Reproductive Sciences最新文献

{"title":"Menstrual Blood-Derived Endometrial Stem Cells Ameliorate Ovarian Senescence by Relieving Oxidative Stress-Induced Inflammation.","authors":"Haofeng Song, Ruiyun Zhang, Yinglei Liu, Jie Wu, Wenqiang Fan, Junfang Wu, Yanli Liu, Juntang Lin","doi":"10.1007/s43032-024-01739-w","DOIUrl":"10.1007/s43032-024-01739-w","url":null,"abstract":"<p><p>Senescence is a degenerative process that occurs with ageing, and in the female reproductive system, senescence occurs earlier in the ovaries than in other tissues and organs, which implies a decrease in oocyte quality and exhaustion of the primordial follicular pool, leading to impaired ovarian function and an inability to maintain normal fertility. Unfortunately, the development of curative and effective treatments for ovarian senescence is still a considerable challenge. Currently, mesenchymal stem cells (MSCs)-based therapies for treating various refractory diseases, especially ovarian dysfunction, have been extensively studied and confirmed. However, the mechanisms by which MSCs improve ovarian senescence are not yet clear. Therefore, in this study, a mouse ageing model was generated via the intraperitoneal injection of a D-galactose (D-gal) solution, and the effects of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on the ovarian follicle count, fibrosis level, and degree of apoptosis were evaluated. Subsequently, an ovarian granulosa cell ageing model was induced with H₂O₂, and CCK-8 assays, flow cytometry, mitochondrial membrane potential analysis and Western blotting were subsequently performed to further investigate the potential mechanism by which MenSCs ameliorate cellular oxidative damage. Overall, our findings demonstrated that MenSCs treatment can increase the cellular antioxidant capacity by activating the NRF2/HO-1 signalling pathway and further ameliorate the inflammatory ovarian microenvironment, apoptosis and dysfunction in ageing mice. These results provide reliable evidence and support for MenSCs-based therapy for ovarian senescence.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1566-1579"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584170","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":"Circ_0015382 Regulates the miR-942-5p/NDRG1 Axis to Suppress Trophoblast Cell Functions.","authors":"Haiyan Wu, Lijuan Zhao","doi":"10.1007/s43032-024-01685-7","DOIUrl":"10.1007/s43032-024-01685-7","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are non-coding RNAs that exert vital function in many human diseases, including preeclampsia (PE). Circ_0015382 is considered to be a key regulator of PE progression, so more molecular mechanisms need to be further studied. Real-time quantitative PCR was used to detect the mRNA levels of circ_0015382, miR-942-5p, and N-myc downstream regulated 1 (NDRG1). Western blot analysis was conducted to assess the protein levels. MTT and EdU assays were used to assess cell proliferation. Cell invasion was analyzed by transwell assay. Tube formation assay was conducted to detect cell angiogenesis. Dual-luciferase reporter assay and RNA immunoprecipitation were used to analyze the target relationship between miR-942-5p and circ_0015382 or NDRG1. Our data showed that circ_0015382 and NDRG1 were up-regulated, while miR-942-5p was down-regulated in the placental tissues of PE patients. Trophoblast cell proliferation, invasion, and angiogenesis were promoted by knockdown of circ_0015382. Circ_0015382 could sponge miR-942-5p, and NDRG1 was a target of miR-942-5p. MiR-942-5p inhibitor could reverse the promoting effects of si-circ_0015382 on trophoblast cell functions. Besides, the enhancing effects of miR-942-5p mimic on trophoblast cell proliferation, invasion, and angiogenesis could be eliminated by NDRG1 overexpression. In conclusion, our data showed that circ_0015382 inhibited trophoblast cell proliferation, invasion, and angiogenesis through regulating miR-942-5p/NDRG1 axis, providing a new mechanism for the regulation of PE progression.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1491-1501"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361951","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":"A Compound Heterozygous Pathogenic Variant in ZP2 Gene Causes Female Infertility.","authors":"Shulin Yang, Zongzhe Li, Xinling Ren, Jing Yue","doi":"10.1007/s43032-024-01729-y","DOIUrl":"10.1007/s43032-024-01729-y","url":null,"abstract":"<p><p>The oocyte maturation defect 6 is an autosomal recessive hereditary disease caused by a homozygous variant in ZP2 gene. It is characterized by female primary infertility due to an abnormally thin zona pellucida (ZP) and defective sperm binding. Here we identified a compound heterozygous variant (c.1924C > T and c.1695-2A > G) in ZP2 gene in a Chinese Han family. Quantitative real-time PCR showed that the variant c.1924C > T significantly decreased the expression of truncated ZP2 message RNA by the nonsense-mediated decay pathway. Minigene assays showed the c.1695-2A > G variant led to an extra-61-nt preservation of intron 15 at the junction between exons 15 and 16 during transcription. Both variants (c.1924C > T and c.1695-2A > G) resulted in truncated ZP2 proteins (p.R642X and p.C566Hfs*2) that lost the transmembrane domain, which prevented the secretion of the mutant ZP2 proteins and produced a structurally abnormal ZP, thus resulting in female infertility. This study further elucidated the pathogenic mechanism of these two variants and provided new support for the genetic diagnosis of female infertility.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1557-1565"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506825","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":"The Differentiation Fate of Granulosa Cells and the Regulatory Mechanism in Ovary.","authors":"Yilin Chen, Shimeng Wang, Chunping Zhang","doi":"10.1007/s43032-024-01682-w","DOIUrl":"10.1007/s43032-024-01682-w","url":null,"abstract":"<p><p>Granulosa cells (GCs) are important drives of the reproductive process, not only the supporting cells for nutrition, but also cells with endocrine functions. Their differentiation and development parallel the entire menstruation period and even during pregnancy, making it tightly linked to the fate of the follicle. To elucidate the underlying mechanism is of great significance for related researches. The life course of GCs is briefly divided into five stages, from epithelial cells to pre-granulosa cells, GCs, mural and cumulus cells, lutein cells, and eventually disappear. A wide variety of genes and transcription factors participate in the regulation of different stages, and more importantly, various hormones secreted by the pituitary gland and GCs themselves play a leading role. These endogenous and exogenous signalling molecules interact to form a cross-linked communication network, promoting the development of GCs. Together with oocytes, theca cells and other functional cells in the ovary, GCs drive one of the most vital biological processes in women.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1414-1426"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081413","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":"Screening of Oxidative Stress-related Biomarkers and Antioxidant Drugs for Polycystic Ovary Syndrome Based on Bioinformatics and Molecular Docking.","authors":"Lanhui Chen, Tian Li, Jialiang Xu, Siqi Liao, Haocheng Xu, Kun Li, Deyana Ivanova, Yuewen Si, Xin Zhang, Jianning Zhang, Fangfang Li, Xuemei Chen, Yingxiong Wang, Biao Xie, Dan Shi, Meijiao Wang","doi":"10.1007/s43032-025-01790-1","DOIUrl":"10.1007/s43032-025-01790-1","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of reproductive age. Oxidative stress (OS) is suggested to play a significant role in the development of PCOS. Using antioxidants to reduce OS and maintain a healthy balance in the body could be a novel treatment approach for PCOS. This study analyzed transcriptome data from the Gene Expression Omnibus database, focusing on genes associated with OS. By implementing two machine learning algorithms, three OS-related biomarkers-HMOX1, MMP9, and KLF2-were successfully identified. To evaluate the diagnostic potential of these biomarkers, a Logistic regression model was employed. Additionally, granulosa cells were collected from healthy individuals and infertile women with PCOS, and the reliability of HMOX1, MMP9, and KLF2 was verified by quantitative real-time PCR experiments. Furthermore, small molecule drugs targeting proteins encoded by genes HMOX1 and MMP9 were predicted through the Drug Signature Database. Molecular docking of drugs to proteins identified two antioxidants, butein and demethoxycurcumin, as potential candidates for PCOS therapy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1644-1660"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060604","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":"Increased Trophoblast Cell Ferroptosis via HMGB1/ACSL4 Pathway Is Associated with Spontaneous Abortion.","authors":"Yishan Dong, Yong Li, Wenjie Tang, Qin Chen, Chengcai Kong","doi":"10.1007/s43032-025-01817-7","DOIUrl":"10.1007/s43032-025-01817-7","url":null,"abstract":"<p><strong>Introduction: </strong>Trophoblast cells undergo ferroptosis in pregnancy-related diseases. HMGB1 participates in pathological ferroptosis. However, whether lipopolysaccharide (LPS) -mediated HMGB1 expression induces the ferroptosis of trophoblast cells and further spontaneous abortion (SA) remains unknown.</p><p><strong>Methods: </strong>HMGB1 and ACSL4 expression were measured in villous tissues from 20 women with SA and 20 women with elective abortion. Human HTR-8/SVneo cells were treated with LPS to establish an in vitro abortion model. The hallmarks of ferroptosis including MDA, GSH, Fe²⁺ and ROS were detected using indicated assay kits.</p><p><strong>Results: </strong>The levels of HMGB1 and ACSL4 in villous tissues from SA women were significantly higher than those in the normal control group. HMGB1 interacts with and stabilizes ACSL4 to promote the ferroptosis of trophoblast cells. Conversely, HMGB1 and/or ACSL4 inhibition attenuated LPS-induced trophoblast cells ferroptosis.</p><p><strong>Conclusions: </strong>An HMGB1/ACSL4 axis is engaged in LPS-induced ferroptosis of trophoblast cells, and may be targeted to design treatments preventing SA.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1713-1722"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493402","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":"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}

{"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}

{"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}

{"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}