Maternal smoking and high BMI disrupt thyroid gland development

Panagiotis Filis; Sabine Hombach-Klonisch; Pierre Ayotte; Nalin Nagrath; Ugo Soffientini; Thomas Klonisch; Peter J. O'Shaughnessy; Paul A. Fowler

doi:10.1186/s12916-018-1183-7

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 language	English
Article number	194
Number of pages	15
Journal	BMC medicine
Volume	16
DOIs	https://doi.org/10.1186/s12916-018-1183-7
Publication status	Published - 23 Oct 2018

Bibliographical 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).

Keywords

fetus
human
thyroid
maternal smoking
maternal obesity
thyroid hormones
development

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12916-018-1183-7Licence: CC BY

Maternal smoking and high BMI disrupt thyroid gland development
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Final published version, 2.37 MBLicence: CC BY

Paul Alfred François Fowler
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Chair in Translational Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
Person: Academic

Cite this

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title = "Maternal smoking and high BMI disrupt thyroid gland development",

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. ",

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author = "Panagiotis Filis and Sabine Hombach-Klonisch and Pierre Ayotte and Nalin Nagrath and Ugo Soffientini and Thomas Klonisch and O'Shaughnessy, {Peter J.} and Fowler, {Paul A.}",

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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T1 - Maternal smoking and high BMI disrupt thyroid gland development

AU - Filis, Panagiotis

AU - Hombach-Klonisch, Sabine

AU - Ayotte, Pierre

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).

PY - 2018/10/23

Y1 - 2018/10/23

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.

AB - 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.

KW - fetus

KW - human

KW - thyroid

KW - maternal smoking

KW - maternal obesity

KW - thyroid hormones

KW - development

U2 - 10.1186/s12916-018-1183-7

DO - 10.1186/s12916-018-1183-7

M3 - Article

C2 - 30348172

SN - 1741-7015

VL - 16

JO - BMC medicine

JF - BMC medicine

M1 - 194

ER -

Maternal smoking and high BMI disrupt thyroid gland development

Abstract

Bibliographical note

Keywords

UN SDGs

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Paul Alfred François Fowler

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