Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway
Abstract Background It is unclear whether the offspring of subclinical hypothyroidism (SCH) pregnant rats still have abnormal cardiac development, and whether early intervention with L-T4 can improve the abnormality of these offspring. Therefore, the aim of this study was to investigate the effect o...
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | BMC Cardiovascular Disorders |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12872-020-01646-3 |
| _version_ | 1818442108247212032 |
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| author | D. Xue J. L. Sun J. Yang |
| author_facet | D. Xue J. L. Sun J. Yang |
| author_sort | D. Xue |
| collection | DOAJ |
| description | Abstract Background It is unclear whether the offspring of subclinical hypothyroidism (SCH) pregnant rats still have abnormal cardiac development, and whether early intervention with L-T4 can improve the abnormality of these offspring. Therefore, the aim of this study was to investigate the effect of early L-T4 intervention on the heart development of offspring of SCH pregnant rats and its possible molecular mechanism. Methods Eighty female Wistar rats were randomly divided into Sham group (placebo control), SCH group, LT4-E10 group (L-T4 treatment started on the 10th day of gestation), and LT4-E13 group (L-T4 treatment started on the 13th day of gestation). Each group was further divided into E16 (16th day of gestation), E18 (18th day of gestation), P5 (5th day postnatal day), and P10 (10th day postnatal day) subgroups. The levels of serum TT4 and TSH, the ratio of heart weight to body weight of offspring rats, the expression of metabolic enzymes, and the histopathology of cardiomyocytes were determined. To elucidate the effects of L-T4 on cardiac development of offspring of SCH pregnant rats, the expression levels of GATA4, Nkx2–5 and proteins involved in BMP4/Smad4 signaling pathway were detected by immunohistochemistry, real time quantitative polymerase chain reaction and Western blotting to elucidate the molecular mechanism of L-T4 regulating the heart development of the offspring of SCH pregnant rats. Results Compared with Sham group, serum TSH was significantly increased in SCH pregnant rats. Moreover, early L-T4 intervention significantly reduced the levels of serum TSH. Compared with the offspring in the SCH group, early L-T4 intervention significantly increased the heart weight, heart weight to body weight ratio, the activities of succinate dehydrogenase (SDH), Na+/K+-ATPase and Ca2+-ATPase, but reduced myocardial cell shrinkage and nuclear staining, hyperemia/congestion and vacuolar degeneration. In addition, early L-T4 intervention not only significantly increased the mRNA and protein expression of Gata4 and Nkx2–5, but also increased the protein expression involved in BMP4/Smad4 signal pathway in myocardium of the offspring of SCH pregnant rats. Conclusions Early L-T4 intervention can regulate the cardiac development of the offspring of SCH pregnant rats by activating BMP4/Smad4 signaling pathway and increasing the expression of Gata4 and Nkx2–5 proteins. |
| first_indexed | 2024-12-14T18:38:54Z |
| format | Article |
| id | doaj.art-caa5b96cc95141f7b53bb7cfa2de35d7 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-12-14T18:38:54Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-caa5b96cc95141f7b53bb7cfa2de35d72022-12-21T22:51:33ZengBMCBMC Cardiovascular Disorders1471-22612020-08-0120111010.1186/s12872-020-01646-3Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathwayD. Xue0J. L. Sun1J. Yang2Department of Cardiovascular Ultrasound, The First Hospital of China Medical UniversityDepartment of Gynaecology and Obstetrics, General Hospital of Northern Theater CommandDepartment of Cardiovascular Ultrasound, The First Hospital of China Medical UniversityAbstract Background It is unclear whether the offspring of subclinical hypothyroidism (SCH) pregnant rats still have abnormal cardiac development, and whether early intervention with L-T4 can improve the abnormality of these offspring. Therefore, the aim of this study was to investigate the effect of early L-T4 intervention on the heart development of offspring of SCH pregnant rats and its possible molecular mechanism. Methods Eighty female Wistar rats were randomly divided into Sham group (placebo control), SCH group, LT4-E10 group (L-T4 treatment started on the 10th day of gestation), and LT4-E13 group (L-T4 treatment started on the 13th day of gestation). Each group was further divided into E16 (16th day of gestation), E18 (18th day of gestation), P5 (5th day postnatal day), and P10 (10th day postnatal day) subgroups. The levels of serum TT4 and TSH, the ratio of heart weight to body weight of offspring rats, the expression of metabolic enzymes, and the histopathology of cardiomyocytes were determined. To elucidate the effects of L-T4 on cardiac development of offspring of SCH pregnant rats, the expression levels of GATA4, Nkx2–5 and proteins involved in BMP4/Smad4 signaling pathway were detected by immunohistochemistry, real time quantitative polymerase chain reaction and Western blotting to elucidate the molecular mechanism of L-T4 regulating the heart development of the offspring of SCH pregnant rats. Results Compared with Sham group, serum TSH was significantly increased in SCH pregnant rats. Moreover, early L-T4 intervention significantly reduced the levels of serum TSH. Compared with the offspring in the SCH group, early L-T4 intervention significantly increased the heart weight, heart weight to body weight ratio, the activities of succinate dehydrogenase (SDH), Na+/K+-ATPase and Ca2+-ATPase, but reduced myocardial cell shrinkage and nuclear staining, hyperemia/congestion and vacuolar degeneration. In addition, early L-T4 intervention not only significantly increased the mRNA and protein expression of Gata4 and Nkx2–5, but also increased the protein expression involved in BMP4/Smad4 signal pathway in myocardium of the offspring of SCH pregnant rats. Conclusions Early L-T4 intervention can regulate the cardiac development of the offspring of SCH pregnant rats by activating BMP4/Smad4 signaling pathway and increasing the expression of Gata4 and Nkx2–5 proteins.http://link.springer.com/article/10.1186/s12872-020-01646-3Subclinical hypothyroidismCardiac developmentPregnant ratsL-T4BMP4/Smad4 signaling pathway |
| spellingShingle | D. Xue J. L. Sun J. Yang Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway BMC Cardiovascular Disorders Subclinical hypothyroidism Cardiac development Pregnant rats L-T4 BMP4/Smad4 signaling pathway |
| title | Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway |
| title_full | Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway |
| title_fullStr | Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway |
| title_full_unstemmed | Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway |
| title_short | Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway |
| title_sort | early l t4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating bmp4 smad4 signaling pathway |
| topic | Subclinical hypothyroidism Cardiac development Pregnant rats L-T4 BMP4/Smad4 signaling pathway |
| url | http://link.springer.com/article/10.1186/s12872-020-01646-3 |
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