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Cited by 25Thyroid Disorders and TreatmentsBirth, Development, and HealthEpigenetics and DNA Methylation

Maternal Exposure to Iodine Excess Throughout Pregnancy and Lactation Induces Hypothyroidism in Adult Male Rat Offspring

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Serrano-Nascimento, Caroline, Salgueiro, Rafael Barrera, Pantaleão, Thiago, Corrêa da Costa, Vânia Maria, Nunes, Maria Tereza·2017·Scientific Reports
DOI 10.1038/s41598-017-15529-9PMC PMC5688151
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Abstract

This study aimed to investigate the consequences of maternal exposure to iodine excess (IE; 0.6 mg NaI/L) throughout pregnancy and lactation on the hypothalamus-pituitary-thyroid axis of the male offspring in adulthood. Maternal IE exposure increased hypothalamic Trh mRNA expression and pituitary Tsh expression and secretion in the adult male offspring. Moreover, the IE-exposed offspring rats presented reduced thyroid hormones levels, morphological alterations in the thyroid follicles, increased thyroid oxidative stress and decreased expression of thyroid differentiation markers (Tshr, Nis, Tg, Tpo, Mct8) and thyroid transcription factors (Nkx2.1, Pax8). Finally, the data presented here strongly suggest that epigenetic mechanisms, as increased DNA methylation, augmented DNA methyltransferases expression, hypermethylation of histone H3, hypoaceylation of histones H3 and H4, increased expression/activity of histone deacetylases and decreased expression/activity of histone acetyltransferases are involved in the repression of thyroid gene expression in the adult male offspring. In conclusion, our results indicate that rat dams’ exposure to IE during pregnancy and lactation induces primary hypothyroidism and triggers several epigenetic changes in the thyroid gland of their male offspring in adulthood.

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  • Exposure to supraoptimal iodine levels during gestation and breastfeeding triggers adult-onset hypothyroidism in rat offspring, driven by epigenetic silencing-specifically, DNA hypermethylation and histone remodeling-of essential thyroid-regulating genes such as Tshr, Nis, Tpo, and Pax8.

    “Moreover, exposure to supraoptimal iodine levels during gestation and breastfeeding triggers adult-onset hypothyroidism in rat offspring. This condition is driven by epigenetic silencing—specifically, DNA hypermethylation and histone remodeling—of essential thyroid-regulating genes such as Tshr, Nis, Tpo, and Pax8.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [127]

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  • Both iodine deficiency and excess can result in long-term neurodevelopmental impairments and endocrine dysfunction through disrupted thyroid signaling and epigenetic mechanisms.

    “Both iodine deficiency and excess can result in long-term neurodevelopmental impairments and endocrine dysfunction through disrupted thyroid signaling and epigenetic mechanisms [119,126,127].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [127]

    The Introduction says iodine deficiency harms maternal thyroid function and fetal development, while the Discussion reports that maternal iodine excess caused hypothyroidism in adult male rat offspring and suggests epigenetic repression of thyroid genes. The paper does not establish long-term neurodevelopmental impairment from both deficiency and excess, or an epigenetic mechanism for deficiency; its adult findings concern iodine excess in male rats. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Serrano-Nascimento, C., Salgueiro, R. B., Pantaleão, T., Corrêa da Costa, V. M., & Nunes, M. T.
Affiliations
  • Universidade de São Paulo (BR)
  • Universidade Federal do Rio de Janeiro (BR)
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-11-15
Volume
7
Issue
1
Pages
15591-15591
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-15529-9
PMC
PMC5688151
OpenAlex
W2767499242
Cited by
25
References
3
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 1 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 1 · 2017: 1
FWCI
2.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (2012/24391-6, 13/05629-4)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (/2014-9)
  • Universidade de São Paulo
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
iodine excess, pregnancy, lactation, primary hypothyroidism, hypothalamic-pituitary-thyroid axis, thyroid gene expression, epigenetic regulation, DNA methylation, histone acetylation, histone deacetylase, histone acetyltransferase, male offspring
MeSH terms
Animals, Breast Feeding, Female, Humans, Hypothyroidism, Iodide Peroxidase, Iodine, Lactation, Pituitary Gland, Pregnancy, Thyroid Gland, Thyroid Hormones, Maternal Exposure, Rats

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