Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage

Abstract Background It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. Me...

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Main Authors: Zhen Yu, Xinghao Feng, Zhongshan Lin, Xuan Li, Shiyue Su, Huiru Cheng, Yuanyuan Yang, Zhaolian Wei
Format: Article
Language:English
Published: BMC 2023-11-01
Series:Reproductive Biology and Endocrinology
Subjects:
Online Access:https://doi.org/10.1186/s12958-023-01142-1
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author Zhen Yu
Xinghao Feng
Zhongshan Lin
Xuan Li
Shiyue Su
Huiru Cheng
Yuanyuan Yang
Zhaolian Wei
author_facet Zhen Yu
Xinghao Feng
Zhongshan Lin
Xuan Li
Shiyue Su
Huiru Cheng
Yuanyuan Yang
Zhaolian Wei
author_sort Zhen Yu
collection DOAJ
description Abstract Background It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. Methods Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. Results Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRβ, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRβ. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. Conclusion Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.
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spelling doaj.art-93e71315bed64cafaabd18afe06dc3972023-11-20T11:19:06ZengBMCReproductive Biology and Endocrinology1477-78272023-11-0121111210.1186/s12958-023-01142-1Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriageZhen Yu0Xinghao Feng1Zhongshan Lin2Xuan Li3Shiyue Su4Huiru Cheng5Yuanyuan Yang6Zhaolian Wei7Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityAbstract Background It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. Methods Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. Results Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRβ, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRβ. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. Conclusion Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.https://doi.org/10.1186/s12958-023-01142-1MiscarriageAngiogenesisThyroid hormoneTransthyretinDeiodinase
spellingShingle Zhen Yu
Xinghao Feng
Zhongshan Lin
Xuan Li
Shiyue Su
Huiru Cheng
Yuanyuan Yang
Zhaolian Wei
Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage
Reproductive Biology and Endocrinology
Miscarriage
Angiogenesis
Thyroid hormone
Transthyretin
Deiodinase
title Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage
title_full Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage
title_fullStr Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage
title_full_unstemmed Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage
title_short Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage
title_sort thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage
topic Miscarriage
Angiogenesis
Thyroid hormone
Transthyretin
Deiodinase
url https://doi.org/10.1186/s12958-023-01142-1
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