Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous Abortion

Lin Qi,1,2,* Yong Yang,1,* Xiaofang Xie,1 Liping Xiang,3 Shuyun Zhang,3 Xue Li,3 Ling Zhou,3 Dan Zhao,1 Ningzheng Dong,2,4,5 Haifang Zhang,1 Hong Zhang3 1Department of Clinical Laboratory, the second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republi...

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Main Authors: Qi L, Yang Y, Xie X, Xiang L, Zhang S, Li X, Zhou L, Zhao D, Dong N, Zhang H
Format: Article
Language:English
Published: Dove Medical Press 2025-02-01
Series:International Journal of Women's Health
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Online Access:https://www.dovepress.com/elevated-homocysteine-levels-and-endothelial-dysfunction-in-unexplaine-peer-reviewed-fulltext-article-IJWH
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author Qi L
Yang Y
Xie X
Xiang L
Zhang S
Li X
Zhou L
Zhao D
Dong N
Zhang H
Zhang H
author_facet Qi L
Yang Y
Xie X
Xiang L
Zhang S
Li X
Zhou L
Zhao D
Dong N
Zhang H
Zhang H
author_sort Qi L
collection DOAJ
description Lin Qi,1,2,* Yong Yang,1,* Xiaofang Xie,1 Liping Xiang,3 Shuyun Zhang,3 Xue Li,3 Ling Zhou,3 Dan Zhao,1 Ningzheng Dong,2,4,5 Haifang Zhang,1 Hong Zhang3 1Department of Clinical Laboratory, the second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 2State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Gynaecology and Obstetrics,The second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 4Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Suzhou, Jiangsu, 215000, People’s Republic of China; 5MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, Medical College, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haifang Zhang, Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Gusu District, Suzhou, Jiangsu, 215000, People’s Republic of China, Tel +86 18896808917, Email haifangzhang@suda.edu.cn Hong Zhang, Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Gusu District, Suzhou, Jiangsu, 215000, People’s Republic of China, Tel +86 13814882907, Email Szzhanghong126@126.comBackground: Recurrent spontaneous abortion, a common condition in reproductive medicine, often arises from complex factors and lacks specific treatments. While studies have associated folate metabolism abnormalities with poor embryonic development, research on methionine metabolism, particularly homocysteine levels, has been limited.Methods: In this study, we analyzed blood samples from women with RSA and those with normal pregnancies.Results: We observed elevated homocysteine levels in women with RSA, which were correlated with increased total plasma microparticles, endothelial microparticles (EMPs), and free plasma DNA. Furthermore, we exposed human umbilical vein endothelial cells (HUVECs) to varying concentrations of homocysteine (0, 0.5, 1, 2, 4, 8 mmol/L). We found that higher homocysteine levels exacerbated its cytotoxic effects on HUVECs. Flow cytometry revealed that homocysteine compromised cell membrane integrity, enhanced membrane permeability, and promoted EMPs release. Our findings suggest that elevated homocysteine levels in women with RSA may induce significant endothelial cell apoptosis, leading to endothelial dysfunction and an increase in released microparticles and free DNA, potentially contributing to miscarriages.Conclusion: This study may contribute to understanding and exploring the underlying mechanisms of unexplained recurrent spontaneous abortion (URSA).Keywords: unexplained recurrent spontaneous abortion, homocysteine, microparticles, vascular endothelial cells, endothelium-derived microparticles, plasma DNA
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spelling doaj-art-c2a7fc2745084af09d3a46c78bf0d98e2025-08-20T02:13:23ZengDove Medical PressInternational Journal of Women's Health1179-14112025-02-01Volume 17429437100262Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous AbortionQi LYang YXie XXiang LZhang SLi XZhou LZhao DDong NZhang HZhang HLin Qi,1,2,* Yong Yang,1,* Xiaofang Xie,1 Liping Xiang,3 Shuyun Zhang,3 Xue Li,3 Ling Zhou,3 Dan Zhao,1 Ningzheng Dong,2,4,5 Haifang Zhang,1 Hong Zhang3 1Department of Clinical Laboratory, the second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 2State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Gynaecology and Obstetrics,The second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 4Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Suzhou, Jiangsu, 215000, People’s Republic of China; 5MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, Medical College, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haifang Zhang, Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Gusu District, Suzhou, Jiangsu, 215000, People’s Republic of China, Tel +86 18896808917, Email haifangzhang@suda.edu.cn Hong Zhang, Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Gusu District, Suzhou, Jiangsu, 215000, People’s Republic of China, Tel +86 13814882907, Email Szzhanghong126@126.comBackground: Recurrent spontaneous abortion, a common condition in reproductive medicine, often arises from complex factors and lacks specific treatments. While studies have associated folate metabolism abnormalities with poor embryonic development, research on methionine metabolism, particularly homocysteine levels, has been limited.Methods: In this study, we analyzed blood samples from women with RSA and those with normal pregnancies.Results: We observed elevated homocysteine levels in women with RSA, which were correlated with increased total plasma microparticles, endothelial microparticles (EMPs), and free plasma DNA. Furthermore, we exposed human umbilical vein endothelial cells (HUVECs) to varying concentrations of homocysteine (0, 0.5, 1, 2, 4, 8 mmol/L). We found that higher homocysteine levels exacerbated its cytotoxic effects on HUVECs. Flow cytometry revealed that homocysteine compromised cell membrane integrity, enhanced membrane permeability, and promoted EMPs release. Our findings suggest that elevated homocysteine levels in women with RSA may induce significant endothelial cell apoptosis, leading to endothelial dysfunction and an increase in released microparticles and free DNA, potentially contributing to miscarriages.Conclusion: This study may contribute to understanding and exploring the underlying mechanisms of unexplained recurrent spontaneous abortion (URSA).Keywords: unexplained recurrent spontaneous abortion, homocysteine, microparticles, vascular endothelial cells, endothelium-derived microparticles, plasma DNAhttps://www.dovepress.com/elevated-homocysteine-levels-and-endothelial-dysfunction-in-unexplaine-peer-reviewed-fulltext-article-IJWHunexplained recurrent spontaneous abortionhomocysteinemicroparticlesvascular endothelial cellsendothelium-derived microparticlesplasma dna
spellingShingle Qi L
Yang Y
Xie X
Xiang L
Zhang S
Li X
Zhou L
Zhao D
Dong N
Zhang H
Zhang H
Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous Abortion
International Journal of Women's Health
unexplained recurrent spontaneous abortion
homocysteine
microparticles
vascular endothelial cells
endothelium-derived microparticles
plasma dna
title Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous Abortion
title_full Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous Abortion
title_fullStr Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous Abortion
title_full_unstemmed Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous Abortion
title_short Elevated Homocysteine Levels and Endothelial Dysfunction in Unexplained Recurrent Spontaneous Abortion
title_sort elevated homocysteine levels and endothelial dysfunction in unexplained recurrent spontaneous abortion
topic unexplained recurrent spontaneous abortion
homocysteine
microparticles
vascular endothelial cells
endothelium-derived microparticles
plasma dna
url https://www.dovepress.com/elevated-homocysteine-levels-and-endothelial-dysfunction-in-unexplaine-peer-reviewed-fulltext-article-IJWH
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