Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulation

Objectives Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder affecting pregnancy, leading to significant maternal and fetal complications. This study investigates the expression of M3 muscarinic acetylcholine receptor (mAChR) in GDM placentas and its potential implications for pl...

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Main Authors: Süleyman Cemil Oğlak, Fırat Aşır, Tuğcan Korak, Ayşegül Aşır, Emine Zeynep Yılmaz, Elif Ağaçayak
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:The Journal of Maternal-Fetal & Neonatal Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/14767058.2025.2521799
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author Süleyman Cemil Oğlak
Fırat Aşır
Tuğcan Korak
Ayşegül Aşır
Emine Zeynep Yılmaz
Elif Ağaçayak
author_facet Süleyman Cemil Oğlak
Fırat Aşır
Tuğcan Korak
Ayşegül Aşır
Emine Zeynep Yılmaz
Elif Ağaçayak
author_sort Süleyman Cemil Oğlak
collection DOAJ
description Objectives Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder affecting pregnancy, leading to significant maternal and fetal complications. This study investigates the expression of M3 muscarinic acetylcholine receptor (mAChR) in GDM placentas and its potential implications for placental function.Methods A case–control study was conducted on placental samples from 40 GDM and 40 healthy pregnancies. Immunohistochemical (IHC) analysis was performed to evaluate M3 mAChR expression, and semi-quantitative assessments were conducted using ImageJ software. Placental samples of patients were tested with an ELISA kit. In-silico functional annotation analysis, including protein-protein interaction and KEGG pathway analysis, was utilized to explore the biological pathways associated with M3 mAChR dysregulation in GDM.Results Histopathological examination revealed significant structural alterations in GDM placentas, including increased fibrin deposition, syncytial knots, vascular congestion, and cellular degeneration. IHC analysis and tissue homogenate ELISA measurement demonstrated a significant reduction in M3 mAChR expression in GDM placentas compared to controls (p < 0.0001). KEGG pathway analysis of shared M3 mAChR and GDM protein targets revealed significant enrichment in endocrine, metabolic, vascular, cardiac, and neuroactive signaling pathways, suggesting their involvement in M3 mAChR-associated GDM mechanisms (false discovery rate [FDR] < 0.05).Conclusion The findings suggest that reduced M3 mAChR expression in GDM placentas may contribute to impaired cholinergic signaling, vascular dysfunction, and placental insufficiency. These alterations may play a role in the adverse pregnancy outcomes associated with GDM.
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publishDate 2025-12-01
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spelling doaj-art-5a7a6bc8f57f490a9338f09ea2b7cd112025-08-20T03:47:19ZengTaylor & Francis GroupThe Journal of Maternal-Fetal & Neonatal Medicine1476-70581476-49542025-12-0138110.1080/14767058.2025.2521799Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulationSüleyman Cemil Oğlak0Fırat Aşır1Tuğcan Korak2Ayşegül Aşır3Emine Zeynep Yılmaz4Elif Ağaçayak5Department of Obstetrics and Gynecology, Health Sciences University, Gazi Yaşargil Training and Research Hospital, Diyarbakır, TurkeyDepartment of Histology and Embryology, Dicle University Faculty of Medicine, Diyarbakır, TurkeyDepartment of Medical Biology, Kocaeli University Faculty of Medicine, Kocaeli, TurkeyDepartment of Pediatrics, Health Sciences University, Gazi Yaşargil Training and Research Hospital, Diyarbakır, TurkeyDepartment of Obstetrics and Gynecology, Bahçelievler Memorial Hospital, Istanbul, TurkeyDepartment of Obstetrics and Gynecology, Dicle University Faculty of Medicine, Diyarbakır, TurkeyObjectives Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder affecting pregnancy, leading to significant maternal and fetal complications. This study investigates the expression of M3 muscarinic acetylcholine receptor (mAChR) in GDM placentas and its potential implications for placental function.Methods A case–control study was conducted on placental samples from 40 GDM and 40 healthy pregnancies. Immunohistochemical (IHC) analysis was performed to evaluate M3 mAChR expression, and semi-quantitative assessments were conducted using ImageJ software. Placental samples of patients were tested with an ELISA kit. In-silico functional annotation analysis, including protein-protein interaction and KEGG pathway analysis, was utilized to explore the biological pathways associated with M3 mAChR dysregulation in GDM.Results Histopathological examination revealed significant structural alterations in GDM placentas, including increased fibrin deposition, syncytial knots, vascular congestion, and cellular degeneration. IHC analysis and tissue homogenate ELISA measurement demonstrated a significant reduction in M3 mAChR expression in GDM placentas compared to controls (p < 0.0001). KEGG pathway analysis of shared M3 mAChR and GDM protein targets revealed significant enrichment in endocrine, metabolic, vascular, cardiac, and neuroactive signaling pathways, suggesting their involvement in M3 mAChR-associated GDM mechanisms (false discovery rate [FDR] < 0.05).Conclusion The findings suggest that reduced M3 mAChR expression in GDM placentas may contribute to impaired cholinergic signaling, vascular dysfunction, and placental insufficiency. These alterations may play a role in the adverse pregnancy outcomes associated with GDM.https://www.tandfonline.com/doi/10.1080/14767058.2025.2521799Gestational diabetes mellitusM3 muscarinic acetylcholine receptorimmunohistochemistrycholinergic signalingvascular regulation
spellingShingle Süleyman Cemil Oğlak
Fırat Aşır
Tuğcan Korak
Ayşegül Aşır
Emine Zeynep Yılmaz
Elif Ağaçayak
Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulation
The Journal of Maternal-Fetal & Neonatal Medicine
Gestational diabetes mellitus
M3 muscarinic acetylcholine receptor
immunohistochemistry
cholinergic signaling
vascular regulation
title Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulation
title_full Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulation
title_fullStr Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulation
title_full_unstemmed Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulation
title_short Reduced M3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus: implications for placental dysfunction and vascular regulation
title_sort reduced m3 muscarinic acetylcholine receptor expression in gestational diabetes mellitus implications for placental dysfunction and vascular regulation
topic Gestational diabetes mellitus
M3 muscarinic acetylcholine receptor
immunohistochemistry
cholinergic signaling
vascular regulation
url https://www.tandfonline.com/doi/10.1080/14767058.2025.2521799
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