • Tanapat P.
        • Hastings N.B.
        • 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
        • Leranth C.
        • Petnehazy O.
        • MacLusky N.J.
        Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats.
        J Neurosci. 2003; 23: 1588-1592
        • Hijazi R.A.
        • Cunningham G.R.
        Andropause: is androgen replacement therapy indicated for the aging male?.
        Annu Rev Med. 2005; 56: 117-137
        • Yaffe K.
        • Lui L.Y.
        • Zmuda J.
        • Cauley J.
        Sex hormones and cognitive function in older men.
        J Am Geriatr Soc. 2002; 50: 707-712
        • Yaffe K.
        Testosterone and the brain: uncharted territory.
        Lancet Neurol. 2004; 3: 270
        • Moffat S.D.
        Effects of testosterone on cognitive and brain aging in elderly men.
        Ann N Y Acad Sci. 2005; 1055: 80-92
        • Janowsky J.S.
        Thinking with your gonads: testosterone and cognition.
        Trends Cogn Sci. 2006; 10: 77-82
        • Hogervorst E.
        • Bandelow S.
        • Combrinck M.
        • Smith A.D.
        Low free testosterone is an independent risk factor for Alzheimer's disease.
        Exp Gerontol. 2004; 39: 1633-1639
        • MacLusky N.J.
        • Hajszan T.
        • Prange-Kiel J.
        • Leranth C.
        Androgen modulation of hippocampal synaptic plasticity.
        Neuroscience. 2006; 138: 957-965
        • Zandi P.P.
        • Carlson M.C.
        • Plassman B.L.
        • Welsh-Bohmer K.A.
        • Mayer L.S.
        • Steffens D.C.
        • et al.
        Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study.
        JAMA. 2002; 288: 2123-2129
        • Sherwin B.B.
        Estrogen and cognitive aging in women.
        Neuroscience. 2006; 138: 1021-1026
        • Espeland M.A.
        • Rapp S.R.
        • Shumaker S.A.
        • Brunner R.
        • Manson J.E.
        • Sherwin B.B.
        • et al.
        Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.
        JAMA. 2004; 291: 2959-2968
        • Shumaker S.A.
        • Legault C.
        • Kuller L.
        • Rapp S.R.
        • Thal L.
        • Lane D.S.
        • et al.
        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
        • MacLennan A.H.
        • Henderson V.W.
        • Paine B.J.
        • Mathias J.
        • Ramsay E.N.
        • Ryan P.
        • et al.
        Hormone therapy, timing of initiation, and cognition in women aged older than 60 years: the REMEMBER pilot study.
        Menopause. 2006; 13: 28-36
        • MacLusky N.J.
        • Hajszan T.
        • Leranth C.
        The environmental estrogen bisphenol A inhibits estradiol-induced hippocampal synaptogenesis.
        Environ Health Perspect. 2005; 113: 675-679
        • Leranth C.
        • Hajszan T.
        • Szigeti-Buck K.
        • Bober J.
        • MacLusky N.J.
        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
        • Meeker J.D.
        • Calafat A.M.
        • 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
        • Stahlhut R.W.
        • van Wijngaarden E.
        • Dye T.D.
        • Cook S.
        • Swan S.H.
        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
        • Lang I.A.
        • Galloway T.S.
        • Scarlett A.
        • Henley W.E.
        • Depledge M.
        • Wallace R.B.
        • et al.
        Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults.
        JAMA. 2008; 300: 1303-1310
        • Bhasin S.
        • Cunningham G.R.
        • Hayes F.J.
        • Matsumoto A.M.
        • Snyder P.J.
        • Swerdloff R.S.
        • et al.
        Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline.
        J Clin Endocrinol Metab. 2010; 95: 2536-2559
        • Cahill L.
        Why sex matters for neuroscience.
        Nat Rev Neurosci. 2006; 7: 477-484