Reproductive Sciences最新文献

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Investigation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell and Melatonin Treatment in Premature Ovarian Failure Model. 脐带间充质干细胞联合褪黑素治疗卵巢早衰模型的疗效研究。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-14 DOI: 10.1007/s43032-025-01942-3
Aytaj Jafarzade, Elvan Anadol, Muzaffer Çaydere, Durmuş Burgucu, Canan Yılmaz, Semih Ergişi, Tamer Mungan
{"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}
引用次数: 0
Luteinizing Hormone Preserves Oocyte-Granulosa Cell Communication in Growing Follicles Exposed to Chemotherapy with Alkylating Agents at the Primordial Stage in a Mouse Model. 在小鼠模型中,黄体生成素在原始阶段暴露于烷基化药物化疗的生长卵泡中保持卵母细胞-颗粒细胞的通讯。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 10.1007/s43032-025-01936-1
Luis Miguel Del Castillo, Noelia Ramírez-Martín, María José Soriano, Jessica Martínez, Nuria Pellicer, Antonio Pellicer, Sonia Herraiz
{"title":"Luteinizing Hormone Preserves Oocyte-Granulosa Cell Communication in Growing Follicles Exposed to Chemotherapy with Alkylating Agents at the Primordial Stage in a Mouse Model.","authors":"Luis Miguel Del Castillo, Noelia Ramírez-Martín, María José Soriano, Jessica Martínez, Nuria Pellicer, Antonio Pellicer, Sonia Herraiz","doi":"10.1007/s43032-025-01936-1","DOIUrl":"10.1007/s43032-025-01936-1","url":null,"abstract":"<p><p>Reciprocal communication between the oocyte and adjacent granulosa cells (GC) throughout folliculogenesis can be disrupted by chemotherapy. Recent work suggests that luteinizing hormone (LH) may protect the quality of metaphase-II oocytes derived from primordial follicles exposed to chemotherapy in mice. Here, we showed that LH improved the follicular yield of CD1 mice ovaries exposed to alkylating chemotherapy by primarily protecting the smallest follicles, i.e., the primordial and primary populations. LH treatment reverted the chemotherapy-induced impairment of oocyte-GC communication at the gene and protein levels in secondary and later-stage follicles exposed to alkylating chemotherapy at the primordial phase by preserving the germ and somatic cell compartments. These changes are follicle-specific, as supported by the absence of differences in ovarian stroma. LH also restored the immunofluorescence signal for cell junction proteins Cx37, E-Cad and Cx43, and for oocyte-secreted factors GDF9 and BMP15. The alteration of signal intensity associated with these cell junction proteins and oocyte-secreted factors by chemotherapy was detected beyond the secondary stage, suggesting that attenuation of oocyte-GC crosstalk might happen during the primary-secondary transition. Our results suggest that LH-treated primordial follicles retain the ability to properly establish oocyte-GC interactions and crosstalk during follicular growth representing a novel mechanism triggered by LH that would explain the reported protective effects of LH on oocyte quality and female fertility. However, this is an animal model study that should be validated in larger studies with human samples.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3115-3126"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795227","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}
引用次数: 0
MyD88 Signaling in Sertoli Cells Mediates LPS-Induced Orchitis in Mice. 支持细胞MyD88信号介导lps诱导的小鼠睾丸炎。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-13 DOI: 10.1007/s43032-025-01955-y
Yuchuan Luo, Chang Yan, Jing Wang, Chenjun Wang, Hongji Yu, Xintong Yin, Yingjie Wu, Ning Liu, Yinghe Qin
{"title":"MyD88 Signaling in Sertoli Cells Mediates LPS-Induced Orchitis in Mice.","authors":"Yuchuan Luo, Chang Yan, Jing Wang, Chenjun Wang, Hongji Yu, Xintong Yin, Yingjie Wu, Ning Liu, Yinghe Qin","doi":"10.1007/s43032-025-01955-y","DOIUrl":"10.1007/s43032-025-01955-y","url":null,"abstract":"<p><p>Orchitis, a prevalent male reproductive disorder that can severely impair fertility and potentially result in infertility. Sertoli cells orchestrate testicular immune responses during orchitis by modulating local inflammation and maintaining blood-testis barrier integrity. While Myeloid differentiation primary response protein 88 (MyD88), a critical adaptor molecule in the TLR4 signaling pathway, is known to mediate immune responses, its cell-specific role in Sertoli cells during lipopolysaccharide (LPS)-induced orchitis remains elusive. Using an murine orchitis model established through intraperitoneal LPS administration, we observed pronounced testicular inflammation concurrent with dramatic upregulation of MyD88 protein levels (P < 0.05). To further investigate the Sertoli cell-specific function of MyD88, we generated conditional Myd88 knockout (cKO) mice. Compared to controls, cKO mice showed marked attenuation of testicular edema along with improved sperm motility and viability post-LPS challenge. Myd88 deletion also suppressed LPS-triggered surges in pro-inflammatory cytokines (TNF-α, IL-6), maintained seminiferous tubule architecture, and mitigated neutrophil infiltration. Further studies demonstrated that Myd88 deletion rescued LPS-induced BTB disruption by restoring the expression of key BTB components (Connexin43, Claudin-11). Additionally, NF-κB signaling pathway is activated by MyD88 mediated inflammatory responses. Collectively, these findings uncover Sertoli cell specific MyD88 as a key regulator in LPS-induced orchitis pathogenesis, highlighting its potential as a promising therapeutic target for orchitis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3013-3024"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837495","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}
引用次数: 0
Effects of Carnitine and Coenzyme Q10 on Sperm Quality and Pregnancy Rates in Men with Unexplained Infertility: A Systematic Review and Network Meta-Analysis. 肉碱和辅酶Q10对不明原因不孕症男性精子质量和妊娠率的影响:系统综述和网络荟萃分析
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-14 DOI: 10.1007/s43032-025-01958-9
Changmin Niu, Xueyu Lu, Yue Xie, Yawen Yu, Yuxin Gao, Nuo Shen, Ying Zheng
{"title":"Effects of Carnitine and Coenzyme Q10 on Sperm Quality and Pregnancy Rates in Men with Unexplained Infertility: A Systematic Review and Network Meta-Analysis.","authors":"Changmin Niu, Xueyu Lu, Yue Xie, Yawen Yu, Yuxin Gao, Nuo Shen, Ying Zheng","doi":"10.1007/s43032-025-01958-9","DOIUrl":"10.1007/s43032-025-01958-9","url":null,"abstract":"<p><strong>Aims: </strong>To study and explore the effects of oral Carnitine and Coenzyme Q10 on the quality of sperm and the rate of pregnancy in males with unexplained infertility.</p><p><strong>Background: </strong>Preventing and reducing oxidative stress is essential for male infertility treatment. Antioxidants can effectively improve sperm quality and maintain sperm motility, thereby improving male fertility. At present, the most commonly used antioxidants in the clinic are carnitine and coenzyme Q10.</p><p><strong>Design: </strong>A systematic review and network meta-analysis.</p><p><strong>Methods: </strong>In this study, the effects of carnitine and coenzyme Q10 antioxidants on sperm quality and the rate of pregnancy in men with unexplained infertility were explored using a network meta-analysis method. The Cochrane Library, EMBASE, Web of Science and PubMed databases were searched for relevant studies. The observed indicators included semen concentration, progressive sperm motility, the rate of morphologically normal sperm and pregnancy rate.</p><p><strong>Results: </strong>16 pieces of literature were included after rigorous screening. L-carnitine, coenzyme Q10 and L-carnitine + acetyl-L-carnitine significantly improved sperm quality parameters compared with placebo. CoQ10 induced the highest increase in sperm concentration (SMD 2.98 [95% CI: 1.13 to 7.87]). Furthermore, L-Carnitine has the greatest improvement effect on progressive sperm motility (SMD 4.19 [95% CI: 1.60 to 10.95]).</p><p><strong>Conclusions: </strong>CoQ10 was the most effective intervention measure for improving sperm concentration, and L-carnitine was regarded as the best treatment method for enhancing sperm motility. In the future, we need more high-quality and large-sample studies to verify the effectiveness of antioxidants in the treatment of male infertility.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2864-2876"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856141","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}
引用次数: 0
Endometrial Mesenchymal Stem Cell-Derived Exosomal miR-4669 Promotes EMT in Adenomyosis by Inducing M2 Macrophage Polarization via the DUSP6/ERK Pathway. 子宫内膜间充质干细胞来源的外泌体miR-4669通过DUSP6/ERK通路诱导M2巨噬细胞极化,促进子宫腺肌症中的EMT。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 10.1007/s43032-025-01944-1
Yingying Qiu, Xinjun Wei, Jian Cao, Jindan Wang, Qianru Dou, Fangfang Zhou, Xi Chen, Yongli Liu, Guiping Wan, Meihua Huang, Zhenli Li, Tao Gui
{"title":"Endometrial Mesenchymal Stem Cell-Derived Exosomal miR-4669 Promotes EMT in Adenomyosis by Inducing M2 Macrophage Polarization via the DUSP6/ERK Pathway.","authors":"Yingying Qiu, Xinjun Wei, Jian Cao, Jindan Wang, Qianru Dou, Fangfang Zhou, Xi Chen, Yongli Liu, Guiping Wan, Meihua Huang, Zhenli Li, Tao Gui","doi":"10.1007/s43032-025-01944-1","DOIUrl":"10.1007/s43032-025-01944-1","url":null,"abstract":"<p><p>Adenomyosis (AM), a gynecological disorder that severely affects female reproductive health. AM-associated macrophage (AAM) polarization-induced epithelial-mesenchymal transition (EMT) is a key driver of AM progression. In this study, we investigated the role and underlying mechanisms of endometrial mesenchymal stem cell (eMSC)-derived exosomes in regulating AAM polarization and the subsequent EMT of endometrial epithelial cells (EECs). In vitro coculture studies revealed that AM eutopic eMSCs markedly induced M2 macrophage polarization via exosomes and promoted EMT of EECs. Differentially expressed microRNAs (DE-miRNAs) between exosomes derived from normal eMSCs (N-eMSCs) and AM eutopic eMSCs (A-eMSCs) were identified using miRNA sequencing and miR-4669 was found to be the most significantly upregulated miRNA. Internalization of exosomal miR-4669 by macrophages induced their polarization toward the M2 phenotype and promoted the EMT of EECs. Mechanistic analysis using luciferase assay, mRNA sequencing, and rescue experiments revealed that miR-4669 induced M2 macrophage polarization via downregulation of DUSP6 and activation of MAPK/ERK signaling. The polarized M2 macrophages promoted the EMT of ISK cells via TGF-β1 secretion. In an AM xenograft mouse model, miR-4669 depletion inhibited AM progression by targeting the DUSP6/ERK1/2 pathway in macrophages. Overall, AM A-eMSC-derived exosomal miR-4669 facilitates M2 macrophage polarization by targeting the DUSP6/ERK signaling pathway, thereby promoting EMT of EECs via TGF-β1 secretion. These findings open avenues for developing novel preventive and therapeutic strategies for AM.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2922-2945"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795226","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}
引用次数: 0
Dimethyl Fumarate Improves Diabetic Erectile Dysfunction in Rats via Nrf2-Mediated Suppression of Penile Endothelial Oxidative Stress. 富马酸二甲酯通过nrf2介导的阴茎内皮氧化应激抑制改善糖尿病大鼠勃起功能障碍。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-18 DOI: 10.1007/s43032-025-01956-x
Seçkin Engin, Elif Nur Barut, Yeşim Kaya Yaşar, İlyas Ay, Sena F Sezen
{"title":"Dimethyl Fumarate Improves Diabetic Erectile Dysfunction in Rats via Nrf2-Mediated Suppression of Penile Endothelial Oxidative Stress.","authors":"Seçkin Engin, Elif Nur Barut, Yeşim Kaya Yaşar, İlyas Ay, Sena F Sezen","doi":"10.1007/s43032-025-01956-x","DOIUrl":"10.1007/s43032-025-01956-x","url":null,"abstract":"<p><p>Diabetic erectile dysfunction (DMED) is a prevelant urological complication in diabetic men. Increased oxidative stress accompanied with diminished Nrf2 antioxidant pathway has been shown to impair NO/cGMP signaling and distrupt the penile vascular endothelial function in DMED. The present study aimed to investigate the therapeutic effect of dimethyl fumarate (DMF), a clinically approved Nrf2 activator used for psoriasis and multiple sclerosis, in a rat model of streptozotocin (STZ)-induced DMED. Male Sprague Dawley rats were injected with a single intraperitoneal dose of STZ (60 mg/kg) to induce DMED. At week 8, both diabetic and nondiabetic rats were treated orally with DMF (25 or 100 mg/kg) or vehicle for 4 weeks. At week 12, erectile function was evaluated by measuring the intracavernosal pressure (ICP) responses to the electrical stimulation of cavernous nerves. Penile tissues were collected for biochemical and molecular analysis. DMED occurred in diabetic rats, evidenced by reduced the maximum ICP/ mean arterial pressure (MAP) and total ICP/MAP ratios. The penile tissues of diabetic rats exhibited increased MDA level along with decreased Nrf2 and HO-1 protein levels, SOD and CAT activities, and reduced phosphorylated eNOS at serine 1177 and phosphorylated VASP at serine 239. Treatment with DMF at 100 mg/kg was effectively reversed these functional reponses and tissue biochemical alterations in DMED rats. This study provides the first evidence that DMF improved DMED by alleviating oxidative stress and endothelial dysfunction via the activation of Nrf2 antioxidant pathway, suggesting a potential clinical repurposing of DMF for DMED.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3025-3037"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874927","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}
引用次数: 0
The Effect of Music and Mandala Activity on Stress and Stress-Coping Levels of Infertile Women Who Had an Embryo Transfer: A Randomized Clinical Trial. 音乐和曼陀罗活动对胚胎移植不孕妇女压力和压力应对水平的影响:一项随机临床试验。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-07 DOI: 10.1007/s43032-025-01891-x
Banu Şişli, Kerime Derya Beydağ, Aysu Yıldız Karaahmet
{"title":"The Effect of Music and Mandala Activity on Stress and Stress-Coping Levels of Infertile Women Who Had an Embryo Transfer: A Randomized Clinical Trial.","authors":"Banu Şişli, Kerime Derya Beydağ, Aysu Yıldız Karaahmet","doi":"10.1007/s43032-025-01891-x","DOIUrl":"10.1007/s43032-025-01891-x","url":null,"abstract":"<p><p>This study aimed to evaluate the effects of mandala activity combined with two different types of music on the stress and stress-coping levels of infertile women who recently underwent an embryo transfer. The research was conducted as a single-blind randomized controlled trial between July 1, 2021, and July 31, 2022, with a total of 120 infertile women at an infertility clinic in Turkey. Data were collected using the Descriptive Information Form, the COMPI Fertility Problem Stress Scales (COMPI-FPSS), and the COMPI Coping Strategy Scales (COMPI-CSS). Participants in the two intervention groups performed a mandala activity immediately after embryo transfer, accompanied by either meditation music or music of their choice, until one day before the Beta Human Chorionic Gonadotropin (BetaHcg) test. Stress and coping levels were assessed pre- and post-intervention. Statistical analyses were conducted using SPSS. Results showed that infertility-related stress levels significantly decreased and stress-coping abilities significantly improved among women in the intervention groups compared to the control group (p < 0.05). The group performing mandala activity with meditation music exhibited the most pronounced improvements. This study concludes that mandala activity, especially when combined with meditation music, has positive effects on stress and stress-coping among infertile women undergoing embryo transfer.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3005-3012"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799994","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}
引用次数: 0
Kuntai Capsules Improve Premature Ovarian Failure by Regulating AMPK-Mediated Autophagy. 坤泰胶囊通过调节ampk介导的自噬改善卵巢早衰。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-11 DOI: 10.1007/s43032-025-01949-w
Xiaomin Ye, Miao Chen, Jiajing Zhong, Haofan Chen, Xinmiao Lin
{"title":"Kuntai Capsules Improve Premature Ovarian Failure by Regulating AMPK-Mediated Autophagy.","authors":"Xiaomin Ye, Miao Chen, Jiajing Zhong, Haofan Chen, Xinmiao Lin","doi":"10.1007/s43032-025-01949-w","DOIUrl":"10.1007/s43032-025-01949-w","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian failure (POF) is a gynecological endocrine disorder with current treatments having limitations. Kuntai capsule (KTC), a traditional Chinese medicine formulation, is thought to be beneficial for POF, but its mechanism is unclear. Network pharmacology can help explore drug mechanisms.</p><p><strong>Methods: </strong>A POF rat model was established using cyclophosphamide (CTX). Rats received low-dose KTC (0.6 g/kg/d), high-dose KTC (1.8 g/kg/d), or dehydroepiandrosterone (DHEA, positive control). Ovarian function was evaluated via histopathology, hormone assays (ELISA), apoptosis (TUNEL/flow cytometry), autophagy markers (Western blot), and network pharmacology.</p><p><strong>Results: </strong>KTC treatment (especially high-dose) ameliorated POF in CTX-treated rats, as shown by increased ovarian weight, restored estrus cycle, and improved follicle development. The serum estradiol (E2), anti-mullerian hormone (AMH), and superoxide dismutase (SOD) levels increased, whereas the follicle-stimulating hormone (FSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels decreased following KTC treatment. KTC also alleviated ovarian cell apoptosis and autophagy, with higher-dose KTC being more effective. Network pharmacology predicted AMPK/mTOR pathway involvement. Western blot confirmed KTC activated the AMPK/mTOR signaling, downregulated autophagy markers (LC3B-II/I, Beclin1), and upregulated P62. Autophagy inhibition (via 3-MA) mirrored KTC effects, while mTOR blockade (rapamycin) reversed them.</p><p><strong>Conclusions: </strong>KTC ameliorates POF by inhibiting excessive ovarian autophagy through AMPK/mTOR pathway activation, providing a mechanistic basis for its clinical use.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2970-2984"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822411","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}
引用次数: 0
The Functional Role of Cumulus Cells and Their Influence on Oocyte Quality: A Systematic Review. 积云细胞的功能作用及其对卵母细胞质量的影响:系统综述。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 10.1007/s43032-025-01940-5
Matthew C H Rohn, Jocelyn M Simeone, Steven Doctorman, Peixi Ge, Ana Hernandez, Samarjit Das, Marcus Spann, Mark Dow, James Segars, Bhuchitra Singh
{"title":"The Functional Role of Cumulus Cells and Their Influence on Oocyte Quality: A Systematic Review.","authors":"Matthew C H Rohn, Jocelyn M Simeone, Steven Doctorman, Peixi Ge, Ana Hernandez, Samarjit Das, Marcus Spann, Mark Dow, James Segars, Bhuchitra Singh","doi":"10.1007/s43032-025-01940-5","DOIUrl":"10.1007/s43032-025-01940-5","url":null,"abstract":"<p><p>A systematic review was conducted pertaining to the biologic processes of cumulus cells and measures of oocyte quality. The initial search yielded 18,549 articles, and after screening, 65 studies were included in this review. Extracted data were synthesized descriptively. Articles were categorized based on the biologic feature of cumulus cells addressed: genetic expression, biochemical activity, and morphologic characteristics. Manuscripts addressing cumulus cell function in association with gynecologic conditions and their impact on oocyte quality were also reviewed. Findings from six studies showed an association between increased expression of pathways related to extracellular matrix development (HAS2, VCAN) and improved oocyte quality. Six manuscripts reported improved oocyte quality related to genes involved in cumulus cell expansion (GREM1, PTGS2) and 6 articles noted patterns in expression of regulators of apoptotic pathways (BCL2, BIRC5, MDM2, PGAM5). Twelve studies examined biochemical features of cumulus cells, including cumulus mitochondrial membrane resistance, respirometric index, and acetyl-CoA levels, which have been associated with oocyte development. Morphologic assessment of cumulus cells was evaluated by 5 studies, demonstrating a relationship between mitochondrial dimensions, telomere length, and cumulus density/dispersion with oocyte quality. Twenty-two articles assessed cumulus cell function and its relationship with oocyte quality in diseases such as polycystic ovarian syndrome (PCOS) and endometriosis conditions, and increased maternal age (with or without decreased ovarian reserve). This comprehensive systematic review has integrated findings from studies investigating the relationship between cumulus cells and oocyte quality, identifying patterns in gene expression, biochemical features and morphologic assessments that may offer meaningful insight into this relationship.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2877-2902"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789827","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}
引用次数: 0
Association of Early-to-Mid-Luteal Serum Estradiol Levels with the Outcomes of Hormone Replacement Therapy-Frozen Embryo Transfer: A Systematic Review and Meta-Analysis. 早中期黄体血清雌二醇水平与激素替代疗法-冷冻胚胎移植结果的关联:系统回顾和荟萃分析。
IF 2.5 3区 医学
Reproductive Sciences Pub Date : 2025-09-01 Epub Date: 2025-08-13 DOI: 10.1007/s43032-025-01952-1
Azadeh Tarafdari, Fatemeh Keikha, Sepideh Ahmadi, Alireza Hadizadeh, Amirali Barkhordarioon, Mohammadamin Parsaei
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