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...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | BMC Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12916-018-1183-7 |
| _version_ | 1819069388878249984 |
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| author | Panagiotis Filis Sabine Hombach-Klonisch Pierre Ayotte Nalin Nagrath Ugo Soffientini Thomas Klonisch Peter O’Shaughnessy Paul A. Fowler |
| author_facet | Panagiotis Filis Sabine Hombach-Klonisch Pierre Ayotte Nalin Nagrath Ugo Soffientini Thomas Klonisch Peter O’Shaughnessy Paul A. Fowler |
| author_sort | Panagiotis Filis |
| collection | DOAJ |
| description | 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 second trimester. Methods Thyroid glands and plasma were collected from fetuses electively terminated in the second 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. |
| first_indexed | 2024-12-21T16:49:15Z |
| format | Article |
| id | doaj.art-73fb813bced049b38e18195f406f755f |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-12-21T16:49:15Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-73fb813bced049b38e18195f406f755f2022-12-21T18:56:54ZengBMCBMC Medicine1741-70152018-10-0116111510.1186/s12916-018-1183-7Maternal smoking and high BMI disrupt thyroid gland developmentPanagiotis Filis0Sabine Hombach-Klonisch1Pierre Ayotte2Nalin Nagrath3Ugo Soffientini4Thomas Klonisch5Peter O’Shaughnessy6Paul A. Fowler7Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of AberdeenDepartment of Human Anatomy and Cell Science, Rady College of Medicine, Faculty of Health Sciences, University of ManitobaCentre de toxicologie, Institut National de Santé Publique du QuébecInstitute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of AberdeenInstitute of Biodiversity, Animal Health & Comparative Medicine (IBAHCM), College of Medical, Veterinary & Life Sciences, University of GlasgowDepartment of Human Anatomy and Cell Science, Rady College of Medicine, Faculty of Health Sciences, University of ManitobaInstitute of Biodiversity, Animal Health & Comparative Medicine (IBAHCM), College of Medical, Veterinary & Life Sciences, University of GlasgowInstitute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of AberdeenAbstract 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 second trimester. Methods Thyroid glands and plasma were collected from fetuses electively terminated in the second 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.http://link.springer.com/article/10.1186/s12916-018-1183-7FetusHumanThyroidMaternal smokingMaternal obesityThyroid hormones |
| spellingShingle | Panagiotis Filis Sabine Hombach-Klonisch Pierre Ayotte Nalin Nagrath Ugo Soffientini Thomas Klonisch Peter O’Shaughnessy Paul A. Fowler Maternal smoking and high BMI disrupt thyroid gland development BMC Medicine Fetus Human Thyroid Maternal smoking Maternal obesity Thyroid hormones |
| title | Maternal smoking and high BMI disrupt thyroid gland development |
| title_full | Maternal smoking and high BMI disrupt thyroid gland development |
| title_fullStr | Maternal smoking and high BMI disrupt thyroid gland development |
| title_full_unstemmed | Maternal smoking and high BMI disrupt thyroid gland development |
| title_short | Maternal smoking and high BMI disrupt thyroid gland development |
| title_sort | maternal smoking and high bmi disrupt thyroid gland development |
| topic | Fetus Human Thyroid Maternal smoking Maternal obesity Thyroid hormones |
| url | http://link.springer.com/article/10.1186/s12916-018-1183-7 |
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