Reproductive biology最新文献

{"title":"Testis-specific gene C3ORF22/BC048671 is dispensable for spermiogenesis and male fertility","authors":"Shiyue Du ,&nbsp;Yongfu Liu ,&nbsp;Le Wang ,&nbsp;Liuliu Shi ,&nbsp;Xiaoying Zhao ,&nbsp;Zhongcheng Yang ,&nbsp;Wei Yuan ,&nbsp;Xiaoying Deng ,&nbsp;Jiahua Liu ,&nbsp;Shenglei Feng ,&nbsp;Rui Chen","doi":"10.1016/j.repbio.2025.101089","DOIUrl":"10.1016/j.repbio.2025.101089","url":null,"abstract":"<div><div>Testicular tissue displays the most complex transcriptome across all tissues, with over 2000 genes exhibiting testis-enriched expression patterns. However, the functional ambiguity of such genes limits our understanding of spermatogenesis and male fertility. Here, we reanalyzed testicular gene expression profiles from patients with impaired spermatogenesis and identified that reduced expression of the testis-specific gene <em>C3ORF22</em> was correlated with spermatogenic defects in humans. We showed that the murine ortholog <em>BC048671</em> was predominant expressed in round spermatids, and its protein is present in spermatozoa. <em>BC048671</em> knockout (KO) mice exhibited normal fertility, sperm morphology, and sperm motility. Intriguingly, RNA-Seq analysis revealed that <em>BC048671</em> was the most markedly dysregulated gene in KO testes. Although proteomic analysis reveals the down-regulated ADAM family members (e.g., ADAM28 and ADAM2) in <em>BC048671</em>-null sperm, expression of the key downstream effector ADAM3 remained unaffected. These findings indicate that <em>BC048671</em>/<em>C3ORF22</em> exhibits functional redundancy in spermatozoa. Although <em>C3ORF22</em> is dispensable for male fertility, we consider it essential to report such negative results to guide researchers to prioritize efforts toward genes critical for human fertility.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101089"},"PeriodicalIF":2.5,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Casimiroa edulis extract modulates testosterone levels, testicular enzymes and spermatogenesis disorders in streptozotocin-induced diabetic male rats","authors":"Aya A. Mahmoud,&nbsp;Amel Ramadan Omar,&nbsp;Heba Ali Abd El-Rahman","doi":"10.1016/j.repbio.2025.101088","DOIUrl":"10.1016/j.repbio.2025.101088","url":null,"abstract":"<div><div>Diabetes mellitus is a serious health issue that adversely affects male reproductive function and contributes to the rise in male infertility. This study examined the effectiveness of <em>Casimiroa edulis</em> leaf extract in improving reproductive impairment in diabetic male rats. Forty male rats were divided into control, <em>Casimiroa edulis</em> extract-treated, diabetic, and diabetic + <em>Casimiroa edulis</em> groups. Diabetic rats showed a notable reduction in sperm quality, a considerable rise in serum cholesterol levels, accompanied by a decrease in both androstenedione and testosterone levels. Histological examination of testicular tissue revealed degeneration of the seminiferous tubules, depletion of germinal cells, and lack of Leydig cells. They also exhibited a notable reduction in the activity of testicular enzymes, specifically 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, along with a rise in the level of dehydroepiandrosterone. <em>Casimiroa edulis</em> treatment substantially reduced cholesterol levels, enhanced the activity of testicular enzymes, and restored testicle structure. Consequently, testosterone levels were elevated, and sperm quality was improved. To conclude, <em>Casimiroa edulis</em> may mitigate the negative effects of diabetes mellitus on the reproductive parameters of male rats and enhance fertility.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101088"},"PeriodicalIF":2.5,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA mediated downregulation of HSD17B1 impairs estrone-to-estradiol conversion in polycystic ovarian syndrome","authors":"Prajna Bhandary ,&nbsp;Prasanna Kumar Shetty ,&nbsp;Praveenkumar Shetty ,&nbsp;Lakshmi Manjeera ,&nbsp;Prakash Patil","doi":"10.1016/j.repbio.2025.101085","DOIUrl":"10.1016/j.repbio.2025.101085","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a complicated disorder with genetic and epigenetic factors as the potential contributors of disease progression. The major findings of PCOS involves an imbalanced estrogen and androgen. The gene <em>HSD17B1</em> is known to be involved in the synthesis of these steroids. Because miRNAs, which are short non-coding RNAs that regulate genes, are promising therapeutic possibilities for disease regulation, this study focused on the effect of miRNAs that target the <em>HSD17B1</em> gene in PCOS. TargetScan database was used to identify the target miRNAs of <em>HSD171B1</em>. In-silico approaches were employed for prediction of expression levels of <em>HSD17B1</em>, miR-4430 and miR-200b-5p in PCOS and for the functional annotations of miRNAs. Validated the relative expression of <em>HSD17B1,</em> miR-4430, miR-200b-5p and HSD17B1 protein levels in the serum PCOS and control (n = 40/each group) using RT-qPCR and ELISA. Estrone (E1), and androstenedione (A4), were significantly increased and estradiol (E2) was significantly decreased in PCOS. The relative expression shows, overexpression of miR-4430, miR-200b-5p and reduced expression of <em>HSD17B1</em> gene as well as lower HSD17B1 protein level in PCOS. The <em>in-silico</em> functional annotation indicated that these miRNAs are involved pathways related to PCOS pathogenesis such as steroid synthesis and cell proliferation. Additionally, the diagnostic effectiveness by ROC analysis shows AUC for <em>HSD17B1</em>, miR-4430 and miR-200b-5p is 0.874, 0.869, and 0.943 respectively, reflecting a good diagnostic biomarker for PCOS. In conclusion, study indicates that overexpressed miR-4430 and miR-200b-5p probably limits the synthesis of estrone to estradiol via <em>HSD17B1</em> in PCOS.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101085"},"PeriodicalIF":2.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring critical hub genes and potential drug candidates for PCOS: A systems biology approach","authors":"Ali Ahmadizad Firouzjaei ,&nbsp;Ali Mahmoudi ,&nbsp;Natalia Elizova ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.repbio.2025.101078","DOIUrl":"10.1016/j.repbio.2025.101078","url":null,"abstract":"<div><div>Polycystic ovarian syndrome (PCOS) is widely recognized as the most common endocrine disorder in women of reproductive age. We aimed to identify PCOS-related genes by searching the Gene Expression Omnibus (GEO) database, and subsequently used the DESeq2 tool in the R program to identify differentially expressed genes. We constructed a protein-protein interaction (PPI) network for the upregulated genes in PCOS and applied the MCODE algorithm to identify significant clustering groups and hub candidates. Additionally, we performed an enrichment analysis using the ClueGO plugin to explore the biological processes and pathways associated with the upregulated genes. We successfully obtained the dataset GSE155489 from the GEO database and identified 198 elevated genes. The biological functions associated with the upregulated genes were predominantly related to steroid binding, chemokine activity, and pyridoxal phosphate binding. Results from the molecular docking study indicated that three drugs, namely Ponatinib, Dihydroergotamine, and Paliperidone, exhibited the lowest binding affinity energy and displayed the highest interaction with the most critical hub genes identified through the PPI network analysis (WNT5A, SERPINE1, and CXCR4). In summary, our findings highlight several crucial genes involved in PCOS and suggest that Ponatinib, Dihydroergotamine, and Paliperidone may have a significant impact on these genes. However, it is important to note that further research and well-designed clinical trials are necessary, as there is limited evidence from small-population clinical trials regarding the repurposing of drugs for PCOS. Advancements in PCOS knowledge will aid in the development of innovative medications for the disorder.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101078"},"PeriodicalIF":2.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of nicotinamide mononucleotide against soybean isoflavone induced damage in mouse testis","authors":"Kaixuan Wang ,&nbsp;Haiwei He ,&nbsp;Yadan Jin ,&nbsp;Fangdi Zhang ,&nbsp;Ruixue Ma ,&nbsp;Fei Wang ,&nbsp;Baohua Li ,&nbsp;Guoliang Zhang","doi":"10.1016/j.repbio.2025.101080","DOIUrl":"10.1016/j.repbio.2025.101080","url":null,"abstract":"<div><div>Soybean isoflavone (SI) was one type of phytoestrogen that competitively interacts with estrogen in the body, potentially interfering with endocrine balance, spermatogenesis, and the normal function of testicular cells. Nicotinamide mononucleotide (NMN), an important bioactive substance, enhances organ and tissue function through mechanisms such as reducing oxidative stress. However, limited information exists regarding the ability of NMN to improve phytoestrogen-induced damage to testis development in mice. The study investigated the protective effect of NMN on testicular damage in mice caused by SI. The results of this study revealed SI-treated mice exhibited a significant reduction in body weight, testicular index, and reproduction-related factors, as well as a marked increase in apoptosis. RNA sequencing (RNA-seq) results demonstrated that exposure to SI led to the enrichment of differentially expressed genes (DEGs) primarily in cellular autophagy and proliferation pathways within mouse testicular tissues. Administration of SI at doses of 200 mg/kg and 400 mg/kg downregulated the <em>Rb1cc1</em> gene in the longevity-regulating pathway and the <em>Vav2</em> gene in the cAMP signaling pathway in mouse testes. In contrast, treatment with 100 mg/kg NMN significantly alleviated the adverse effects induced by SI. In summary, NMN exhibited significant therapeutic potential in alleviating SI-induced testicular damage.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101080"},"PeriodicalIF":2.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tannic acid protection against oxidative and inflammatory effects of monosodium glutamate on testis: Molecular and biochemical approach","authors":"Sümeyye Çınar Özkan,&nbsp;Emine Toraman","doi":"10.1016/j.repbio.2025.101077","DOIUrl":"10.1016/j.repbio.2025.101077","url":null,"abstract":"<div><div>In this study, the toxic effects of monosodium glutamate (MSG), a widely used food additive, on rat testicular tissue were evaluated and the potential protective role of tannic acid (TA), a natural polyphenolic compound, against this toxicity was investigated. For this purpose, 24 rats were divided into four groups (n=6). They were administered 2 g/kg monosodium glutamate (MSG) for 21 days. Subsequently, they were treated with 50 mg/kg tannic acid (TA). At the end of this period, testicular tissues were collected for molecular and biochemical analyses. Antioxidant enzyme activities (SOD, CAT, GPx, GST, GR), oxidative stress markers (GSH, MDA), inflammatory markers (TNF-α, iNOS, COX-2) and DNA damage indicator 8-OHdG (8-hydroxy-2′-deoxyguanosine) levels were analyzed in the experimental groups. In addition, expression levels of antioxidant defense (<em>Sod, Cat, Gpx, Gst, Gr</em>), inflammation (<em>Tnf-α, Il-6, Nf-κB, Cox-2, Inos, Foxo1, Foxo3</em>) and reproductive function-related genes (<em>Dazl, Ddx4, Amh</em>) were evaluated by qPCR. In the MSG group, a decrease in GSH level and a significant increase in MDA, TNF-α, iNOS and 8-OHdG levels were found (P&lt;0.01). While a decrease was observed in SOD, CAT, GST and GR enzyme activities (P&lt;0.01), no significant change was found in GPx activity. At the gene level, MSG administration suppressed the expression of genes related to antioxidant and germ cell functions and increased the expression of <em>Tnf-α, lL-6, Cox-2</em> and <em>Foxo3</em> (P&lt;0.001). On the other hand, TA, both alone and in combination with MSG, demonstrated ameliorative effects on inflammation and oxidative stress, although not on all parameters. The data suggest that MSG induces oxidative stress, inflammation, DNA damage, and impaired germ cell function in testicular tissue. It was concluded that TA treatment suppresses these harmful effects, supports cellular defenses, and may help preserve testicular function.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101077"},"PeriodicalIF":2.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating testicular dysfunction: Metformin’s role in combating valproic acid-induced damage in rats","authors":"Alzahraa Ahmed Elhemiely ,&nbsp;Wessam H. Elesawy ,&nbsp;Hayat A. Abd El Aal ,&nbsp;Ali S. Abdelhameed ,&nbsp;Giorgio Ivan Russo ,&nbsp;Eman S.G. Hassan","doi":"10.1016/j.repbio.2025.101082","DOIUrl":"10.1016/j.repbio.2025.101082","url":null,"abstract":"<div><div>The male reproductive system is significantly affected by valproic acid (VPA), an anti-epileptic medication recognized for its detrimental effects on testicular function. This study evaluates the protective role of metformin, a hypoglycemic agent, against VPA-induced testicular dysfunction in rats. Male Sprague-Dawley rats were randomly assigned into four groups (6 rats per group): a control group, a metformin group (50 mg/kg/day), a VPA group (500 mg/kg/day), and a co-treatment group receiving both VPA and metformin. The treatments were administered for 42 days. Parameters evaluated included sperm characteristics, hormone levels, oxidative stress markers, inflammatory mediators, and apoptotic indicators. VPA exposure led to a pronounced decline in sperm motility and count, coupled with increased sperm abnormalities and decreased testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels. Additionally, VPA induced oxidative stress, evidenced by elevated malondialdehyde (MDA) and diminished reduced glutathione, alongside the suppression of Nrf2, HO-1, and NQO1 expressions. The inflammatory response was marked by heightened expression of IL-1β, TNF-α, and TGF-β proteins. VPA also upregulated Caspase-3 and downregulated PCNA, signalling increased apoptosis. Metformin co-administration effectively counteracted these alterations, restoring oxidative balance, mitigating inflammation, and reducing apoptosis to near-normal levels. Metformin significantly alleviates VPA-induced testicular damage by enhancing antioxidant defences via the Nrf2/HO-1/NQO-1 pathway and suppressing inflammatory and apoptotic cascades (TGF-β/TNF-α/IL-1β and Caspase-3/PCNA).</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101082"},"PeriodicalIF":2.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inducible differentiation of buffalo (Bubalus bubalis) embryonic stem cells towards male and female germ cell-like lineages under ex vivo BMP4-mediated stimulation","authors":"Syed Mohmad Shah ,&nbsp;Manmohan Singh Chauhan","doi":"10.1016/j.repbio.2025.101084","DOIUrl":"10.1016/j.repbio.2025.101084","url":null,"abstract":"<div><div>Bone Morphogenetic Proteins have been reported to play important roles in developmental biology across the species. The present study investigates the role of BMP4 in inducing germ lineage development. For this purpose, buffalo ES cells were subjected to <em>in vitro</em> differentiation under suspension as well as adherent cultures, at different BMP4 doses and time periods. ES cell colonies were differentiated as EBs as well as adherent monolayers under different BMP4 concentrations (20, 50 and 100 ngml⁻¹) for different time intervals (4, 8 and 14 days). The differentiated cultures were subjected to transcriptional profiling for germ lineage associated genes. qPCR data analysis revealed that BMP4 at a concentration of 50–100 ngml⁻¹ and for a period of 14 days led to maximum induction of such germ lineage associated genes like <em>DAZL</em>, <em>VASA</em>, <em>PLZF</em> (PGC-specific); <em>SYCP</em>3, <em>MLH</em>1, <em>TNP</em>1/2 and <em>PRM</em>2 (Meiotic genes); <em>BOULE</em> and <em>TEKT</em>1 (Spermatocyte markers); and <em>GDF</em>9, <em>ZP</em>2 and 3 (Oocyte markers). Immunocytochemical analysis of the differentiated cultures revealed positive expression of PGC-markers (c-KIT, DAZL and VASA), Meiotic-markers (SYCP3, MLH1 and PROTAMINE1), Spermatocyte-markers (ACROSIN and HAPRIN) and Oocyte-markers (GDF9 and ZP4), marking thereby the differentiation towards germ lineage cells. Oocyte-like structures (OLS) obtained in monolayer differentiated cultures harbored a big nucleus covered with a ZP4 coat, so typical of an oocyte. These OLS, in extended cultures, showed embryonic development and progressed through different embryonic-like structures. Global DNA methylation analysis of the optimally differentiated cultures showed significantly (p &lt; 0.05) decreased levels of 5-methyl-2-deoxycytidine, a mimic of the methylation erasure process typical of gametogenesis. Expression of PGC markers, methylation erasure, and meiotic markers together with expression of spermatocyte and oocyte markers is suggestive of post-meiotic progression into spermatogenesis and oogenesis, respectively- thus reflecting onset of <em>in vitro</em> gametogenesis.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101084"},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ganoderma lucidum mitigates oxidative stress and apoptosis in chlorpyrifos‑induced testicular toxicity in male rats","authors":"Afshin Talebinasab ,&nbsp;Farrokh Modarresi ,&nbsp;Ebrahim Salimi-Sabour ,&nbsp;Mojtaba Sepandi ,&nbsp;Maryam Ghorbani ,&nbsp;Gholam Reza Kaka ,&nbsp;Javad Raouf Sarshoori","doi":"10.1016/j.repbio.2025.101086","DOIUrl":"10.1016/j.repbio.2025.101086","url":null,"abstract":"<div><div>Chlorpyrifos (CPS) is an organophosphate pesticide known to induce oxidative stress, apoptosis, and histopathological damage in male reproductive tissues. <em>Ganoderma lucidum</em> (GDL), a medicinal fungus rich in bioactive polysaccharides and triterpenoids, has demonstrated potent antioxidant and antiapoptotic properties in various models. This study aimed to evaluate the protective effects of GDL extract against CPS-induced testicular toxicity in male rats by assessing histological integrity, oxidative stress markers, apoptosis signaling, and hormonal balance. Twenty-four adult male Wistar rats were randomly divided into four groups (n = 6): Cont, CPS (20 mg/kg), GDL (150 mg/kg), and Treat. Treatments were administered orally once daily for 30 days. At the end of the study, the testes were harvested for morphometric and Cosentino histopathological scoring, immunohistochemistry for BAX, BCL2, and Ki67, RTqPCR quantification, biochemical assays of antioxidant enzymes and serum testosterone, LH, and FSH measurements. CPS treatment significantly elevated histopathological damage scores, and disrupted regular cell arrangement. IHC revealed increased BAX and decreased BCL2 and Ki67 expression, corroborated by the upregulation of <em>Bax</em> and <em>Caspase3</em> transcripts and downregulation of <em>Bcl2</em>. Antioxidant enzymes were suppressed and MDA was elevated in the CPS group. Hormonal assays showed decreased testosterone and LH. Co-administration of GDL partially restored histological architecture, normalized Voronoi patterns, attenuated apoptotic marker alterations, enhanced antioxidant defenses, reduced lipid peroxidation, and recovered hormone levels toward control values. GDL extract confers significant protection against CPS-induced testicular injury by mitigating oxidative stress, modulating apoptotic pathways, and preserving endocrine function, highlighting its therapeutic potential against pesticide-related reproductive toxicity.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101086"},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin-loaded Chitosan nanoparticles alleviate insulin resistance in the polycystic ovarian syndrome rat model through modulation of PI3K/AKT/ GLUT4 in ovarian tissue","authors":"Samah Magdy Issa ,&nbsp;Eman H. Thabet ,&nbsp;Abeer.E. Dief ,&nbsp;Walaa Omar ,&nbsp;Samar R. Saleh ,&nbsp;Marwa M. Essawy ,&nbsp;Eman El Eter","doi":"10.1016/j.repbio.2025.101081","DOIUrl":"10.1016/j.repbio.2025.101081","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a common disorder in females characterized by insulin resistance (IR), hyperandrogenemia and anovulation. The etiology of PCOS is unknown. However, disrupted phosphatidylinositol 3-kinase (PI3K) and protein kinase B/AKT signaling pathway may be a possible cause of IR in PCOS. Metformin can activate AKT via PI3K and improve IR. However, metformin alone has shown conflicting results. Chitosan nanoparticles (CSNPs) are natural nano-carriers with anti-diabetic effects. Therefore, we aimed to elucidate the therapeutic potential of metformin-loaded CSNPs (CSNPs-Met) in a letrozole-induced PCOS rat model. The study comprised five groups of rats: control, PCOS, PCOS plus metformin, PCOS plus CSNPs, and PCOS plus CSNPs-Met. Letrozole was found to successfully induce PCOS, as evidenced by elevated serum testosterone levels, homeostasis model assessment-insulin resistance (HOMA-IR), an increased number of cystic follicles, fewer corpora lutea and a disturbed estrus cycle. The pAKT and GLUT4 protein levels were significantly lower in ovarian and muscular tissues than in control group (P &lt; 0.001), suggesting impaired insulin signaling and glucose transport that may contribute to both the metabolic and reproductive disturbances. CSNP-Met showed a significant decrease in testosterone, HOMA-IR, cystic follicles with an increase in the number of corpora lutea, as well as the levels of pAKT and GLUT4 in ovarian and muscular tissues (P &lt; 0.001). In addition, the estrus cycle was restored to normal levels. Hence, CSNPs-Met showed superior efficacy in ameliorating PCOS-associated parameters relative to metformin alone. In addition, these results support future translational studies to explore the clinical applicability of CSNPs in PCOS management.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101081"},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}