Maternal smoking and high BMI disrupt thyroid gland development

Panagiotis Filis (Corresponding Author), Sabine Hombach-Klonisch, Pierre Ayotte, Nalin Nagrath, Ugo Soffientini, Thomas Klonisch, Peter J. O'Shaughnessy, Paul A. Fowler

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Abstract

Background: Maternal lifestyle factors, including smoking and increased body weight, increase risks of adult diseases such as metabolic syndrome and infertility. The fetal thyroid gland is essential for the control of fetal metabolic rate, cardiac output and brain development. Altered fetal thyroid function may contribute to increased disease onset later in life. Here we investigated the impact of maternal smoking and high maternal weight on human fetal thyroid function during the 2nd trimester. Methods: Thyroid glands and plasma were collected from fetuses electively terminated in the 2nd trimester (normally progressing pregnancies). Plasma total triiodothyronine (T3) and total thyroxine (T4) were measured by solid-phase extraction-liquid chromatography tandem mass spectrometry. Fetal plasma thyroid stimulating hormone (TSH) levels were measured using a multiplex assay for Human Pituitary hormones. Histology and immunolocalization of thyroid developmental markers were examined in thyroid sections. Transcript levels of developmental, functional, apoptotic and detoxification markers were measured by real-time PCR. Statistical analyses were performed using multivariate linear regression models with fetal age, sex, and maternal smoking or maternal body mass index (BMI) as covariates. Results: Maternal smoking was associated with significant changes in fetal plasma T4 and TSH levels during the second trimester. Smoke-exposed thyroids had reduced thyroid GATA6 and NKX2-1 transcript levels and altered developmental trajectories for ESR2 and AHR transcript levels. Maternal BMI >25 was associated with increased fetal thyroid weight, increased plasma TSH levels and abnormal thyroid histology in female fetuses. Normal developmental changes in AHR and ESR1 transcript expression were also abolished in fetal thyroids from mothers with BMI >25. Conclusions: For the first time we show that maternal smoking and high maternal BMI are associated with disturbed fetal thyroid gland development and endocrine function in a sex-specific manner during the second trimester. These findings suggest that predisposition to post-natal disease is mediated, in part, by altered fetal thyroid gland development.
Original languageEnglish
Article number194
JournalBMC medicine
Volume16
DOIs
Publication statusPublished - 23 Oct 2018

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Thyroid Gland
Body Mass Index
Smoking
Mothers
Thyrotropin
Second Pregnancy Trimester
Thyroxine
Linear Models
Histology
Fetus
Fetal Weight
Pituitary Hormones
Solid Phase Extraction
Triiodothyronine
Tandem Mass Spectrometry
Smoke
Liquid Chromatography
Cardiac Output
Infertility
Gestational Age

Keywords

  • fetus
  • human
  • thyroid
  • maternal smoking
  • maternal obesity
  • thyroid hormones
  • development

Cite this

Filis, P., Hombach-Klonisch, S., Ayotte, P., Nagrath, N., Soffientini, U., Klonisch, T., ... Fowler , P. A. (2018). Maternal smoking and high BMI disrupt thyroid gland development. BMC medicine , 16, [194]. https://doi.org/10.1186/s12916-018-1183-7

Maternal smoking and high BMI disrupt thyroid gland development. / Filis, Panagiotis (Corresponding Author); Hombach-Klonisch, Sabine; Ayotte, Pierre; Nagrath, Nalin; Soffientini, Ugo; Klonisch, Thomas; O'Shaughnessy, Peter J.; Fowler , Paul A.

In: BMC medicine , Vol. 16, 194, 23.10.2018.

Research output: Contribution to journalArticle

Filis, P, Hombach-Klonisch, S, Ayotte, P, Nagrath, N, Soffientini, U, Klonisch, T, O'Shaughnessy, PJ & Fowler , PA 2018, 'Maternal smoking and high BMI disrupt thyroid gland development', BMC medicine , vol. 16, 194. https://doi.org/10.1186/s12916-018-1183-7
Filis P, Hombach-Klonisch S, Ayotte P, Nagrath N, Soffientini U, Klonisch T et al. Maternal smoking and high BMI disrupt thyroid gland development. BMC medicine . 2018 Oct 23;16. 194. https://doi.org/10.1186/s12916-018-1183-7
Filis, Panagiotis ; Hombach-Klonisch, Sabine ; Ayotte, Pierre ; Nagrath, Nalin ; Soffientini, Ugo ; Klonisch, Thomas ; O'Shaughnessy, Peter J. ; Fowler , Paul A. / Maternal smoking and high BMI disrupt thyroid gland development. In: BMC medicine . 2018 ; Vol. 16.
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note = "This study was supported by grants from the Medical Research Council (MR/L010011/1) (to PAF & PJOS), the Natural Science and Engineering Research Council of Canada (NSERC) for TK and SHK, and NHS Endowment Grant (to PF).",
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AU - Nagrath, Nalin

AU - Soffientini, Ugo

AU - Klonisch, Thomas

AU - O'Shaughnessy, Peter J.

AU - Fowler , Paul A.

N1 - This study was supported by grants from the Medical Research Council (MR/L010011/1) (to PAF & PJOS), the Natural Science and Engineering Research Council of Canada (NSERC) for TK and SHK, and NHS Endowment Grant (to PF).

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N2 - Background: Maternal lifestyle factors, including smoking and increased body weight, increase risks of adult diseases such as metabolic syndrome and infertility. The fetal thyroid gland is essential for the control of fetal metabolic rate, cardiac output and brain development. Altered fetal thyroid function may contribute to increased disease onset later in life. Here we investigated the impact of maternal smoking and high maternal weight on human fetal thyroid function during the 2nd trimester. Methods: Thyroid glands and plasma were collected from fetuses electively terminated in the 2nd trimester (normally progressing pregnancies). Plasma total triiodothyronine (T3) and total thyroxine (T4) were measured by solid-phase extraction-liquid chromatography tandem mass spectrometry. Fetal plasma thyroid stimulating hormone (TSH) levels were measured using a multiplex assay for Human Pituitary hormones. Histology and immunolocalization of thyroid developmental markers were examined in thyroid sections. Transcript levels of developmental, functional, apoptotic and detoxification markers were measured by real-time PCR. Statistical analyses were performed using multivariate linear regression models with fetal age, sex, and maternal smoking or maternal body mass index (BMI) as covariates. Results: Maternal smoking was associated with significant changes in fetal plasma T4 and TSH levels during the second trimester. Smoke-exposed thyroids had reduced thyroid GATA6 and NKX2-1 transcript levels and altered developmental trajectories for ESR2 and AHR transcript levels. Maternal BMI >25 was associated with increased fetal thyroid weight, increased plasma TSH levels and abnormal thyroid histology in female fetuses. Normal developmental changes in AHR and ESR1 transcript expression were also abolished in fetal thyroids from mothers with BMI >25. Conclusions: For the first time we show that maternal smoking and high maternal BMI are associated with disturbed fetal thyroid gland development and endocrine function in a sex-specific manner during the second trimester. These findings suggest that predisposition to post-natal disease is mediated, in part, by altered fetal thyroid gland development.

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