Reproductive SciencesPub Date : 2025-05-01Epub Date: 2024-07-02DOI: 10.1007/s43032-024-01630-8
Lin Liu, Yidan Liu, Yu Tian, Ying Cao, Ting Wang, Shengyan Mi, Run Yang, Simin Liu, Xiaoling Ma, Jing Wang
{"title":"Identification of Differentially Expressed mRNAs and lncRNAs Contributes to Elucidation of Underlying Pathogenesis and Therapeutic Strategy of Recurrent Implantation Failure.","authors":"Lin Liu, Yidan Liu, Yu Tian, Ying Cao, Ting Wang, Shengyan Mi, Run Yang, Simin Liu, Xiaoling Ma, Jing Wang","doi":"10.1007/s43032-024-01630-8","DOIUrl":"10.1007/s43032-024-01630-8","url":null,"abstract":"<p><p>Recurrent implantation failure (RIF) is a complex and poorly understood clinical disorder characterized by failure to conceive after repeated embryo transfers. Endometrial receptivity (ER) is a prerequisite for implantation, and ER disorders are associated with RIF. However, little is known regarding the molecular mechanisms underlying ER in RIF. In the present study, RNA sequencing data from the mid-secretory endometrium of patients with and without RIF were analyzed to explore the potential long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in RIF. The analysis revealed 213 and 1485 differentially expressed mRNAs and lncRNAs, respectively (fold change ≥ 2 and p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these genes were mostly involved in processes related to immunity or inflammation. 5 key genes (TTR, ALB, TF, AFP, and CFTR) and a key module including 14 hub genes (AFP, ALB, APOA1, APOA2, APOB, APOH, FABP1, FGA, FGG, GC, ITIH2, SERPIND1, TF and TTR) were identified in the protein-protein interaction (PPI) network. The 5 key genes were used to further explore the lncRNA-miRNA-mRNA regulatory network. Finally, the drug ML-193 based on the 14 hub genes was identifed through the CMap. After ML-193 treatment, endometrial cell proliferation was increased, the hub genes were mostly down-regulated, and the ER marker HOXA10 was up-regulated. These results offer insights into the regulatory mechanisms of lncRNAs and mRNAs and suggest ML-193 as a therapeutic agent for RIF by enhancing ER.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1477-1490"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-05-01Epub Date: 2024-10-08DOI: 10.1007/s43032-024-01722-5
Xiang Fan, Ni Yang, Gu Huang, Yishan Dong, Pengfeng Zhu
{"title":"Correlation study of NF-κB, IER3, and Recurrence of Ovarian Endometrioid Cysts.","authors":"Xiang Fan, Ni Yang, Gu Huang, Yishan Dong, Pengfeng Zhu","doi":"10.1007/s43032-024-01722-5","DOIUrl":"10.1007/s43032-024-01722-5","url":null,"abstract":"<p><p>The study aimed to investigate the expression of nuclear actor-k-gene binding(NF-κB) and immediate early response 3(IER3) in ovarian endometrioid cysts and its correlation with the recurrence of the ovarian endometrioid cyst. From January 2018 to March 2019, a total of 88 patients who underwent laparoscopic ovarian cyst excision due to ovarian endometrioid cyst in Changzhou Maternity and Child Health Care Hospital were selected. Clinical data of the patients were collected. The patient's Revised American Fertility Society (R-AFS) score, least function(LF) score, and endometriosis fertility index (EFI) were calculated. Immunohistochemistry was performed to detect the expression of IER3 and NF-κB. The receiver-operating characteristic (ROC) curve was used to evaluate the predictive value of IER3 and NF-κB expression on postoperative recurrence. Cox regression was fitted to analyze the influencing factors of ovarian endometrioid cyst recurrence. The expression of NF-κB was positively correlated with IER3 (P < 0.001). ROC curve showed that NF-κB combined with IER3 had higher predictive value for disease recurrence. Multivariate Cox regression showed that the IER3 expression intensity > 4.5 (HR = 3.418,95%CI: 1.227 ~ 9.523, P = 0.019) and the NF-κB expression intensity > 4.5 (HR = 5.491,95%CI: 1.600 ~ 18.838, P = 0.007) were independent risk factors for recurrence, and EFI score (HR = 0.791,95%CI: 0.637 ~ 0.983, P = 0.035) was a protective factor for recurrence. Our results suggested that EFI score is a protective factor for recurrence. The expression levels of NF-κB and IER3 > 4.5 are correlated with the recurrence of ovarian endometrioid cysts and independent risk factors for recurrence.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1520-1529"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-05-01Epub Date: 2025-03-17DOI: 10.1007/s43032-025-01841-7
Li Yan, Yang Wang, Huiyu Zhang, Bangchun Lu, Jinglan Liu, Yamei Li, Juan Li, Jian Zhang
{"title":"Deeper Trophoblastic Invasion and More-Promotive Vascular Remodeling in Tubal Isthmic Pregnancy Compared with Ampullary Pregnancy: A Retrospective Clinicopathological Study.","authors":"Li Yan, Yang Wang, Huiyu Zhang, Bangchun Lu, Jinglan Liu, Yamei Li, Juan Li, Jian Zhang","doi":"10.1007/s43032-025-01841-7","DOIUrl":"10.1007/s43032-025-01841-7","url":null,"abstract":"<p><p>To explore clinical and pathological characteristics of tubal isthmic pregnancy. A single-center, retrospective clinicopathological cohort study was conducted in women diagnosed with tubal pregnancy that underwent salpingectomy in International Peace Maternal and Child Health Care Hospital from January 2018 to April 2023. A total of 598 eligible women with tubal pregnancy were included in the analysis, including 75 women with isthmic pregnancy and 523 women with ampullary pregnancy. Among women with isthmic pregnancy, 29 (38.67%) had trophoblastic infiltration into the muscular layer, while 46 (61.33%) had infiltration into the serosal layer. Meanwhile 66 (12.62%) women, 258 (49.33%) women, and 199 (38.05%) women had trophoblastic infiltration into the mucosal layer, muscular layer, and serosal layer of the ampullary pregnancy, respectively. The study found that women with isthmic pregnancy had enhanced trophoblastic activity, deeper vascular remodeling, increased trophoblastic infiltration into the deep wall of the tube, higher serum beta subunit of human chorionic gonadotropin (β-hCG) levels, and a higher probability of clinical manifestations. Additionally compared with ampullary pregnancy, the occurrence of isthmic pregnancy was positively correlated with salpingitis isthmica nodosa (AOR = 3.62, 95% CI 1.45-9.00, P < 0.01), and negatively correlated with the presence of chronic tubal inflammation (AOR = 0.24, 95% CI 0.09-0.64, P < 0.01). Salpingitis isthmica nodosa, not chronic inflammation of the fallopian tubes, may be a risk factor for isthmic pregnancy. Compared to ampullary pregnancy, isthmic pregnancy exhibits a more profound trophoblastic vascular remodeling of the fallopian tube and a greater tendency to infiltrate the deep layers of the tubal wall. These characteristics render it more concealed and perilous, underscoring the importance of early recognition and diagnosis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1743-1755"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-05-01Epub Date: 2025-01-16DOI: 10.1007/s43032-024-01777-4
Shu-Han Yang, Jie Gan, Hao-Ran Xu, Jia-Xin Shi, Jian Wang, Xuan Zhang
{"title":"The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.","authors":"Shu-Han Yang, Jie Gan, Hao-Ran Xu, Jia-Xin Shi, Jian Wang, Xuan Zhang","doi":"10.1007/s43032-024-01777-4","DOIUrl":"10.1007/s43032-024-01777-4","url":null,"abstract":"<p><p>The maintenance of early pregnancy is a complex and distinctive process, primarily characterized by critical reproductive events such as embryo implantation, trophoblasts differentiation, decidualization, and extravillous trophoblasts (EVTs) invasion etc. However, dysregulation of these essential reproductive processes can result in various pregnancy complications, including recurrent miscarriage, preeclampsia, and fetal growth restriction etc. Notably, these complications exhibit an interconnected regulatory network that suggests shared underlying pathophysiological mechanisms. Meanwhile, the role of the BMP signaling pathway in sustaining early pregnancy is increasingly being investigated and elucidated. In this review, we have clarified the specific molecular mechanisms which are fundamental to essential reproductive processes and summarize an overview of animal models associated with BMP signaling molecules. In addition, we present a novel perspective on several contentious viewpoints regarding the functional roles of BMP ligands. Therefore, we anticipated a comprehensive understanding of the precise ways in which the BMP signaling pathway affects reproductive events during early pregnancy could provide new perspectives and approaches for preventing and addressing early pregnancy complications.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1427-1445"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cancer-associated Fibroblasts-derived Exosomes with HOXD11 Overexpression Promote Ovarian Cancer Cell Angiogenesis Via FN1.","authors":"Chunfei Chen, Fahui Wang, Chunling Cheng, Hongxin Li, Yadan Fan, Liping Jia","doi":"10.1007/s43032-024-01716-3","DOIUrl":"10.1007/s43032-024-01716-3","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) represent a critical stromal component of metastatic niche and promote metastasis in patients with ovarian cancer (OC). Here, we try to further understand the mechanism by which CAFs-derived exosomes (CAFs-Exo) promoted angiogenesis in OC. We intersected differentially expressed genes in OC cells after CAFs-Exo treatment in the GSE147610 dataset with a list of transcription factors to identify homeobox protein hox-D11 (HOXD11) as a possible cargo of CAFs-Exo. HOXD11 encapsulated by CAFs-Exo enhanced colony formation, migration, and invasion of OC cells. HOXD11 bound to the promoter of fibronectin (FN1) and promoted its transcription. HOXD11 knockdown from CAFs-Exo significantly repressed the VEGF and CD31 protein expression and tube formation, viability, and migration of human umbilical vein endothelial cells (HUVEC) and slowed angiogenesis and tumor growth in mice. Furthermore, we found that overexpression of FN1 increased the expression of angiogenic factors and activity of HUVEC in the presence of HOXD11 knockdown. These results verify the significant contribution of CAFs-Exo to angiogenesis in OC, which could be partially due to the promotion of FN1 mediated by HOXD11.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1530-1544"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-05-01Epub Date: 2025-02-27DOI: 10.1007/s43032-025-01836-4
Ye Shen, Hua Fang, Wenmiao Si, Min Zhao, Fangbo Qian, Qi Chen
{"title":"An Analysis of Contraceptive Use in Women with a Previous Live Birth in a Single Tertiary Women's Hospital: A Survey Study.","authors":"Ye Shen, Hua Fang, Wenmiao Si, Min Zhao, Fangbo Qian, Qi Chen","doi":"10.1007/s43032-025-01836-4","DOIUrl":"10.1007/s43032-025-01836-4","url":null,"abstract":"<p><p>The use of contraceptives to prevent unintended pregnancies is not widely accepted in developing countries due to social and cultural factors, lack of knowledge, and limited access to contraceptive services. This results in a relatively high incidence of repeat abortions in women with live births. The objective of this study is to understand the awareness of contraceptive use in women with live births women with previous live births who currently underwent an abortion (n = 272) and women who had a recent live birth (n = 323) voluntarily participated in this survey. Among women with previous live births, 22% did not use contraceptives in the past, and 41% well understood the importance of contraceptive use. There were no differences in educational levels, parity, and age at abortion between women who used and did not use contraceptives. However, after the current abortion, a significant increase in women who intend to use contraceptives in the future, from 78 to 93%, was observed. A significant reduction in women who do not intend to use contraceptives from 22 to 7.4% was also observed. 59% of women primarily seek knowledge of contraception from healthcare professionals. Among women with a recent live birth, 92% indicated their awareness of contraceptive use as they do not have a plan for the subsequent pregnancy. More than 91% of women discussed contraceptive use with partners. Our survey highlights the importance of education and promotion of the use of contraceptives in developing countries to prevent unintended pregnancy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1723-1729"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alterations in the Hippo Signaling Pathway During Adenogenesis Impairment in Postnatal Mouse Uterus.","authors":"İrem İnanç, Onur Bender, Arzu Atalay, Serdal Kenan Köse, Esra Erdemli","doi":"10.1007/s43032-025-01793-y","DOIUrl":"10.1007/s43032-025-01793-y","url":null,"abstract":"<p><p>The mouse uterus, which consists of single-layered epithelium and undifferentiated mesenchyme at birth, begins to differentiate in the postnatal period. The process of adenogenesis, defined as gland development, begins on the Postnatal (PN) Day 5, and this process is very evident on the PN Day 10. Although various signaling pathways effective in the adenogenesis process but the mechanism underlying this progress have not been clarified yet. Hippo signaling pathway have roles in many cellular functions, such as proliferation, differentiation and cell death. But the relationship between the Hippo signaling pathway and uterus adenogenesis is unknown. The objective of this study has been to determine if there is a change in the Hippo signaling pathway in mice with impaired gland development during the adenogenesis process. To that aim, we use mouse uterus with normal gland development (control group) and gland development inhibited by progesterone (experimental group). Animals were sacrificed on the PN Days 5, 10 and 15. YAP and p-YAP by immunohistochemistry and immunoblotting techniques to identify the main components of Hippo Signaling Pathway. YAP, LATS1, LATS 2, MST1, NF2 and TAZ used for the RT-qPCR methods. In conclusion, Hippo signaling pathway components were reduced during the adenogenesis process in mouse with impaired gland development.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1685-1698"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-05-01Epub Date: 2024-10-01DOI: 10.1007/s43032-024-01695-5
Yanling Han, Lu Shi, Nan Jiang, Jiamin Huang, Xiuzhi Jia, Bo Zhu
{"title":"Dissecting the Single-Cell Diversity and Heterogeneity Underlying Cervical Precancerous Lesions and Cancer Tissues.","authors":"Yanling Han, Lu Shi, Nan Jiang, Jiamin Huang, Xiuzhi Jia, Bo Zhu","doi":"10.1007/s43032-024-01695-5","DOIUrl":"10.1007/s43032-024-01695-5","url":null,"abstract":"<p><p>The underlying cellular diversity and heterogeneity from cervix precancerous lesions to cervical squamous cell carcinoma (CSCC) is investigated. Four single-cell datasets including normal tissues, normal adjacent tissues, precancerous lesions, and cervical tumors were integrated to perform disease stage analysis. Single-cell compositional data analysis (scCODA) was utilized to reveal the compositional changes of each cell type. Differentially expressed genes (DEGs) among cell types were annotated using BioCarta. An assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis was performed to correlate epigenetic alterations with gene expression profiles. Lastly, a logistic regression model was used to assess the similarity between the original and new cohort data (HRA001742). After global annotation, seven distinct cell types were categorized. Eight consensus-upregulated DEGs were identified in B cells among different disease statuses, which could be utilized to predict the overall survival of CSCC patients. Inferred copy number variation (CNV) analysis of epithelial cells guided disease progression classification. Trajectory and ATAC-seq integration analysis identified 95 key transcription factors (TF) and one immunohistochemistry (IHC) testified key-node TF (YY1) involved in epithelial cells from CSCC initiation to progression. The consistency of epithelial cell subpopulation markers was revealed with single-cell sequencing, bulk sequencing, and RT-qPCR detection. KRT8 and KRT15, markers of Epi6, showed progressively higher expression with disease progression as revealed by IHC detection. The logistic regression model testified the robustness of the resemblance of clusters among the various datasets utilized in this study. Valuable insights into CSCC cellular diversity and heterogeneity provide a foundation for future targeted therapy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1502-1519"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-05-01Epub Date: 2025-02-18DOI: 10.1007/s43032-025-01810-0
Portia Cobbinah, Lanting Xiang, Francis Oklah, Xiaojian Yan, Lijiao Hou
{"title":"A Primary Low-Grade Vaginal Extrauterine Endometrial Stromal Sarcoma: A Case Report.","authors":"Portia Cobbinah, Lanting Xiang, Francis Oklah, Xiaojian Yan, Lijiao Hou","doi":"10.1007/s43032-025-01810-0","DOIUrl":"10.1007/s43032-025-01810-0","url":null,"abstract":"<p><p>To analyze the clinical presentation, the diagnostic and therapeutic outcomes of a primary vaginal Low-grade EESS. Managing an LG EESS, such as VESS, is a complex task requiring multi-disciplinary team's involvement. This is crucial to ensure good prognosis due to the non-specific clinical presentations of EESS. A low-grade EESS, such as VESS, requires a multi-disciplinary team to ensure good prognosis. Primary LG-extra-uterine endometrial stromal sarcoma is a rare mesenchymal tumor that can occur at any extra-pelvic site with high recurring rate; therefore, adjuvant therapy such as aromatase inhibitors post-operative is recommended.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1699-1704"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxidative and Endoplasmic Reticulum Stress Mediate Testicular Injury in a Rat Model of Varicocele.","authors":"Lemin Tang, Xinran Guo, Shuman Wen, Zhangyu Duan, Xuansheng Zhong, Meng Liang, Yaping Liao","doi":"10.1007/s43032-024-01749-8","DOIUrl":"10.1007/s43032-024-01749-8","url":null,"abstract":"<p><p>Evidence of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) have been increasingly reported in varicocele (VCL)-affected testes. However, the mechanisms by which oxidative stress (OS) and ER stress contribute to male infertility in VCL remain unclear. In this study, male Sprague-Dawley rats were divided into a control group, which underwent sham surgery, and a VCL group, in which VCL was surgically induced. Eight weeks postoperatively, the VCL group exhibited significant testicular damage and sperm abnormalities. Western blot analysis revealed upregulation of ER stress-related proteins and downstream apoptotic markers in the VCL group. For further investigation, we developed an in vitro oxidative stress model using GC-2 cells treated with 400 µM hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) for 12 h. Cells were also treated with either an ER stress inducer or inhibitor. We found that treatment with H<sub>2</sub>O<sub>2</sub> and the ER stress inducer significantly reduced GC-2 cell viability and increased reactive oxygen species (ROS) production, ER stress, and apoptosis. Conversely, treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects. Our findings suggest a strong association between VCL-induced redox imbalance and ER stress-related injury driven by the UPR in this rat model. Furthermore, 4-PBA effectively reduced germ cell damage induced by ROS-mediated ER stress, offering potential therapeutic insights for treating VCL-related infertility.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1589-1599"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}