Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial

Background: Severe endometrial injury constitutes a significant risk to female fertility, often leading to the development of intrauterine adhesions. Pyroptosis, a form of programmed cell death associated with inflammation, is initiated by the cleavage of gasdermin family proteins...

Full description

Saved in:
Bibliographic Details
Main Authors: Haiyan Shan, Mingyuan Xu, Jie Ni, Ling Zhou, Mengchun Xue, Jun Xue, Xiaohuan Yuan, Luyang Tao, Mingyang Zhang, Hong Zhang
Format: Article
Language:English
Published: IMR Press 2025-01-01
Series:Clinical and Experimental Obstetrics & Gynecology
Subjects:
Online Access:https://www.imrpress.com/journal/CEOG/52/1/10.31083/CEOG26554
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832586594586984448
author Haiyan Shan
Mingyuan Xu
Jie Ni
Ling Zhou
Mengchun Xue
Jun Xue
Xiaohuan Yuan
Luyang Tao
Mingyang Zhang
Hong Zhang
author_facet Haiyan Shan
Mingyuan Xu
Jie Ni
Ling Zhou
Mengchun Xue
Jun Xue
Xiaohuan Yuan
Luyang Tao
Mingyang Zhang
Hong Zhang
author_sort Haiyan Shan
collection DOAJ
description Background: Severe endometrial injury constitutes a significant risk to female fertility, often leading to the development of intrauterine adhesions. Pyroptosis, a form of programmed cell death associated with inflammation, is initiated by the cleavage of gasdermin family proteins by caspase, which has been implicated in endometrial injury. In recent years, hydrogen sulfide (H2S), a gaseous signaling molecule, exerts significant regulatory effects on pyroptosis in diverse pathological processes. The aim of this study is to elucidate the role of H2S in facilitating functional recovery of the endometrium following injury in a murine model. Methods: A prospective laboratory based randomized control trial was performed to evaluate the protective role of H2S in endometrial injury. Ethanol-induced endometrial injury mouse models were established and H2S donor sodium hydrosulfide (NaHS) was randomly administered to the injured mice. Western blot analysis was conducted to assess changes in the expression of endogenous H2S metabolism and pyroptosis-related markers and histological analysis (Hematoxylin & Eosin and Masson staining) was employed to examine alterations in endometrial morphology. Finally, a fertility test was performed to evaluate the restoration of the uterine function. Results: Following endometrial injury, the expression of key endogenous H2S enzymes-cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST)-is significantly reduced, while the levels of pyroptosis-related proteins are elevated (p < 0.05). However, treatment with H2S resulted in an increase in the expression of endogenous H2S enzymes and a decrease in pyroptosis-associated proteins compared to the Model group (p < 0.05). Moreover, endometrial morphology and embryo count showed the most pronounced improvement in the H2S treatment group (p < 0.05). Conclusions: This study confirms the therapeutic efficacy of H2S in facilitating the recovery of injured endometrium and revealed its potential therapeutic mechanism, offering a promising therapeutic avenue for patients with severe endometrial injury.
format Article
id doaj-art-ad791a2121b64528a263cfdb3ac61c29
institution Kabale University
issn 0390-6663
language English
publishDate 2025-01-01
publisher IMR Press
record_format Article
series Clinical and Experimental Obstetrics & Gynecology
spelling doaj-art-ad791a2121b64528a263cfdb3ac61c292025-01-25T07:14:26ZengIMR PressClinical and Experimental Obstetrics & Gynecology0390-66632025-01-015212655410.31083/CEOG26554S0390-6663(24)02544-2Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control TrialHaiyan Shan0Mingyuan Xu1Jie Ni2Ling Zhou3Mengchun Xue4Jun Xue5Xiaohuan Yuan6Luyang Tao7Mingyang Zhang8Hong Zhang9Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 215123 Suzhou, Jiangsu, ChinaDepartment of Forensic Medicine, School of Basic Medicine, Suzhou Medical College of Soochow University, 215123 Suzhou, Jiangsu, ChinaDepartment of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 215123 Suzhou, Jiangsu, ChinaDepartment of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 215123 Suzhou, Jiangsu, ChinaCollege of Life Sciences, Mudanjiang Medical University, 157011 Mudanjiang, Heilongjiang, ChinaCollege of Life Sciences, Mudanjiang Medical University, 157011 Mudanjiang, Heilongjiang, ChinaCollege of Life Sciences, Mudanjiang Medical University, 157011 Mudanjiang, Heilongjiang, ChinaDepartment of Forensic Medicine, School of Basic Medicine, Suzhou Medical College of Soochow University, 215123 Suzhou, Jiangsu, ChinaDepartment of Forensic Medicine, School of Basic Medicine, Suzhou Medical College of Soochow University, 215123 Suzhou, Jiangsu, ChinaDepartment of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 215123 Suzhou, Jiangsu, ChinaBackground: Severe endometrial injury constitutes a significant risk to female fertility, often leading to the development of intrauterine adhesions. Pyroptosis, a form of programmed cell death associated with inflammation, is initiated by the cleavage of gasdermin family proteins by caspase, which has been implicated in endometrial injury. In recent years, hydrogen sulfide (H2S), a gaseous signaling molecule, exerts significant regulatory effects on pyroptosis in diverse pathological processes. The aim of this study is to elucidate the role of H2S in facilitating functional recovery of the endometrium following injury in a murine model. Methods: A prospective laboratory based randomized control trial was performed to evaluate the protective role of H2S in endometrial injury. Ethanol-induced endometrial injury mouse models were established and H2S donor sodium hydrosulfide (NaHS) was randomly administered to the injured mice. Western blot analysis was conducted to assess changes in the expression of endogenous H2S metabolism and pyroptosis-related markers and histological analysis (Hematoxylin & Eosin and Masson staining) was employed to examine alterations in endometrial morphology. Finally, a fertility test was performed to evaluate the restoration of the uterine function. Results: Following endometrial injury, the expression of key endogenous H2S enzymes-cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST)-is significantly reduced, while the levels of pyroptosis-related proteins are elevated (p < 0.05). However, treatment with H2S resulted in an increase in the expression of endogenous H2S enzymes and a decrease in pyroptosis-associated proteins compared to the Model group (p < 0.05). Moreover, endometrial morphology and embryo count showed the most pronounced improvement in the H2S treatment group (p < 0.05). Conclusions: This study confirms the therapeutic efficacy of H2S in facilitating the recovery of injured endometrium and revealed its potential therapeutic mechanism, offering a promising therapeutic avenue for patients with severe endometrial injury.https://www.imrpress.com/journal/CEOG/52/1/10.31083/CEOG26554endometrial injuryhydrogen sulfideintrauterine adhesionspyroptosis
spellingShingle Haiyan Shan
Mingyuan Xu
Jie Ni
Ling Zhou
Mengchun Xue
Jun Xue
Xiaohuan Yuan
Luyang Tao
Mingyang Zhang
Hong Zhang
Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial
Clinical and Experimental Obstetrics & Gynecology
endometrial injury
hydrogen sulfide
intrauterine adhesions
pyroptosis
title Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial
title_full Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial
title_fullStr Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial
title_full_unstemmed Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial
title_short Hydrogen Sulfide Promotes Functional Endometrium Recovery via Regulating Pyroptosis in Severe Endometrial Injury: A Prospective Laboratory Based Randomized Control Trial
title_sort hydrogen sulfide promotes functional endometrium recovery via regulating pyroptosis in severe endometrial injury a prospective laboratory based randomized control trial
topic endometrial injury
hydrogen sulfide
intrauterine adhesions
pyroptosis
url https://www.imrpress.com/journal/CEOG/52/1/10.31083/CEOG26554
work_keys_str_mv AT haiyanshan hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT mingyuanxu hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT jieni hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT lingzhou hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT mengchunxue hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT junxue hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT xiaohuanyuan hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT luyangtao hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT mingyangzhang hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial
AT hongzhang hydrogensulfidepromotesfunctionalendometriumrecoveryviaregulatingpyroptosisinsevereendometrialinjuryaprospectivelaboratorybasedrandomizedcontroltrial