Reproductive Sciences最新文献

{"title":"The Role of Endoplasmic Reticulum Stress in Polycystic Ovary Syndrome and Exploration of Potential Therapeutic Targets.","authors":"Yuanyuan Zhang, Yu Wang, Shan Wang, Huiping Zhang","doi":"10.1007/s43032-025-01953-0","DOIUrl":"10.1007/s43032-025-01953-0","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women. In recent years, endoplasmic reticulum (ER) stress has gained increasing attention in the pathogenesis of PCOS. This study aims to explore the potential role of ER stress in PCOS by constructing a predictive model based on ER stress-related genes, and further evaluate the characteristics of immune infiltration and screen potential drugs. Five algorithms, including Lasso, Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Algorithm (XGB), and Generalized Linear Model (GLM), were used to screen key genes associated with PCOS and endoplasmic reticulum (ER) stress. A predictive model was constructed to analyze its diagnostic value in PCOS. External validation of the model was conducted using different datasets to assess its predictive accuracy. Furthermore, immune infiltration analysis was performed to explore the relationship between ER stress-related genes and the immune microenvironment in PCOS, revealing their potential role in disease development through immune response regulation. Finally, molecular docking and drug screening platforms were utilized to identify potential drugs that can modulate the ER stress pathway, providing new drug targets for the clinical treatment of PCOS. Two downregulated genes, NQO1 and NPY, and three upregulated genes, TFEB, JUP, and ATF4, were identified in PCOS cases. The constructed nomogram model demonstrated that the area under the ROC curve for NQO1, TFEB, JUP, NPY, and ATF4 in the validation set were 0.629, 0.600, 0.629, 0.543, and 0.743, respectively, indicating that the PCOS diagnostic model built from these five hub genes has good reliability. Immune infiltration analysis revealed that the expression of the JUP gene was positively correlated with T lymphocyte infiltration, while the expression of TFEB and NPY was negatively correlated with T lymphocyte infiltration, suggesting their potential involvement in immune regulation in PCOS. Through molecular docking and drug screening, 66 potential drugs were identified, 18 of which are already approved for use, providing options for pharmacological treatment of PCOS. The results of this study suggest that endoplasmic reticulum (ER) stress-related genes play an important role in the pathogenesis and development of PCOS, and that accurate predictive models may provide new insights for early diagnosis of the disease. Immune infiltration analysis revealed the potential mechanisms of immune cell involvement in PCOS, while drug screening provides a theoretical basis for future targeted therapies for PCOS.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3127-3140"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856144","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":"SPI1 Transcriptional Activates TXNRD1 to Protect Trophoblast Cell from Ferroptosis.","authors":"Tiantian Chen, Ruxiu Ge, Jie Bai, Haiteng Ye","doi":"10.1007/s43032-025-01945-0","DOIUrl":"10.1007/s43032-025-01945-0","url":null,"abstract":"<p><p>Preeclampsia (PE) is a severe complication of pregnancy characterized by hypertension and organ dysfunction. Abnormal low expression of thioredoxin reductase 1 (TXNRD1) in the placenta has been implicated in the pathogenesis of PE. This study aimed to investigate the role of TXNRD1 in PE and its association with ferroptosis. In our study, placental tissues collected from healthy pregnant women and PE patients, as well as trophoblast cell lines (HTR-8 and JEG-3) were employed in this study. QPCR, Western blot, and immunohistochemistry (IHC) were performed to detect the genes expression. Additionally, ferroptosis level was tested by assessing cell activity, reactive oxygen species (ROS) levels, lipid oxidation, and key ferroptosis-related proteins. The transcriptional regulation mechanism of TXNRD1 was explored using bioinformatics tools, dual luciferase reporter assay, ChIP-qPCR, and electrophoretic mobility shift assay (EMSA). Our results showed that TXNRD1 expression was significantly lower in the placenta of PE patients compared to healthy controls. Consistently, the protein levels of GPX4 and SLC7A11, which are inhibitors of ferroptosis, were reduced in PE, while the levels of COX2 and ACSL4, promoters of ferroptosis, was increased. Overexpression of TXNRD1 in trophoblast cells enhanced ferroptosis resistance, as evidenced by increased cell activity, reduced ROS levels, inhibited lipid oxidation, and altered expression of ferroptosis-related proteins. Conversely, knocking down TXNRD1 exacerbated erastin-induced ferroptosis. Furthermore, we identified SPI1 as a transcriptional activator of TXNRD1, which was also abnormally low expressed in the placenta of PE patients. Overexpression of SPI1 protected trophoblast cells from ferroptosis, which was reversed by inhibiting TXNRD1 expression. Collectively, our findings reveal that SPI1-mediated transcriptional regulation of TXNRD1 plays a protective role in ferroptosis of trophoblast cell, and impeded TXNRD1 expression might involve in PE, advancing our understanding of its pathogenesis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3103-3114"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874963","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":"CHAF1A Promotes Preadipocyte Differentiation and Contributes to Macrosomia in Gestational Diabetes Mellitus.","authors":"Dandan Xia, Xun Xu, Yuhui Zhang, Chenying Zhang, Huiyan Wang","doi":"10.1007/s43032-025-01946-z","DOIUrl":"10.1007/s43032-025-01946-z","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) leads to macrosomia primarily due to fat accumulation caused by adipocyte differentiation. This study aims to investigate the role and underlying mechanisms of Chromatin assembly factor 1 subunit A (CHAF1A) in GDM-induced macrosomia. CHAF1A expression was compared between the GDM with macrosomia group (n = 25) and the normal glucose with normal weight group (n = 15), and the correlation between CHAF1A and neonatal body composition was examined. CHAF1A was overexpressed and knocked down in human visceral preadipocytes (HPA-v), and the effects on cell proliferation and adipogenic differentiation were measured, then the expressions of adipogenic markers were determined. Transcriptome sequencing was employed to investigate the potential mechanisms. Placental immunohistochemistry showed that the expression of CHAF1A in the GDM with macrosomia group was significantly higher than that in the control group (P < 0.05). Correlation analysis showed that CHAF1A expression was positively correlated with neonatal weight, body fat percentage, and fat mass. In functional assays, preadipocytes overexpressing CHAF1A showed enhanced proliferation and adipogenic differentiation, while knockdown of CHAF1A resulted in the opposite effect. Moreover, CHAF1A affected the expression of adipogenic markers. Transcriptome sequencing analysis showed that the differentially expressed genes after CHAF1A silencing were enriched in signaling pathways closely related to preadipocyte differentiation and hormone secretion and synthesis, such as JAK-STAT, Wnt and BMP signaling pathways. CHAF1A promotes the proliferation and differentiation of preadipocytes, which may be a direction for exploring fetal fat accumulation leading to macrosomia in GDM.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3086-3102"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837491","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":"Linking Ghrelin Elevation to Reproductive Dysfunction: Insights from Feed-Restricted Male Rats.","authors":"Marina M Ibrahim, E Seifelnasr, Marwa A Ibrahim, Eman I Hassanen, Asmaa S Morsi, Manal R Bakeer","doi":"10.1007/s43032-025-01943-2","DOIUrl":"10.1007/s43032-025-01943-2","url":null,"abstract":"<p><p>Ghrelin, a peptide hormone consisting of 28 amino acids and primarily produced in the stomach, is crucial for stimulating appetite and maintaining energy balance. Beyond its role in hunger and metabolism, ghrelin also influences the hypothalamic-pituitary-gonadal (HPG) axis, impacting reproductive hormones secretion. During starvation, ghrelin levels increase as part of the body's energy conservation response. The study explored the impact of feed restriction on ghrelin levels and the expression of the ghrelin gene in the gastric fundus, hypothalamus, and testes, as well as their association with reproductive function in adult male rats. Thirty adult male Swiss albino rats were assigned to three groups: a control group (ad libitum feeding), a 30% feed restriction group, and a 60% feed restriction group, over two months. An additional ten adult female rats were included to assess changes in male sexual behavior. Feed restriction resulted in a marked increase in ghrelin levels and its gene expression in the examined tissues, with the most pronounced elevation observed in the 60% feed restricted group. Elevated ghrelin disrupted the HPG axis, leading to reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, while prolactin levels increased. These hormonal changes negatively impacted fertility, libido, semen quality, and overall sexual function. Additionally, feed restrictions caused histopathological alterations in the stomach and testes, along with reductions in both testicular and body weight. These findings suggest that increased ghrelin hormone, in response to energy deficiency, may inhibit the male reproductive axis, linking energy balance and reproductive function in male rats.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3141-3153"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837493","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":"Long Non-Coding, Micro, and Circular RNAs in Ovarian Cancer Metastasis: Pathways and Treatment Approaches.","authors":"Meeral Gosia, Gaurav Doshi, Siddhi Parab, Angel Godad","doi":"10.1007/s43032-025-01948-x","DOIUrl":"10.1007/s43032-025-01948-x","url":null,"abstract":"<p><p>Gynaecologic cancer is a major cause of death for women and the most well-known ovarian cancer (OC) has a high mortality rate. Given that the majority of ovarian cancer deaths are caused by metastatic tumors that have spread to nearby tissues, several biological processes, including angiogenesis and metastasis, have a role in the onset and course of these diseases. Numerous non-coding RNAs (ncRNAs) have been shown in recent studies to contribute to the invasion and metastasis of ovarian cancer by altering particular cellular pathways. Three forms of ncRNAs which are long non-coding RNAs, micro RNAs, and circular RNAs are the subjects of this review. miRNA is used as a potential biomarker such as miR-375 which is a serum exosome and also in therapeutics. lncRNA sponges with miRNA which sequesters and regulates tumor progression such as XIST miR-149-3p. circRNA targets proteins and regulates gene expression. This review provides an overview of the precise function of non-coding RNAs in the many pathways and molecular exchanges that contribute to the invasion and metastasis of malignancies. To increase the survival rate of OC patients, new approaches to ncRNA-targeted therapy are being utilised, including targeting lncRNAs and circRNAs and modulating the tumor microenvironment using exosomes.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2842-2863"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856143","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":"Utilization of MSC-Derived Extracellular Vesicles and Bioscaffolds in Enhancing Oocyte In Vitro Maturation and Culture: A Review.","authors":"Maryam Mehravar, Maryam Salimi, Mahsa Kazemi, Mohammad Majidi, Elham Roshandel, Hamid Nazarian","doi":"10.1007/s43032-025-01889-5","DOIUrl":"10.1007/s43032-025-01889-5","url":null,"abstract":"<p><p>Failure in germ cells development and oocyte maturation remains a significant challenge in assisted reproductive technologies (ART) and can lead to feltilization failure and poor embryo quality. Rescue in vitro maturation (R-IVM) offers a promising approach to improve the reproductive outcomes in such cases. Mesenchymal stem cells-derived exosomes, have demonstrated therapeutic potential for both oocytes and granulosa cells. However, their effects on immature oocytes under R-IVM remain largely unexplored. Furthermore, incorporating exosomes into bioscaffolds may provide controlled release system, enhancing stability within IVM and in vitro culture (IVC) environments. This review evaluates the current evidence regarding the effects of MSC-derived exosomes on oocyte and granulosa cell function and explores the potential of exosome-loaded scaffolds to optimize IVM outcomes, offering new strategies for enhanced reproductive success. Recent findings indicate that bioscaffolds composed of appropriate polymers with high exosome encapsulation efficiency and a release window of 24-48 h can mimic the in vivo environment and support the maturation of oocytes and embryos in IVM/IVC systems.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2829-2841"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718353","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":"CHIR99021 Enhances the Proliferation of Mouse Female Germline Stem Cells Via Modulating ERCC2.","authors":"Qingling Jia, Geng G Tian, Xiaoyong Li, Ji Wu","doi":"10.1007/s43032-025-01877-9","DOIUrl":"10.1007/s43032-025-01877-9","url":null,"abstract":"<p><p>Female germline stem cells (FGSCs) are a type of adult stem cell that exist in mammalian ovaries and can self-renew and differentiate into mature oocytes. Small molecule compounds are substances with a molecular weight less than 900 Daltons that can affect cellular functions and behaviors through various mechanisms. Here, we identified three compounds, Agrin, CHIR99021 (CHIR), and Testosterone, that can enhance the proliferation of FGSCs, with CHIR demonstrating superior efficacy. To elucidate the mechanism underlying CHIR's role in promoting FGSCs proliferation, we conducted RNA sequencing and tandem mass tag (TMT)-based quantitative proteomic profiling on FGSCs both with and without CHIR exposure. By integrating the data from these two sequencing approaches, we employed gene set enrichment analysis (GSEA) and identified Ercc2 as a crucial gene modulated by CHIR-induced FGSC proliferation. Further experiments confirmed that CHIR enhanced FGSCs proliferation via ERCC2. This research deepens our comprehension of the proliferative mechanisms of FGSCs and lays a theoretical foundation for future investigations into the developmental mechanisms of female germ cells, as well as the development of infertility treatments.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3166-3178"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174637","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":"Preeclampsia is Associated with Altered Expression of Ferroptosis Biomarkers in Placental but not Maternal Vasculature.","authors":"Shu-Wing Ng, Allen C Ng, Michelle C Ng, Shu-Kay Ng, Felice Arcuri, Elizabeth M Genega, Jaclyn C Watkins, Drucilla J Roberts, Michael D House, Perrie F O'Tierney-Ginn, Daniel P Jacobsen, Anne C Staff, Errol R Norwitz","doi":"10.1007/s43032-025-01935-2","DOIUrl":"10.1007/s43032-025-01935-2","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent mechanism of programmed cell death, has been implicated in the pathogenesis of preeclampsia (PE). Here, we investigate the expression of key ferroptosis biomarkers in placental and decidua basalis tissues. Immunohistochemical (IHC) staining showed high expression of the ferroptosis suppressor, ferroptosis-suppressor protein 1 (FSP1), and the end product malondialdehyde (MDA), in healthy CD31-positive placental endothelium. The staining of all three markers was significantly reduced in PE placentas (P = 0.028). In vitro studies showed that an immortalized endometrial endothelial cell line, and its fetal counterpart, human umbilical vein endothelial cells, are intrinsically highly resistant to erastin-induced ferroptotic cell death compared with trophoblast, endometrial epithelial, and stromal fibroblast cell types. FSP1 was specifically expressed in the endometrial endothelial cells. Both FSP1 and another ferroptosis suppressor protein, GPX4, were degraded when the cells underwent ferroptotic cell death. Interestingly, staining of these same markers in maternal decidua basalis tissues did not show endothelium-specific staining, and no significant difference in staining was noted between healthy and PE tissues. Since previous studies have shown that endometrial cells can activate ferroptosis to produce pro-angiogenic cytokines, we posit that healthy placental endothelial cells activate ferroptosis, as evidenced by high MDA, to promote vasculature development without undergoing cell death, whereas PE placentas show reduced ferroptosis and vasculature underdevelopment. In contrast, both healthy and PE decidua basalis tissues were considered to be in a resting stage with regard to ferroptosis. Further studies are warranted to investigate how ferroptosis is regulated in both healthy and PE pregnancies.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3074-3085"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795228","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":"Melatonin Protects against LPS-Induced Mitochondrial Dyshomeostasis and Ovarian Damage through JNK Signaling Pathway in Mouse Ovary.","authors":"Ling-Ge Shi, Si-Min Ding, Tong-Kun Guo, Peng Chen, Shuang-Shuang Cui, Zhuo-Nan Yang, Mengyao Wang, Rui Wang, Dongmei Ji, Tao Zhang, Dan Liang, Lili Wang, Yunxia Cao, Yajing Liu","doi":"10.1007/s43032-025-01954-z","DOIUrl":"10.1007/s43032-025-01954-z","url":null,"abstract":"<p><p>Both mitochondrial dysfunction and inflammation are closely associated with the pathogenesis of diminished ovarian reserve (DOR). While melatonin (MT) is known to protect against ovarian injury, its precise mechanism in counteracting lipopolysaccharide (LPS)-induced mitochondrial dysfunction and ovarian reserve impairment remains unclear. This study aimed to explore the effects and underlying mechanisms of MT on LPS-induced ovarian reserve dysfunction. Follicle development in mouse models was assessed using HE staining and follicle counting. Immunofluorescence, Western blotting, and quantitative real-time PCR were employed to investigate the biological mechanisms by which MT protects the ovary. The levels of reactive oxygen species (ROS) and mitochondrial function in KGN cells were evaluated using H2DCFDA and TMRE staining. The findings revealed that LPS stimulation led to reduced expression of anti-Mullerian hormone (AMH) and growth differentiation factor 9 (GDF9), indicating impaired ovarian function. Treatment with MT countered these effects. Immunofluorescence analysis demonstrated that MT alleviated LPS-induced follicular depletion and modulated the expression levels of mitochondrial dynamics-related proteins OPA1 and DRP1. Additionally, LPS exposure induced excessive autophagy, elevated ROS levels, and heightened inflammation but did not significantly affect cell cycle progression or apoptosis. Notably, MT rescued the suppression of the JNK pathway caused by LPS stimulation. In summary, our results indicate that MT effectively restores the balance between mitochondrial fusion and fission, enhances ovarian reserve function via activation of the JNK signaling pathway, suppresses inflammation and autophagy, and ultimately improves overall ovarian function.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3154-3165"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837494","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":"Investigation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell and Melatonin Treatment in Premature Ovarian Failure Model.","authors":"Aytaj Jafarzade, Elvan Anadol, Muzaffer Çaydere, Durmuş Burgucu, Canan Yılmaz, Semih Ergişi, Tamer Mungan","doi":"10.1007/s43032-025-01942-3","DOIUrl":"10.1007/s43032-025-01942-3","url":null,"abstract":"<p><p>Premature Ovarian Insufficiency (POI) may develop in young female patients due to chemotherapy treatments, which causes infertility. In addition to stem cell treatment, which is an effective method for POI in recent years, melatonin, which has high antioxidant properties, is also known to be effective. This study aimed to investigate the efficacy of melatonin, human umbilical cord-derived mesenchymal stem cell (hucMSC), and melatonin + human umbilical cord-derived mesenchymal stem cell (hucMSC) treatments on POI in cyclophosphamide-induced POI models in rats. Sixty female animals were included in the experiment and randomly divided into the control, cyclophosphamide, cyclophosphamide + melatonin, cyclophosphamide + hucMSC, and cyclophosphamide + hucMSC + melatonin groups. Except for the control group, the POI model was created by administering intraperitoneal cyclophosphamide to other groups. Afterward, half of the animals were euthanized to investigate the effectiveness of the treatment, and AMH, E2, FSH, LH values in the blood of the euthanized animals were investigated by ELISA method. Follicle count was conducted in ovarian tissues, and the rate of apoptosis was determined by caspase-3 immunostaining. Fertility test was conducted on the group without euthanasia, and the number of baby rats was compared. Post-treatment E2 and AMH values were at the highest level in the cyclophosphamide + hucMSC + melatonin group. FSH value was at the lowest level in the cyclophosphamide + hucMSC + melatonin group. No significant difference was found between the groups in terms of LH value. Recovery was achieved with treatment in all follicle development stages. Particularly, the number of secondary and Graff follicles was statistically significantly higher in the cyclophosphamide + hucMSC + melatonin group. In caspase-3 immunostaining, the highest level of apoptosis was observed in the cyclophosphamide group, while the highest level of recovery was seen in the cyclophosphamide + hucMSC + melatonin group. As a result of fertility, the highest number of babies was observed in the cyclophosphamide + hucMSC + melatonin group following POI treatment. This study revealed that the success rate of POI treatment increases not only with stem cell treatment but also with combined treatment. If stem cell treatments are combined with melatonin with strong antioxidant properties, not as mono-therapy, for the purpose of infertility treatment, the effectiveness of the treatment increases.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2985-2996"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856142","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}