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Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta
BACKGROUND: Maternal high blood glucose during pregnancy increases the risk for both maternal and fetal adverse outcomes. The mechanisms underlying the regulator effects of hyperglycemia on placental development and growth have not been fully illustrated yet. The placenta expresses high amounts of b...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988311/ https://www.ncbi.nlm.nih.gov/pubmed/33776919 http://dx.doi.org/10.3389/fendo.2021.621680 |
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author | Tumminia, Andrea Scalisi, Nunzio M. Milluzzo, Agostino Ettore, Giuseppe Vigneri, Riccardo Sciacca, Laura |
author_facet | Tumminia, Andrea Scalisi, Nunzio M. Milluzzo, Agostino Ettore, Giuseppe Vigneri, Riccardo Sciacca, Laura |
author_sort | Tumminia, Andrea |
collection | PubMed |
description | BACKGROUND: Maternal high blood glucose during pregnancy increases the risk for both maternal and fetal adverse outcomes. The mechanisms underlying the regulator effects of hyperglycemia on placental development and growth have not been fully illustrated yet. The placenta expresses high amounts of both insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R). It has been reported that the placenta of diabetic women has structural and functional alterations and the insulin/IGF system is likely to play a role in these changes. The aim of the present study was to measure the content of IR and IGF-1R and their phosphorylation in the placenta of women with type 1 diabetes mellitus (T1D) or with gestational diabetes mellitus (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy. METHODS: Placental tissues were obtained from 80 Caucasian women with a singleton pregnancy. In particular, we collected placenta samples from 20 T1D patients, 20 GDM patients and 40 NGT women during pregnancy. Clinical characteristics and anthropometric measures of all women as well as delivery and newborn characteristics were recorded. Patients were also subdivided on the basis of peripartum glycemia either ≥90 mg/dl or <90 mg/dl, regardless of the diagnosis. RESULTS: In T1D patients, a higher rate of adverse outcomes was observed. Compared to the GDM women, the T1D group showed significantly higher average capillary blood glucose levels at the third trimester of pregnancy and at peripartum, and higher third-trimester HbA1c values. In both T1D and GDM women, HbA1c values during pregnancy correlated with glucose values in the peripartum period (R-squared 0.14, p=0.02). A positive correlation was observed between phosphorylation of placental IR and the glucose levels during the third trimester of GDM and T1D pregnancy (R-squared 0.21, p=0.003). In the placenta of T1D patients, IGF-1R phosphorylation and IR isoform A (IR-A) expression were significantly increased (p=0.006 and p=0.040, respectively), compared to the NGT women. Moreover, IGF-1R phosphorylation was significantly increased (p<0.0001) in the placenta of patients with peripartum glucose >90 mg/dl, while IR-A expression was increased in those with peripartum blood glucose higher than 120 mg/dl (p=0.046). CONCLUSIONS: To the best of our knowledge, our study represents the first one in which an increased maternal blood glucose level during pregnancy is associated with an increased IGF-1R phosphorylation and IR-A expression in the placenta. Both these mechanisms can promote an excessive fetal growth. |
format | Online Article Text |
id | pubmed-7988311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79883112021-03-25 Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta Tumminia, Andrea Scalisi, Nunzio M. Milluzzo, Agostino Ettore, Giuseppe Vigneri, Riccardo Sciacca, Laura Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Maternal high blood glucose during pregnancy increases the risk for both maternal and fetal adverse outcomes. The mechanisms underlying the regulator effects of hyperglycemia on placental development and growth have not been fully illustrated yet. The placenta expresses high amounts of both insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R). It has been reported that the placenta of diabetic women has structural and functional alterations and the insulin/IGF system is likely to play a role in these changes. The aim of the present study was to measure the content of IR and IGF-1R and their phosphorylation in the placenta of women with type 1 diabetes mellitus (T1D) or with gestational diabetes mellitus (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy. METHODS: Placental tissues were obtained from 80 Caucasian women with a singleton pregnancy. In particular, we collected placenta samples from 20 T1D patients, 20 GDM patients and 40 NGT women during pregnancy. Clinical characteristics and anthropometric measures of all women as well as delivery and newborn characteristics were recorded. Patients were also subdivided on the basis of peripartum glycemia either ≥90 mg/dl or <90 mg/dl, regardless of the diagnosis. RESULTS: In T1D patients, a higher rate of adverse outcomes was observed. Compared to the GDM women, the T1D group showed significantly higher average capillary blood glucose levels at the third trimester of pregnancy and at peripartum, and higher third-trimester HbA1c values. In both T1D and GDM women, HbA1c values during pregnancy correlated with glucose values in the peripartum period (R-squared 0.14, p=0.02). A positive correlation was observed between phosphorylation of placental IR and the glucose levels during the third trimester of GDM and T1D pregnancy (R-squared 0.21, p=0.003). In the placenta of T1D patients, IGF-1R phosphorylation and IR isoform A (IR-A) expression were significantly increased (p=0.006 and p=0.040, respectively), compared to the NGT women. Moreover, IGF-1R phosphorylation was significantly increased (p<0.0001) in the placenta of patients with peripartum glucose >90 mg/dl, while IR-A expression was increased in those with peripartum blood glucose higher than 120 mg/dl (p=0.046). CONCLUSIONS: To the best of our knowledge, our study represents the first one in which an increased maternal blood glucose level during pregnancy is associated with an increased IGF-1R phosphorylation and IR-A expression in the placenta. Both these mechanisms can promote an excessive fetal growth. Frontiers Media S.A. 2021-03-10 /pmc/articles/PMC7988311/ /pubmed/33776919 http://dx.doi.org/10.3389/fendo.2021.621680 Text en Copyright © 2021 Tumminia, Scalisi, Milluzzo, Ettore, Vigneri and Sciacca http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Tumminia, Andrea Scalisi, Nunzio M. Milluzzo, Agostino Ettore, Giuseppe Vigneri, Riccardo Sciacca, Laura Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta |
title | Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta |
title_full | Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta |
title_fullStr | Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta |
title_full_unstemmed | Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta |
title_short | Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta |
title_sort | maternal diabetes impairs insulin and igf-1 receptor expression and signaling in human placenta |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988311/ https://www.ncbi.nlm.nih.gov/pubmed/33776919 http://dx.doi.org/10.3389/fendo.2021.621680 |
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