{"title":"SCM-198 Inhibits EMS Development by Reversing Decreased Proportions of IFN-γ<sup>+</sup>T Cells and CCR5<sup>+</sup>T Cells.","authors":"Yewei Lu, Yunyun Li, Yue Li, Yikong Lin, Xiaolin Wang, Yizhun Zhu, Beihua Wang, Meirong Du","doi":"10.1007/s43032-025-01823-9","DOIUrl":"https://doi.org/10.1007/s43032-025-01823-9","url":null,"abstract":"<p><p>Endometriosis is a common gynecological disease that causes severe pain and infertility. However, the available treatments for EMS are limited. SCM-198, a synthetic form of leonurine, possesses various abilities, including anti-inflammatory, immunomodulatory, antioxidant, anti-fibrotic, and anti-proliferative effects. Previous studies have shown that SCM-198 can inhibit the growth of ectopic lesions, but the specific mechanism remains unknown. The results of our studies indicate that SCM-198 significantly suppresses the endometriotic growth of EMS mice. Enrichment analysis of RNA-seq indicates that SCM-198 is involved in T cell differentiation, activation, cytokine production, stimulation of chemotaxis, and migration. Flow cytometry reveals that SCM-198 reverses the decreased proportions of IFN-γ + T cells and CCR5 + T cells in ectopic lesions. RNA-seq analysis shows that SCM-198 enhances the expression of CCL5 in the ectopic lesions, and western blot is conducted to verify this conclusion both in vivo and in vitro. These findings demonstrate that SCM-198 reverses the decreased proportions of IFN-γ + T cells and CCR5 + T cells, alleviating the growth of mouse ectopic lesions, and the changes in CCR5 + T cells are likely due to the reduced expression of CCL5.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670913","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":"Disruption of the Wnt/β-Catenin and PI3K-AKT-mTOR Crosstalk in Endometrial Stromal Cells: A Case Report of Impaired Decidualization Leading to Recurrent Implantation Failure and Potential Pathway-Specific Therapeutic Interventions.","authors":"Zeyad Hossam Atta Khalil, Omar Altayfa","doi":"10.1007/s43032-025-01832-8","DOIUrl":"https://doi.org/10.1007/s43032-025-01832-8","url":null,"abstract":"<p><p>A 34-year-old woman with a long-standing history of recurrent implantation failure (RIF) and unexplained infertility presented for further evaluation. Molecular analysis revealed a significant disruption in the crosstalk between the Wnt/β-catenin and PI3K-AKT-mTOR signaling pathways, both essential for regulating endometrial receptivity and successful embryo implantation. Immunohistochemical testing showed a marked reduction in β-catenin nuclear translocation and a 65% decrease in AKT phosphorylation, leading to impaired cellular processes such as proliferation and differentiation. This disruption contributed to incomplete decidualization of the endometrium, which played a central role in her repeated implantation failures. Conventional fertility treatments, including hormone therapy and in vitro fertilization (IVF), were ineffective. Consequently, we explored targeted molecular therapies aimed at restoring functionality within these signaling pathways to enhance endometrial receptivity. This case underscores the critical role of the Wnt/β-catenin and PI3K-AKT-mTOR pathways in endometrial function and highlights the potential for novel therapeutic strategies in treating RIF by addressing specific molecular defects.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664466","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}
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":"https://doi.org/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":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziwei Hong, Xinyi Ni, Liying Zhou, Hong Ji, Daowei Yang, Hongshu Sui, Hailong Wang
{"title":"Growth Hormone Improves Ovarian Follicle Health in Premature Ovarian Failure Mice by Reducing Apoptosis : (GH Improves Ovarian Follicle Health in POF Mice by Reducing Apoptosis).","authors":"Ziwei Hong, Xinyi Ni, Liying Zhou, Hong Ji, Daowei Yang, Hongshu Sui, Hailong Wang","doi":"10.1007/s43032-025-01822-w","DOIUrl":"https://doi.org/10.1007/s43032-025-01822-w","url":null,"abstract":"<p><p>Premature ovarian failure (POF) is a perplexing condition in women characterized by cessation of oocyte production in the ovaries. Despite numerous proposed causes for the development of POF, the actual cause of the most POF cases remains unknown. Given that POF significantly affects fertility and is a devastating diagnosis for women, there is an urgent need for the development of new therapies aimed at reducing the long-term health consequences associated with POF. To explore the functions and potential mechanisms of growth hormone (GH) in ovarian development, follicle formation, and oocyte production, we created a mouse model of premature ovarian failure (POF) by administering cisplatin via intraperitoneal injection. Subsequently, we investigated the role of GH in attenuating the POF-induced effects. Our findings demonstrate that GH effectively improves the ovarian coefficient, promotes follicular development, and increases the quantity of oocytes. To explore the functions and potential mechanisms of growth hormone (GH) in ovarian development, follicle formation, and oocyte production, we created a mouse model of premature ovarian failure (POF) by administering cisplatin via intraperitoneal injection. Subsequently, we investigated the role of GH in attenuating the POF-induced effects. Our findings demonstrate that GH effectively improves the ovarian coefficient, promotes follicular development, and increases the quantity of oocytes.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543208","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}
Dimitrios Rafail Kalaitzopoulos, Ursula Catena, Alexandra Kohl Schwartz, Georgios Schoretsanitis, Brigitte Leeners, Panagiotis Drakopoulos, Nicolas Samartzis
{"title":"Correction: Chronic Endometritis and Endometriosis: Two Sides of the Same Coin?","authors":"Dimitrios Rafail Kalaitzopoulos, Ursula Catena, Alexandra Kohl Schwartz, Georgios Schoretsanitis, Brigitte Leeners, Panagiotis Drakopoulos, Nicolas Samartzis","doi":"10.1007/s43032-025-01805-x","DOIUrl":"10.1007/s43032-025-01805-x","url":null,"abstract":"","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"919"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067535","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 : 2025-03-01Epub Date: 2025-02-05DOI: 10.1007/s43032-025-01798-7
Ying Cai, Jing Ma, Shusong Wang, Huaibiao Li
{"title":"Identification of YBX2 and TSKS As STK33 Interacting Proteins in Testicular Germ Cells.","authors":"Ying Cai, Jing Ma, Shusong Wang, Huaibiao Li","doi":"10.1007/s43032-025-01798-7","DOIUrl":"10.1007/s43032-025-01798-7","url":null,"abstract":"<p><p>Spermiogenesis is a unique process, in which round spermatids undergo morphological changes to form spermatozoa. Serine/Threonine Kinase 33 (STK33), a member of the serine/threonine protein kinase family, plays a pivotal role in spermiogenesis, manifested by the infertile phenotype of Stk33 knockout mice and patients carrying STK33 mutations. To date, the mechanism by which STK33 promotes spermiogenesis is not fully understood. Here we aimed to identify germ cell-specific proteins that interact with STK33. Using immunoprecipitation and mass spectrometry, 13 proteins were identified that potentially interact with STK33 in testicular germ cells. By comparing the expression patterns of the candidate genes in testicular germ cells, we selected Y-Box Binding Protein 2 (YBX2) and Testis Specific Serine Kinase Substrate (TSKS) for validation. When co-expressed in cultured cells, TSKS was immunoprecipitated by STK33, and vice versa. Furthermore, STK33 was recruited to the TSKS foci, likely through interaction with TSKS. Although proximity ligation assay demonstrated that STK33 and YBX2 form the complex in germ cells, their interaction was not recapitulated in cultured cells. Phosphorylation assays showed that STK33 was unable to phosphorylate both YBX2 and TSKS in vitro. Overall, these results suggest that STK33 regulates spermiogenesis through TSKS and YBX2, which warrants further investigation in vivo.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"769-782"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256452","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":"Circulating microRNAs in Body Fluid: \"Fingerprint\" RNA Snippets Deeply Impact Reproductive Biology.","authors":"Ayan Mukherjee, Arpana Verma, Troyee Das, Byapti Ghosh, Zhumur Ghosh","doi":"10.1007/s43032-024-01753-y","DOIUrl":"10.1007/s43032-024-01753-y","url":null,"abstract":"<p><p>Circulating miRNAs (C-miRNAs) occuring in a cell-free form within body fluids and other extracellular environments have garnered attention in recent times. They offer deeper insight into various physiological and pathological processes which include reproductive health. This review delves into their diagnostic potential across a spectrum of reproductive disorders, including conditions affecting ovarian function, male infertility and post pregnancy issues. Through analysis of C-miRNA profiles in bodily fluids, researchers uncover crucial markers indicative of reproductive challenges. Dysregulated C-miRNAs emerge as important players in the progression of several reproductive disorders which is the main focus of this review. Advancements in technology, facilitate precise detection and quantification of C-miRNAs, paving the way for innovative diagnostic approaches. Challenges in studying C-miRNAs, such as their low abundance and variability in expression levels, underscore the need for standardized protocols and rigorous validation methods. Despite these challenges, ongoing research endeavors aim to unravel the complex regulatory roles of C-miRNAs in reproductive biology, with potential implications for clinical practice and therapeutic interventions.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"555-574"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807211","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 : 2025-03-01Epub Date: 2024-11-20DOI: 10.1007/s43032-024-01738-x
Fang Hong, Bin Chen, Liu Liu, Xiaomei Tong
{"title":"Successful Live Birth Outcome in A Patient with Empty Follicle Syndrome: A Case Report and Literature Review.","authors":"Fang Hong, Bin Chen, Liu Liu, Xiaomei Tong","doi":"10.1007/s43032-024-01738-x","DOIUrl":"10.1007/s43032-024-01738-x","url":null,"abstract":"<p><p>Here, we report on a rare case of a successful live birth in a patient with empty follicle syndrome. A 35-year-old woman with ovulatory disorder and a 4-year history of primary infertility conducted in vitro fertilization-embryo transfer (IVF-ET) treatment in our hospital. The patient experienced six controlled ovarian stimulation cycles. In the first two cycles, despite adequate ovarian response, normal development of multiple follicles, and normal serum estradiol (E2) levels, no oocytes were retrieved from these mature follicles during the aspiration procedure. The patient was diagnosed with \"empty follicle syndrome\". Whole exome sequencing (WES) identified a missense mutation in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR). In subsequent cycles, we try to increase the trigger dosage, combine gonadotropin-releasing hormone agonists (GnRH agonist) with human chorionic gonadotropin (HCG) for a dual trigger, supplement with luteinizing hormone (LH)-like active substances during the stimulation process, and extend the time between triggering and oocyte retrieval. In the end, successful oocyte retrieval and pregnancy were achieved.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"660-667"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682666","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 : 2025-03-01Epub Date: 2024-07-08DOI: 10.1007/s43032-024-01635-3
Yan Zhuang, Laifu Li, Yanqi Zhang, Xuna Liu, Beibei Zeng, Boxu Zhu, Fei Dai
{"title":"Association between Life's Essential 8 and Infertility as Well as the Mediating Effects of Oxidative Stress and Inflammatory Factors Among U.S. Women Aged 18-45 Years.","authors":"Yan Zhuang, Laifu Li, Yanqi Zhang, Xuna Liu, Beibei Zeng, Boxu Zhu, Fei Dai","doi":"10.1007/s43032-024-01635-3","DOIUrl":"10.1007/s43032-024-01635-3","url":null,"abstract":"<p><p>Management of cardiovascular disease in pregnancy is important, yet the association between cardiovascular health and infertility is rarely reported. In this study, we aimed to explore the association between Life's Essential 8 (LE8), a novel cardiovascular health (CVH) measure, and infertility, and to investigate potential mediating mechanisms. This study investigated cross-sectional data from the 2013-2018 National Health and Nutrition Examination Survey. LE8 score (ranging from 0 to 100) was calculated as the unweighted average of eight CVH metrics. The association between LE8 and infertility was explored through weighted multiple logistic regression. Restricted cubic splines were used to explore nonlinear correlation. In addition, mediation analysis was conducted to investigate the role of oxidative stress and inflammatory markers systematically. After strict exclusion criteria, 1703 American women aged 18-45 years were included. After full adjustment, the LE8 score showed a negative correlation with infertility [per 1 SD increase, OR = 0.675, 95% CI: 0.553-0.824], with a linear dose-response relationship (non-linear P = 0.122). Similar linear negative correlations were found between health factor scores and infertility, with higher body mass index and glucose scores having a significantly lower risk of infertility. Stratified analyses showed a stronger inversed relationship between LE8 and infertility in younger populations. Moreover, mediation analysis revealed that uric acid concentration and lymphocyte count mediated the effect of LE8 on infertility (P < 0.05). LE8 and its subscale scores were linearly and negatively associated with infertility, which may be mediated in part through uric acid and lymphocyte count. Focusing on weight management and glycemic control can effectively reduce the risk of infertility.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"738-747"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559621","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}