Reproductive Sciences最新文献

{"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}

{"title":"Meta-correlation of Sperm Morphology and DNA Fragmentation Index.","authors":"Cennikon Pakpahan, Natasha Susanto Utomo, Markus Christian Hartanto, Marc Torra-Massana, Andri Rezano","doi":"10.1007/s43032-025-01867-x","DOIUrl":"https://doi.org/10.1007/s43032-025-01867-x","url":null,"abstract":"<p><p>The 6th WHO guidelines for human semen examination recommend advanced semen analysis, such as the sperm DNA fragmentation index (DFI), to evaluate male factor infertility, as oxidative stress in the male reproductive system can damage sperm plasma membranes and compromise DNA integrity. Although sperm DFI was known to be associated with pregnancy probability, its examination is often limited by unavailability and high costs. In contrast, basic semen analysis, which includes sperm morphology assessment, is routinely performed, widely available, and cosf-effective. This systematic review and meta-analysis aimed to evaluate the correlation between sperm morphology and DNA Fragmentation Index (DFI) to improve diagnostic and clinical applications. Relevant studies were retrieved from MedLine, Web of Science, Scopus, EBSCO, and ProQuest, using keywords related to the correlation between sperm morphology and DFI. Correlation analyses were conducted using a random-effects model to calculate r-values for normal and abnormal sperm morphology with DFI. This meta-analysis showed an inverse correlation between normal sperm morphology and DFI with r: -0.30 and a positive correlation between abnormal sperm morphology and DFI with r: 0.39. Specifically, the head deformities had stronger correlation with DFI compared to neck and tail deformities. This study underscores the potential to predict DFI from sperm morphology results in settings where DFI testing is unavailable.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026273","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":"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}

{"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}

{"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 (H₂O₂) for 12 h. Cells were also treated with either an ER stress inducer or inhibitor. We found that treatment with H₂O₂ 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}

{"title":"Pancancer Analysis of NSUN2 with a Focus on Prognostic and Immunological Roles in Endometrial Cancer.","authors":"Yuxin Zan, Yan Ding","doi":"10.1007/s43032-024-01625-5","DOIUrl":"10.1007/s43032-024-01625-5","url":null,"abstract":"<p><p>The significance of NSUN2 in carcinogenesis is gradually being recognized, yet a comprehensive analysis across pan-cancer remains a pivotal void in existing research. In our investigation, we capitalized on the UCSC Xena platform to evaluate NSUN2 expression levels and their prognostic implications across a range of cancer types. Furthermore, we employed the cBioPortal database to delve into the genomic variations of NSUN2 within human cancers. Our study encompassed the use of molecular docking, genomic tumor profiling, and an assessment of the gene's responsiveness to pharmacological treatments. Additionally, we utilized algorithmic techniques to measure the relationship between NSUN2 expression and key clinical biomarkers, such as microsatellite instability (MSI), tumor mutational burden (TMB), and immune cell infiltration. Our results have established a notable association between NSUN2 and endometrial cancer (UCEC), thereby confirming its clinical significance through an analysis of tumoral expression patterns, mutational spectra, methylation profiles, and drug sensitivity. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were crucial tools in elucidating the biological roles of NSUN2 in endometrial cancer. Consistently, elevated NSUN2 expression was associated with unfavorable clinical outcomes and was primarily observed in the context of genetic amplifications. Across 22 distinct tumor types, our analysis revealed a notable correlation between NSUN2 expression and various metrics related to immune cell infiltration, tumor stroma, and immune scores. Notably, higher levels of NSUN2 expression have been linked to a reduced response to certain chemotherapeutic agents, including PHA-793887. In UCEC, a positive correlation between NSUN2 methylation and gene expression hints at a potential epigenetic regulatory mechanism underlying cancer progression. Our study highlights the potential of NSUN2 as a key oncogene and its promising role as a therapeutic target as well as a prognostic biomarker for endometrial cancer. This underscores its potential importance in predicting responses to immunotherapy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1459-1476"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427468","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":"Rosiglitazone-Mediated Activation of PPARγ Induces PlGF Expression in Trophoblast Cells.","authors":"Pinki Nandi, Chidambra Halari, Mavis Lee, Elakkiya Prabaharan, Shahil Sarajideen, Dennis K Lee, Sascha Drewlo","doi":"10.1007/s43032-025-01868-w","DOIUrl":"https://doi.org/10.1007/s43032-025-01868-w","url":null,"abstract":"<p><p>Preeclampsia (PE) is a hypertensive pregnancy disorder marked by impaired trophoblast invasion and placental vascular dysfunction, resulting in severe maternal and fetal complications. Placental growth factor (PlGF) is critical for proper placental angiogenesis and is transcriptionally regulated by glial cell missing-1 (GCM1), a downstream effector of peroxisome proliferator-activated receptor-gamma (PPARγ). Decreased PPARγ activity in PE may therefore contribute to diminished PlGF levels, worsening placental pathology. In this study, we investigated the mechanistic role of rosiglitazone, a PPARγ agonist, in rescuing PlGF expression under 1.5% oxygen/reoxygenation stress mimicking PE. Using JEG-3 trophoblast cells, we show that rosiglitazone enhances PPARγ nuclear translocation, leading to increased GCM1 and cyto-protective heme oxygenase-1 (HO-1) expression, and subsequent upregulation of PlGF production under both 21% oxygen and 1.5% oxygen/reoxygenation conditions. Pharmacologic inhibition of PPARγ with T0070907 or siRNA-mediated knockdown abrogated these effects, underscoring PPARγ's essential role in maintaining GCM1-driven PlGF expression. Notably, rosiglitazone treatment rescued PlGF production in 1.5% oxygen/reoxygenation-stressed cells, highlighting a potential therapeutic strategy to mitigate placental dysfunction. These findings define the PPARγ-GCM1-PlGF axis as a mechanistic cornerstone of placental health and suggest that pharmacological activation of PPARγ may offer clinical benefit in improving pregnancy outcomes in PE.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014579","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":"From Dominant Assumptions to Recessive Trait: Rethinking BMP15 in Ovarian Dysfunction.","authors":"Bérénice Hervé, Camille Verebi, Marion Bonnier, Pénélope Jordan, Diana Stroe, Charlotte Voisin, Diane Hill, Cynthia Sarfati, Maud Lansiaux, Daniel Terral, Anne Bachelot, Jean Michel Dupont, Sophie Christin-Maitre, Geneviève Plu-Bureau, Thierry Bienvenu","doi":"10.1007/s43032-025-01831-9","DOIUrl":"https://doi.org/10.1007/s43032-025-01831-9","url":null,"abstract":"<p><p>Approximately 1% of women experience premature ovarian insufficiency (POI) before the age of 40. Genetic factors play a significant role in the development of POI. The BMP15 gene is one of the first genes involved in POI. However, the pathogenicity and the penetrance of BMP15 variants still remain unclear. A cohort of 500 patients with POI/DOR (diminished ovarian reserve) underwent next generation sequencing of the entire coding region of the BMP15 gene. The frequency of each identified BMP15 variant was then compared with that of the general population, taking into account the ethnicity of each individual. Screening of the entire coding region of the BMP15 gene allowed us the identification of 11 different variants, including one pathogenic non-sense variant. A total of 54 patients with POI (10.8%) carried out at least one BMP15 variant. With regard to missense variants, we observed a significant overrepresentation of two missense variants (2/10 missense variants) in our 500 POI patients when compared to the general or specific ethnic subgroups. Of interest is the identification of one homozygous POI subject with a loss-of-function variant. The results of the segregation analysis indicated that this variant was inherited by the healthy mother (menarche at 16 years of age, and physiological menopause at 53 years of age) and by the father. This epidemiological study suggests that the majority of heterozygous missense variants could be considered as benign variants, while the homozygous loss-of-function variant could be considered as pathogenic variant. Several missense variants should be considered as variants of uncertain significance, conferring a moderate risk with probable partial and very low penetrance and/or expressivity. However, it should be noted that these variants are only deleterious in the compound heterozygous or homozygous status.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043061","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}