Evaluating Thyroid Disrupting Chemicals In Vivo Using Xenopus laevis

  • Bilal B. Mughal
  • Barbara A. Demeneix
  • Jean-Baptiste Fini
Part of the Methods in Molecular Biology book series (MIMB, volume 1801)


Using in vivo animal model systems for chemical screening can permit evaluation of the signaling pathways implicated. Xenopus laevis is an ideal model organism to test thyroid axis disruption as thyroid hormones are highly conserved across vertebrates. Here, we describe a high-throughput assay using non-feeding embryonic stage transgenic X. laevis (TH/bZip) to screen for thyroid disrupting chemicals using a 3 day exposure protocol. We further describe a protocol to detect endocrine disruption of thyroid axis by the analysis of gene expression using wild-type X. laevis.

Key words

Xenopus laevis Thyroid signaling Endocrine disruption Thyroid disruption XETA assay Neurodevelopment Gene expression Behavior analysis 



We thank Gérard Benisti, Philippe Durand and Jean-Paul Chaumeil for excellent animal care and thank Sébastien Le Mével for his input in the methods which are routinely used. This protocol has been refined thanks to work supported by grants from Centre National de la Recherche Scientifique (CNRS), Muséum National d’Histoire Naturelle (MNHN), and from European Union DevCom FP7-People-2013-ITN N°607142.


  1. 1.
    Delange F (1989) Iodine nutrition and congenital hypothyroidism. In: Research in congenital hypothyroidism. Springer US, Boston, MA, pp 173–185CrossRefGoogle Scholar
  2. 2.
    Gaitan E, Lindsay RH, Reichert RD et al (1989) Antithyroid and goitrogenic effects of millet: role of C-glycosylflavones. J Clin Endocrinol Metab 68:707–714CrossRefPubMedGoogle Scholar
  3. 3.
    Pop VJ, De Vries E, Van Baar AL et al (1995) Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development? J Clin Endocrinol Metab 80:3561–3566CrossRefPubMedGoogle Scholar
  4. 4.
    Pop VJ, Brouwers EP, Vader HL et al (2003) Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol 59:282–288CrossRefGoogle Scholar
  5. 5.
    Kooistra L (2006) Neonatal effects of maternal Hypothyroxinemia during early pregnancy. Pediatrics 117:161–167CrossRefPubMedGoogle Scholar
  6. 6.
    Henrichs J, Bongers-Schokking JJ, Schenk JJ et al (2010) Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metabol 95:4227–4234CrossRefGoogle Scholar
  7. 7.
    Costeira MJ, Oliveira P, Santos NC et al (2011) Psychomotor development of children from an iodine-deficient region. J Pediatr 159:447–453CrossRefPubMedGoogle Scholar
  8. 8.
    Finken MJJ, Van Eijsden M, Loomans EM et al (2013) Maternal hypothyroxinemia in early pregnancy predicts reduced performance in reaction time tests in 5- to 6-year-old offspring. J Clin Endocrinol Metab 98:1417–1426CrossRefPubMedGoogle Scholar
  9. 9.
    Julvez J, Alvarez-Pedrerol M, Rebagliato M et al (2013) Thyroxine levels during pregnancy in healthy women and early child neurodevelopment. Epidemiology 24:150–157CrossRefPubMedGoogle Scholar
  10. 10.
    Ghassabian A, El Marroun H, Peeters RP et al (2014) Downstream effects of maternal hypothyroxinemia in early pregnancy: nonverbal IQ and brain morphology in school-age children. J Clin Endocrinol Metab 99:2383–2390CrossRefPubMedGoogle Scholar
  11. 11.
    Korevaar TIM, Muetzel R, Medici M et al (2016) 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 4:35–43CrossRefPubMedGoogle Scholar
  12. 12.
    Fini JB, Le Mevel S, Turque N et al (2007) An in vivo multiwell-based fluorescent screen for monitoring vertebrate thyroid hormone disruption. Environ Sci Technol 41:5908–5914CrossRefPubMedGoogle Scholar
  13. 13.
    Nieuwkoop PD, Faber J (1994) Normal table of Xenopus laevis (Daudin): a systematical & chronological survey of the development from the fertilized egg till the end of metamorphosis Garland Science, 1994 2. ed. Amsterdam : North-Holland Pub. Co., 1967. ISBN 10: 0815318960 ISBN 13: 9780815318965Google Scholar
  14. 14.
    Fini JB, Riu A, Debrauwer L et al (2012) Parallel biotransformation of tetrabromobisphenol A in Xenopus laevis and mammals: Xenopus as a model for endocrine perturbation studies. Toxicol Sci. 125(2):359–67CrossRefPubMedGoogle Scholar
  15. 15.
    Fini J-B, Mughal BB, Le Mével S et al (2017) Human amniotic fluid contaminants alter thyroid hormone signaling and early brain development in Xenopus embryos. Sci Rep 7:43786CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Bilal B. Mughal
    • 1
  • Barbara A. Demeneix
    • 1
  • Jean-Baptiste Fini
    • 1
  1. 1.Evolution des Régulations Endocriniennes, Département “Adaptation du Vivant”UMR 7221 Muséum National d’Histoire Naturelle /CNRSParisFrance

Personalised recommendations