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Review

Impact of endocrine disrupting chemicals on neurodevelopment: the need for better testing strategies for endocrine disruption-induced developmental neurotoxicity

, , , , &
Pages 131-141 | Received 09 Dec 2021, Accepted 17 Feb 2022, Published online: 07 Mar 2022

References

  • Schug TT, Blawas AM, Gray K, et al. Elucidating the links between endocrine disruptors and neurodevelopment. Endocrinology. 2015;156(6):1941–1951.
  • Jansen TA, Korevaar TIM, Mulder TA, et al. Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort. Lancet Diabetes Endocrinol. 2019;7(8):629–637.
  • Iturbide A, Ruiz Tejeda Segura ML, Noll C, et al. Retinoic acid signaling is critical during the totipotency window in early mammalian development. Nat Struct Mol Biol. 2021;28(6):521–532.
  • Giannocco G, Kizys MML, Maciel RM, et al. Thyroid hormone, gene expression, and central nervous system: where we are. Semin Cell Dev Biol. 2021;114:47–56.
  • Chatonnet F, Guyot R, Benoît G, et al. Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells. Proc Natl Acad Sci U S A. 2013;110(8):E766–75.
  • International Programme on Chemical Safety, World Health Organization.Global assessment on the state of the science of endocrine disruptors; 2002. Retrieved 2022 03 03. https://apps.who.int/iris/handle/10665/67357
  • Woodruff TJ, Zota AR, Schwartz JM. Environmental chemicals in pregnant women in the United States: NHANES 2003–2004. Environ Health Perspect. 2011;119(119.6):878–885.
  • Derakhshan A, Shu H, Broeren MAC, et al. Association of phthalate exposure with thyroid function during pregnancy. Environ Int. 2021;157:106795.
  • Rivollier F, Krebs MO, Kebir O. Perinatal exposure to environmental endocrine disruptors in the emergence of neurodevelopmental psychiatric diseases: a systematic review. Int J Environ Res Public Health. 2019;16(8):1318.
  • Stein TP, Schluter MD, Steer RA, et al. Bisphenol a exposure in children with autism spectrum disorders. Autism Res. 2015;8(3):272–283.
  • Lim YH, Bae S, Kim BN, et al. Prenatal and postnatal bisphenol A exposure and social impairment in 4-year-old children. Environ Health. 2017;16(1):79.
  • Braun JM, Muckle G, Arbuckle T, et al. Associations of prenatal urinary bisphenol a concentrations with child behaviors and cognitive abilities. Environ Health Perspect. 2017;125(6):067008.
  • Hansen JB, Bilenberg N, Timmermann CAG, et al. Prenatal exposure to bisphenol A and autistic- and ADHD-related symptoms in children aged 2 and5 years from the odense child cohort. Environ Health. 2021;20(1):24.
  • Oulhote Y, Lanphear B, Braun JM, et al. Gestational exposures to phthalates and folic acid, and autistic traits in canadian children. Environ Health Perspect. 2020;128(2):27004.
  • Alampi JD, Lanphear BP, Braun JM, et al. Association between gestational exposure to toxicants and autistic behaviors using bayesian quantile regression. Am J Epidemiol. 2021;190(9):1803–1813.
  • Shin HM, Bennett DH, Calafat AM, et al. Modeled prenatal exposure to per- and polyfluoroalkyl substances in association with child autism spectrum disorder: a case-control study. Environ Res. 2020;186:109514.
  • Oh J, Bennett DH, Calafat AM, et al. Prenatal exposure to per- and polyfluoroalkyl substances in association with autism spectrum disorder in the MARBLES study. Environ Int. 2021;147:106328.
  • Arbuckle TE, Davis K, Boylan K, et al. Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian children 6–11 years of age: CHMS 2007–2009. Neurotoxicology. 2016;54:89–98.
  • England-Mason G, Martin JW, MacDonald A, et al. Similar names, different results: consistency of the associations between prenatal exposure to phthalates and parent-ratings of behavior problems in preschool children. Environ Int. 2020;142:105892.
  • Ku HY, Tsai TL, Wang PL, et al. Prenatal and childhood phthalate exposure and attention deficit hyperactivity disorder traits in child temperament: a 12-year follow-up birth cohort study. Sci Total Environ. 2020;699:134053.
  • Lenters V, Iszatt N, Forns J, et al. Early-life exposure to persistent organic pollutants (OCPs, PBDEs, PCBs, PFASs) and attention-deficit/hyperactivity disorder: a multi-pollutant analysis of a Norwegian birth cohort. Environ Int. 2019;125:33–42.
  • Jankowska A, Polańska K, Koch HM, et al. Phthalate exposure and neurodevelopmental outcomes in early school age children from Poland. Environ Res. 2019;179(Pt B):108829.
  • Bornehag CG, Engdahl E, Unenge Hallerbäck M, et al. Prenatal exposure to bisphenols and cognitive function in children at 7 years of age in the Swedish SELMA study. Environ Int. 2021;150:106433.
  • Tanner EM, Hallerbäck MU, Wikström S, et al. Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven. Environ Int. 2020;134:105185.
  • Guo J, Wu C, Zhang J, et al. Prenatal exposure to mixture of heavy metals, pesticides and phenols and IQ in children at 7 years of age: the SMBCS study. Environ Int. 2020;139:105692.
  • England-Mason G, Liu J, Martin JW, et al. Postnatal BPA is associated with increasing executive function difficulties in preschool children. Pediatr Res. 2021;89(3):686–693.
  • Pan R, Wang C, Shi R, et al. Prenatal Bisphenol A exposure and early childhood neurodevelopment in Shandong, China. Int J Hyg Environ Health. 2019;222(5):896–902.
  • Minatoya M, Araki A, Nakajima S, et al. Cord blood BPA level and child neurodevelopment and behavioral problems: the hokkaido study on environment and children’s health. Sci Total Environ. 2017;607–608:351–356.
  • Li N, Papandonatos GD, Calafat AM, et al. Gestational and childhood exposure to phthalates and child behavior. Environ Int. 2020;144:106036.
  • Jackson-Browne MS, Papandonatos GD, Chen A, et al. Gestational and childhood urinary triclosan concentrations and academic achievement among 8-year-old children. Neurotoxicology. 2020;78:170–176.
  • Dingemans MM, van den Berg M, Westerink RH. Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system. Environ Health Perspect. 2011;119(7):900–907.
  • Quinnies KM, Harris EP, Snyder RW, et al. Direct and transgenerational effects of low doses of perinatal di-(2-ethylhexyl) phthalate (DEHP) on social behaviors in mice. PLoS One. 2017;12(2):e0171977.
  • Xu XH, Zhang J, Wang YM, et al. Perinatal exposure to bisphenol-A impairs learning-memory by concomitant down-regulation of N-methyl-D-aspartate receptors of hippocampus in male offspring mice. Horm Behav. 2010;58(2):326–333.
  • André SM, Markowski VP. Learning deficits expressed as delayed extinction of a conditioned running response following perinatal exposure to vinclozolin. Neurotoxicol Teratol. 2006;28(4):482–488.
  • Nalvarte I, Varshney M, Inzunza J, et al. Estrogen receptor beta and neural development. Vitam Horm. 2021;116:313–326.
  • Küppers E, Ivanova T, Karolczak M, et al. Classical and nonclassical estrogen action in the developing midbrain. Horm Behav. 2001;40(2):196–202.
  • Rovet JF. The role of thyroid hormones for brain development and cognitive function. Endocr Dev. 2014;26:26–43.
  • Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341(8):549–555.
  • Andersen SL, Andersen S, Vestergaard P, et al. Maternal thyroid function in early pregnancy and child neurodevelopmental disorders: a danish nationwide case-cohort study. Thyroid. 2018;28(4):537–546.
  • Getahun D, Jacobsen SJ, Fassett MJ, et al. Association between maternal hypothyroidism and autism spectrum disorders in children. Pediatr Res. 2018;83(3):580–588.
  • Korevaar TI, Muetzel R, Medici M, et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol. 2016;4(1):35–43.
  • Remaud S, Ortiz FC, and Perret-Jeanneret M, et al. Transient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain. Elife. 2017;6:e29996.
  • López-Juárez A, Remaud S, Hassani Z, et al. Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche. Cell Stem Cell. 2012;10(5):531–543.
  • Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012;122(9):3035–3043.
  • Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 1996;379(6564):458–460.
  • Riedel C, Levy O, Carrasco N. Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin. J Biol Chem. 2001;276(24):21458–21463.
  • Kogai T, Curcio F, Hyman S, et al. Induction of follicle formation in long-term cultured normal human thyroid cells treated with thyrotropin stimulates iodide uptake but not sodium/iodide symporter messenger RNA and protein expression. J Endocrinol. 2000;167(1):125–135.
  • Wolff J. Congenital goiter with defective iodide transport. Endocr Rev. 1983;4(3):240–254.
  • Yoshida A, Taniguchi S, Hisatome I, et al. Pendrin is an iodide-specific apical porter responsible for iodide efflux from thyroid cells. J Clin Endocrinol Metab. 2002;87(7):3356–3361.
  • Gillam MP, Sidhaye AR, Lee EJ, et al. Functional characterization of pendrin in a polarized cell system. Evidence for pendrin-mediated apical iodide efflux. J Biol Chem. 2004;279(13):13004–13010.
  • Ohara A, Yamada F, Fukuda T, et al. Specific alteration of gene expression profile in rats by treatment with thyroid toxicants that inhibit thyroid hormone synthesis. J Appl Toxicol. 2018;38(12):1529–1537.
  • Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18(3):404–433.
  • Vella KR, Hollenberg AN. The actions of thyroid hormone signaling in the nucleus. Mol Cell Endocrinol. 2017;458:127–135.
  • Jones I, Srinivas M, Ng L, et al. The thyroid hormone receptor beta gene: structure and functions in the brain and sensory systems. Thyroid. 2003;13(11):1057–1068.
  • Flamant F, Gauthier K, Richard S. genetic investigation of thyroid hormone receptor function in the developing and adult brain. Curr Top Dev Biol. 2017;125:303–335.
  • Bochukova E, Schoenmakers N, Agostini M, et al. A mutation in the thyroid hormone receptor alpha gene. N Engl J Med. 2012;366(3):243–249.
  • Dumitrescu AM, Refetoff S. The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta. 2013;1830(7):3987–4003.
  • Davis PJ, Goglia F, Leonard JL. Nongenomic actions of thyroid hormone. Nat Rev Endocrinol. 2016;12(2):111–121.
  • Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010;31(2):139–170.
  • Bernal J. The significance of thyroid hormone transporters in the brain. Endocrinology. 2005;146(4):1698–1700.
  • Fischer J, Kleinau G, Müller A, et al. Modulation of monocarboxylate transporter 8 oligomerization by specific pathogenic mutations. J Mol Endocrinol. 2015;54(1):39–50.
  • Fernández LP, López-Márquez A, Santisteban P. Thyroid transcription factors in development, differentiation and disease. Nat Rev Endocrinol. 2015;11(1):29–42.
  • Patel J, Landers K, Li H, et al. Delivery of maternal thyroid hormones to the fetus. Trends Endocrinol Metab. 2011;22(5):164–170.
  • McKinnon B, Li H, Richard K, et al. Synthesis of thyroid hormone binding proteins transthyretin and albumin by human trophoblast. J Clin Endocrinol Metab. 2005;90(12):6714–6720.
  • Koopdonk-Kool JM, de Vijlder JJ, Veenboer GJ, et al. Type II and type III deiodinase activity in human placenta as a function of gestational age. J Clin Endocrinol Metab. 1996;81(6):2154–2158.
  • Schiera G, Di Liegro CM, Di Liegro I. Involvement of thyroid hormones in brain development and cancer. Cancers (Basel). 2021;13(11). DOI:https://doi.org/10.3390/cancers13112693
  • Morte B, Bernal J. Thyroid hormone action: astrocyte-neuron communication. Front Endocrinol (Lausanne). 2014;5:82.
  • Fliers E, Unmehopa UA, Alkemade A. Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland. Mol Cell Endocrinol. 2006;251(1–2):1–8.
  • Chan SY, Franklyn JA, Pemberton HN, et al. Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction. J Endocrinol. 2006;189(3):465–471.
  • Sato K, Sugawara J, Sato T, et al. Expression of organic anion transporting polypeptide E (OATP-E) in human placenta. Placenta. 2003;24(2–3):144–148.
  • Decherf S, Seugnet I, Fini JB, et al. Disruption of thyroid hormone-dependent hypothalamic set-points by environmental contaminants. Mol Cell Endocrinol. 2010;323(2):172–182.
  • Tonacchera M, Pinchera A, Dimida A, et al. Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. Thyroid. 2004;14(12):1012–1019.
  • Lisco G, De Tullio A, Giagulli VA, et al. Interference on iodine uptake and human thyroid function by perchlorate-contaminated water and food. Nutrients. 2020;12(6):1669.
  • Niziński P, Błażewicz A, Kończyk J, et al. Perchlorate - properties, toxicity and human health effects: an updated review. Rev Environ Health. 2020;36(2):199–222.
  • Taylor PN, Okosieme OE, Murphy R, et al. Maternal perchlorate levels in women with borderline thyroid function during pregnancy and the cognitive development of their offspring: data from the controlled antenatal thyroid study. J Clin Endocrinol Metab. 2014;99(11):4291–4298.
  • Gilbert ME, Sui L. Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat. Environ Health Perspect. 2008;116(6):752–760.
  • Leemans M, Couderq S, Demeneix B, et al. Pesticides with potential thyroid hormone-disrupting effects: a review of recent data. Front Endocrinol (Lausanne). 2019;10:743.
  • Ghassabian A, Trasande L. Disruption in thyroid signaling pathway: a mechanism for the effect of endocrine-disrupting chemicals on child neurodevelopment. Front Endocrinol (Lausanne). 2018;9:204.
  • Naveau E, Pinson A, Gérard A, et al. Alteration of rat fetal cerebral cortex development after prenatal exposure to polychlorinated biphenyls. PLoS One. 2014;9(3):e91903.
  • Ramírez V, Gálvez-Ontiveros Y, González-Domenech PJ, et al. Role of endocrine disrupting chemicals in children’s neurodevelopment. Environ Res. 2022;203:111890.
  • Zhang X, Qi W, Xu Q, et al. Di(2-ethylhexyl) phthalate (DEHP) and thyroid: biological mechanisms of interference and possible clinical implications. Environ Sci Pollut Res Int. 2022;29(2):1634–1644.
  • Polanska K, Ligocka D, Sobala W, et al. Phthalate exposure and child development: the polish mother and child cohort study. Early Hum Dev. 2014;90(9):477–485.
  • Kim Y, Ha EH, Kim EJ, et al. Prenatal exposure to phthalates and infant development at 6 months: prospective mothers and children’s environmental health (MOCEH) study. Environ Health Perspect. 2011;119(10):1495–1500.
  • Bornehag CG, Lindh C, Reichenberg A, et al. Association of prenatal phthalate exposure with language development in early childhood. JAMA Pediatr. 2018;172(12):1169–1176.
  • Aung MT, Johns LE, Ferguson KK, et al. Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: a repeated measures study. Environ Int. 2017;104:33–40.
  • Romano ME, Webster GM, Vuong AM, et al. Gestational urinary bisphenol A and maternal and newborn thyroid hormone concentrations: the home study. Environ Res. 2015;138:453–460.
  • Palanza P, Paterlini S, Brambilla MM, et al. Sex-biased impact of endocrine disrupting chemicals on behavioral development and vulnerability to disease: of mice and children. Neurosci Biobehav Rev. 2021;121:29–46.
  • Niederreither K, Dollé P. Retinoic acid in development: towards an integrated view. Nat Rev Genet. 2008;9(7):541–553.
  • McCaffery PJ, Adams J, Maden M, et al. Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen. Eur J Neurosci. 2003;18(3):457–472.
  • Kawaguchi R, Yu J, Honda J, et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science. 2007;315(5813):820–825.
  • Kedishvili NY. retinoic acid synthesis and degradation. Subcell Biochem. 2016;81:127–161.
  • Haeseleer F, Huang J, Lebioda L, et al. Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal. J Biol Chem. 1998;273(34):21790–21799.
  • Fujii H,Sato T., Kaneko S., et al. Metabolic inactivation of retinoic acid by a novel P450 differentially expressed in developing mouse embryos. The EMBO Journal. 1997;16(14):4163–4173.
  • Strate I, Min TH, Iliev D, et al. Retinol dehydrogenase 10 is a feedback regulator of retinoic acid signalling during axis formation and patterning of the central nervous system. Development. 2009;136(3):461–472.
  • Niederreither K, McCaffery P, Dräger UC, et al. Restricted expression and retinoic acid-induced downregulation of the retinaldehyde dehydrogenase type 2 (RALDH-2) gene during mouse development. Mech Dev. 1997;62(1):67–78.
  • White RJ, Nie Q, Lander AD, et al. Complex regulation of cyp26a1 creates a robust retinoic acid gradient in the zebrafish embryo. PLoS Biol. 2007;5(11):e304.
  • Mangelsdorf DJ. Vitamin A receptors. Nutr Rev. 1994;52(2 Pt 2):S32–44.
  • Umesono K, Evans RM. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell. 1989;57(7):1139–1146.
  • Janowski BA, Grogan MJ, Jones SA, et al. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci U S A. 1999;96(1):266–271.
  • Dollé P. Developmental expression of retinoic acid receptors (RARs). Nucl Recept Signal. 2009;7:e006.
  • Diez Del Corral R, Olivera-Martinez I, Goriely A, et al. Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension. Neuron. 2003;40(1):65–79.
  • Diez Del Corral R, Storey KG. Opposing FGF and retinoid pathways: a signalling switch that controls differentiation and patterning onset in the extending vertebrate body axis. Bioessays. 2004;26(8):857–869.
  • Niederreither K, Subbarayan V, Dollé P, et al. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat Genet. 1999;21(4):444–448.
  • Ribes V, Le Roux I, Rhinn M, et al. Early mouse caudal development relies on crosstalk between retinoic acid, Shh and Fgf signalling pathways. Development. 2009;136(4):665–676.
  • Shiotsugu J, Katsuyama Y, Arima K, et al. Multiple points of interaction between retinoic acid and FGF signaling during embryonic axis formation. Development. 2004;131(11):2653–2667.
  • Hernandez RE, Putzke AP, Myers JP, et al. Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development. Development. 2007;134(1):177–187.
  • Ribes V, Fraulob V, Petkovich M, et al. The oxidizing enzyme CYP26a1 tightly regulates the availability of retinoic acid in the gastrulating mouse embryo to ensure proper head development and vasculogenesis. Dev Dyn. 2007;236(3):644–653.
  • Uehara M, Yashiro K, Mamiya S, et al. CYP26A1 and CYP26C1 cooperatively regulate anterior-posterior patterning of the developing brain and the production of migratory cranial neural crest cells in the mouse. Dev Biol. 2007;302(2):399–411.
  • Williams AL, Bohnsack BL. What’s retinoic acid got to do with it? Retinoic acid regulation of the neural crest in craniofacial and ocular development. Genesis. 2019;57(7–8):e23308.
  • Mollard R, Viville S, Ward SJ, et al. Tissue-specific expression of retinoic acid receptor isoform transcripts in the mouse embryo. Mech Dev. 2000;94(1–2):223–232.
  • Ruberte E, Friederich V, Chambon P, et al. Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Development. 1993;118(1):267–282.
  • Kurosaka H, Wang Q, Sandell L, et al. Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia. Hum Mol Genet. 2017;26(7):1268–1279.
  • Sandell LL, Sanderson BW, Moiseyev G, et al. RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development. Genes Dev. 2007;21(9):1113–1124.
  • Niederreither K, Vermot J, Schuhbaur B, et al. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Development. 2002;129(15):3563–3574.
  • Dupé V, Matt N, Garnier JM, et al. A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment. Proc Natl Acad Sci U S A. 2003;100(24):14036–14041.
  • Abu-Abed S, Dollé P, Metzger D, et al. The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures. Genes Dev. 2001;15(2):226–240.
  • Yashiro K, Zhao X, Uehara M, et al. Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb. Dev Cell. 2004;6(3):411–422.
  • Gagné AM, Hébert M, Maziade M. Revisiting visual dysfunctions in schizophrenia from the retina to the cortical cells: a manifestation of defective neurodevelopment. Prog Neuropsychopharmacol Biol Psychiatry. 2015;62:29–34.
  • Mw HEB, McCollum EV, McCollum EV. Further studies on the nutritive deficiencies of wheat and grain mixtures and the pathological conditions produced in swine by their use. J Biol Chem. 1916;25(2):239–259.
  • Hughes HJS, Lienhardt HF, Aubel CE. Nerve degeneration resulting from avitaminosis A. J Nutr. 1929;2(2):183–186.
  • Corcoran J, So PL, Barber RD, et al. Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro. J Cell Sci. 2002;115(Pt 19):3779–3786.
  • Hale F. Pigs Born without Eye Balls. In: Persaud T. V. N., editors. Problems of Birth Defects. Dordrecht: Springer; 1993. p. 166–167.
  • Maden M, Gale E, Kostetskii I, et al. Vitamin A-deficient quail embryos have half a hindbrain and other neural defects. Curr Biol. 1996;6(4):417–426.
  • White JC, Highland M, Kaiser M, et al. Vitamin A deficiency results in the dose-dependent acquisition of anterior character and shortening of the caudal hindbrain of the rat embryo. Dev Biol. 2000;220(2):263–284.
  • Dupé V, Lumsden A. Hindbrain patterning involves graded responses to retinoic acid signalling. Development. 2001;128(12):2199–2208.
  • Wendling O, Ghyselinck NB, Chambon P, et al. Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterning. Development. 2001;128(11):2031–2038.
  • Niederreither K, Vermot J, Schuhbaur B, et al. Retinoic acid synthesis and hindbrain patterning in the mouse embryo. Development. 2000;127(1):75–85.
  • Bao Y, Ibram G, Blaner WS, et al. Low maternal retinol as a risk factor for schizophrenia in adult offspring. Schizophr Res. 2012;137(1–3):159–165.
  • Rohde CM, Manatt M, Clagett-Dame M, et al. Vitamin A antagonizes the action of vitamin D in rats. J Nutr. 1999;129(12):2246–2250.
  • McGrath JJ, Eyles DW, Pedersen CB, et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry. 2010;67(9):889–894.
  • Valipour G, Saneei P, Esmaillzadeh A. Serum vitamin D levels in relation to schizophrenia: a systematic review and meta-analysis of observational studies. J Clin Endocrinol Metab. 2014;99(10):3863–3872.
  • Cohlan SQ. Excessive intake of vitamin A as a cause of congenital anomalies in the rat. Science. 1953;117(3046):535–536.
  • Kochhar DM. Teratogenic activity of retinoic acid. Acta Pathol Microbiol Scand. 1967;70(3):398–404.
  • Giguere V, Ong ES, Segui P, et al. Identification of a receptor for the morphogen retinoic acid. Nature. 1987;330(6149):624–629.
  • Petkovich M, Brand NJ, Krust A, et al. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987;330(6147):444–450.
  • Shenefelt RE. Morphogenesis of malformations in hamsters caused by retinoic acid: relation to dose and stage at treatment. Teratology. 1972;5(1):103–118.
  • Lohnes D, Mark M, Mendelsohn C, et al. Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. Development. 1994;120(10):2723–2748.
  • Mallo M. Retinoic acid disturbs mouse middle ear development in a stage-dependent fashion. Dev Biol. 1997;184(1):175–186.
  • Hendrickx AG, Tzimas G, Korte R, et al. Retinoid teratogenicity in the macaque: verification of dosing regimen. J Med Primatol. 1998;27(6):310–318.
  • Sockanathan S, Jessell TM. Motor neuron-derived retinoid signaling specifies the subtype identity of spinal motor neurons. Cell. 1998;94(4):503–514.
  • Adams J, Lammer E.J. Human isotretinoin exposure: the teratogenesis of a syndrome of cognitive deficits Neurotoxicology and Teratology. 1995;3(17):386.
  • Adams JBS, Gavin JA, Janulewicz PA, et al. Neuropsychological characteristics of children embryonically exposed to isotretinoin (Accutane®): outcome at age 10. Neurotoxicol Teratol. 2001;23:296.
  • Adams Jane, Holson, R. Robert. The Neurobehavioral Teratology of Vitamin A Analogs. In Slikker Jr, William, Paule Merle G, Wang, Cheng, editors. Handbook of Developmental Neurotoxicology. 1998;631–642.
  • Petrelli B, Bendelac L, Hicks GG, et al. Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder. Genesis. 2019;57(1):e23278.
  • Satiroglu-Tufan NL, Tufan AC. Amelioration of ethanol-induced growth retardation by all-trans-retinoic acid and alpha-tocopherol in shell-less culture of the chick embryo. Reprod Toxicol. 2004;18(3):407–412.
  • Twal WO, Zile MH. Retinoic acid reverses ethanol-induced cardiovascular abnormalities in quail embryos. Alcohol Clin Exp Res. 1997;21(6):1137–1143.
  • Marrs JA, Clendenon SG, Ratcliffe DR, et al. Zebrafish fetal alcohol syndrome model: effects of ethanol are rescued by retinoic acid supplement. Alcohol. 2010;44(7–8):707–715.
  • Romoli M, Mazzocchetti P, D’Alonzo R, et al. Valproic Acid and Epilepsy: from Molecular Mechanisms to Clinical Evidences. Curr Neuropharmacol. 2019;17(10):926–946.
  • Nau H, Hauck RS, Ehlers K. Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Toxicol Pharmacol. 1991;69(5):310–321.
  • Kultima K, Jergil M, Salter H, et al. Early transcriptional responses in mouse embryos as a basis for selection of molecular markers predictive of valproic acid teratogenicity. Reprod Toxicol. 2010;30(3):457–468.
  • Jergil M, Kultima K, Gustafson AL, et al. Valproic acid-induced deregulation in vitro of genes associated in vivo with neural tube defects. Toxicol Sci. 2009;108(1):132–148.
  • Piersma AH, Hessel EV, Staal YC. Retinoic acid in developmental toxicology: teratogen, morphogen and biomarker. Reprod Toxicol. 2017;72:53–61.
  • Li AS, Marikawa Y. Adverse effect of valproic acid on an in vitro gastrulation model entails activation of retinoic acid signaling. Reprod Toxicol. 2016;66:68–83.
  • Xiong B, Loss RD, Shields D, et al. Polyacrylamide degradation and its implications in environmental systems. Npj Clean Water. 2018;1(1):17.
  • Lindeman B, Johansson Y, Andreassen M, et al. Does the food processing contaminant acrylamide cause developmental neurotoxicity? A review and identification of knowledge gaps. Reprod Toxicol. 2021;101:93–114.
  • Attoff K, Johansson Y, Cediel-Ulloa A, et al. Acrylamide alters CREB and retinoic acid signalling pathways during differentiation of the human neuroblastoma SH-SY5Y cell line. Sci Rep. 2020;10(1):16714.
  • Fritsche E,Crofton K.M, Hernandez A.F, et al. OECD/EFSA workshop on developmental neurotoxicity (DNT): the use of non-animal test methods for regulatory purposes. Altex. 2017;34(2):311–315.
  • Sachana M, Bal-Price A, Crofton KM, et al. International regulatory and scientific effort for improved developmental neurotoxicity testing. Toxicol Sci. 2019;167(1):45–57.
  • Fritsche E, Grandjean P, Crofton KM, et al. Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes. Toxicol Appl Pharmacol. 2018;354:3–6.
  • Krebs A, van Vugt-lussenburg BMA, Waldmann T, et al. The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods. Arch Toxicol. 2020;94(7):2435–2461.
  • Bal-Price A,Hogberg H.T, Crofton K.M, et al. Recommendation on test readiness criteria for new approach methods in toxicology: exemplified for developmental neurotoxicity. Altex. 2018;35(3):306–352.
  • OECD. Guidance Document for the Use of Adverse Outcome Pathways in Developing Integrated Approaches to Testing and Assessment (IATA) 2017.
  • Lupu D, Andersson P, Bornehag CG, et al. The endpoints project: novel testing strategies for endocrine disruptors linked to developmental neurotoxicity. Int J Mol Sci. 2020;21(11):3978.
  • Kortenkamp A, Axelstad M, Baig AH, et al. Removing critical gaps in chemical test methods by developing new assays for the identification of thyroid hormone system-disrupting chemicals-the athena project. Int J Mol Sci. 2020;21(9):3123.
  • Holbech H, Matthiessen P, Hansen M, et al. Ergo: breaking down the wall between human health and environmental testing of endocrine disrupters. Int J Mol Sci. 2020;21(8):2954.
  • Moroni L, Barbaro F, Caiment F, et al. Screened: a multistage model of thyroid gland function for screening endocrine-disrupting chemicals in a biologically sex-specific manner. Int J Mol Sci. 2020;21(10):3648.
  • Commission E, Environment D-Gf, Ramhøj L, Martin O, Axelstad M, et al. Development of a study protocol for thyroid disruptor testing in the mammalian system: deliverable 16: final feasibility study report: Publications Office; 2019.