Reproductive Sciences最新文献

{"title":"Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation.","authors":"Mina Moayeri, Shiva Irani, Marefat Ghaffari Novin, Iman Salahshourifar, Mohammad Salehi","doi":"10.1007/s43032-024-01640-6","DOIUrl":"10.1007/s43032-024-01640-6","url":null,"abstract":"<p><p>The molecular mechanism responsible for sperm DNA fragmentation is not fully understood. Therefore, identifying genes related to the response to DNA damage is an important area of research. Recently, the role of long non-coding RNAs (LncRNAs), especially DNA damage-sensitive RNA1 (DDSR1) in male infertility has been highlighted. In this research, a protein-protein interaction network (PPIN) was constructed using the STRING database, and functional classification was conducted using webgestalt servers. Subsequently, a group of 40 males with a high degree of sperm DNA fragmentation (DFI ≥ 25%) was compared to a control group of 20 healthy males with a normal sperm DNA fragmentation rate (DFI < 25%). To assess gene expression, real-time polymerase chain reaction (PCR) analysis was performed on DNA samples obtained from both healthy and infertile males. Our findings revealed that infertile men with an abnormal DFI index showed significantly lower expression levels of the long noncoding RNA DDSR1, as well as the genes BRCA1, MRE11A, RAD51, and NBN, compared to the control group. Pathway analysis of the network proteins using Reactome indicated involvement in crucial cellular processes such as the cell cycle, DNA repair, meiosis, reproduction, and extension of telomeres. In conclusion, the downregulation of LncRNA and genes associated with the DNA damage response in males with an abnormal DFI suggests that these factors may contribute to the development of sperm DNA fragmentation and could potentially serve as diagnostic markers for further investigation in therapeutic interventions in the future.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627516","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":"Clinical Applications of Assisted Oocyte Activation in Couples with Various Reproductive Problems: A Systematic Review.","authors":"Shayesteh Mehdinejadiani, Nasim Goudarzi, Fatemeh Masjedi, Azam Govahi, Maryam Mirani, Kobra Mehdinejadiani, Nahid Azad","doi":"10.1007/s43032-024-01671-z","DOIUrl":"10.1007/s43032-024-01671-z","url":null,"abstract":"<p><p>ICSI may face fertilization failure, prompting the use of assisted oocyte activation (AOA) techniques. While AOA is implemented in infertility clinics, its target patients and definitive application remain uncertain. This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess reproductive outcomes in ICSI-AOA cycles compared to conventional ICSI and evaluate AOA effectiveness in various infertility disorders. A literature search encompassed PubMed, Web of Science, EMBASE, and Scopus databases until December 2023 for relevant English studies. Included studies compared ICSI-AOA with conventional ICSI in couples with prior fertilization failure, utilizing diverse AOA methods. Control groups consisted of sibling oocytes, previous cycles of the same couples, or couples undergoing conventional ICSI. Evaluated outcomes included fertilization, cleavage, embryo quality, implantation, pregnancy, and live birth rates. Article screening and data extraction were performed by two authors, with risk of bias assessed by another investigator. Out of 3088 initially identified articles, 30 studies were included, focusing on fertilization failure (n = 10), female infertility (n = 3), PLCζ defects (n = 4), poor sperm quality (n = 4), Globozoospermia (n = 4), and surgically retrieved sperm (n = 8). Most studies concluded that AOA could overcome fertilization failure, but success rates varied based on sperm-related or oocyte-related factors in ICSI-AOA cycles. Due to differences in patient inclusion criteria and sample sizes, most studies were not sufficiently similar for pooled analysis, limiting robust conclusions. There is insufficient evidence, particularly from randomized controlled trials (RCTs), to determine the efficacy or safety of ICSI-AOA as a treatment strategy. Registration number is PROSPERO, CRD42024551221.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018407","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":"Integrating Bioinformatics and Experimental Validation to Identify Mitochondrial Permeability Transition-Driven Necrosis-Related lncRNAs that can Serve as Prognostic Biomarkers and Therapeutic Targets in Endometrial Carcinoma.","authors":"Ting Zhou, Haojia Li, Qi Zhang, Shuangshuang Cheng, Qian Zhang, Yuwei Yao, Kejun Dong, Zheng Xu, Wan Shu, Jun Zhang, Hongbo Wang","doi":"10.1007/s43032-024-01693-7","DOIUrl":"https://doi.org/10.1007/s43032-024-01693-7","url":null,"abstract":"<p><p>Endometrial carcinoma (EC) is a common malignant tumor in women with high mortality and relapse rates. Mitochondrial permeability transition (MPT)-driven necrosis is a novel form of programmed cell death. The MPT-driven necrosis related lncRNAs (MRLs) involved in EC development remain unclear. We aimed to predict the outcomes of patients with EC by constructing a novel prognostic model based on MRLs and explore potential molecular functions. A risk prognostic model was developed utilizing multi-Cox regression in conjunction with the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm, which was based on MRLs. The predictive efficacy of the model was evaluated through receiver operating characteristic (ROC) curve analysis, as well as nomogram and concordance index (C-index) assessments. Patients were categorized into high- and low-risk groups based on their median risk scores. Notably, the high-risk group exhibited significantly poorer overall survival (OS) outcomes. Gene ontology (GO) and Gene set enrichment analysis (GSEA) demonstrated that Hedgehog and cell cycle pathways were enriched in the high-risk group. Tumor Immune Dysfunction and Exclusion (TIDE) displayed that patients in the high-risk group showed a high likelihood of immune evasion and less effective immunotherapy. A significant disparity in immune function was also observed between two groups. Based on the nine-MRLs, drug sensitivity analysis identified several anticancer drugs with potential efficacy in prognosis. Meanwhile, the results demonstrated that OGFRP1 plays a carcinogenic role by affecting mitochondrial membrane permeability in EC. Therefore, the risk model constructed by nine MRLs could be used to predict the clinical outcomes and therapeutic responses in patients with EC effectively.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352773","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-Analytical and Meta-Regression Evaluation of Subclinical Hyperthyroidism's Effect on Male Reproductive Health: Hormonal and Seminal Perspectives.","authors":"Seyed Sobhan Bahreiny, Akram Ahangarpour, Elham Rajaei, Mohammad Sharif Sharifani, Mojtaba Aghaei","doi":"10.1007/s43032-024-01676-8","DOIUrl":"10.1007/s43032-024-01676-8","url":null,"abstract":"<p><p>Subclinical hyperthyroidism (SCH) is a subtle thyroid dysfunction marked by decreased serum thyroid-stimulating hormone (TSH) levels while maintaining a normal thyroid hormone profile. Despite its mild nature, SCH can significantly impact various physiological functions, including male reproductive health. However, the effects of SCH on reproductive hormones and semen quality are less understood compared to overt thyroid disorders. This study employed extensive search methods across various databases from January 2000 to February 2024 to explore the relationship between SCH and Hormonal and Seminal Perspectives. Effect sizes, estimated using the standardized mean difference (SMD) and pooled with a Random-effect model, provided significant insights from 748 participants. Included studies adhered to the following criteria: Patients (male individuals with SCH), Intervention (assessment of reproductive hormones and semen quality), Comparison (SCH patients versus healthy controls), and Outcome (changes in reproductive factors). Significant alterations in reproductive hormones were observed in SCH patients, including reduced LH levels (SMD =  - 0.20; p = 0.007), elevated FSH levels (SMD = 0.25; p = 0.002), and stable testosterone levels (SMD =  - 0.05; p = 0.50). Regarding thyroid profile, SCH was associated with increased FT3 (SMD = 0.15; p < 0.001) and FT4 (SMD = 0.08; p = 0.002) levels, along with decreased TSH levels (SMD =  - 2.00; p < 0.001). Adverse effects on semen quality were also observed. These findings underscore the need to incorporate thyroid health assessments in the evaluation of male infertility, recognizing the impact of minor thyroid hormone deviations on reproductive outcomes.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018408","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":"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Morbidity following Trial of Labor after Cesarean in Women Experiencing Antepartum Fetal Death.","authors":"Ela Kadish, Tzuria Peled, Hen Y Sela, Ari Weiss, Shaked Shmaya, Sorina Grisaru-Granovsky, Misgav Rottenstreich","doi":"10.1007/s43032-024-01645-1","DOIUrl":"10.1007/s43032-024-01645-1","url":null,"abstract":"<p><p>This study aims to investigate whether trial of labor after cesarean delivery (TOLAC) in women with antepartum fetal death, is associated with an elevated risk of maternal morbidity. A retrospective multicenter. TOLAC of singleton pregnancies following a single low-segment incision were included. Maternal adverse outcomes were compared between women with antepartum fetal death and women with a viable fetus. Controls were matched with cases in a 1:4 ratio based on their previous vaginal births and induction of labor rates. Univariate analysis was followed by multiple logistic regression modeling. During the study period, 181 women experienced antepartum fetal death and were matched with 724 women with viable fetuses. Univariate analysis revealed that women with antepartum fetal death had significantly lower rates of TOLAC failure (4.4% vs. 25.1%, p < 0.01), but similar rates of composite adverse maternal outcomes (6.1% vs. 8.0%, p = 0.38) and uterine rupture (0.6% vs. 0.3%, p = 0.56). Multivariable analyses controlling for confounders showed that an antepartum fetal death vs. live birth isn't associated with the composite adverse maternal outcomes (aOR 0.96, 95% CI 0.21-4.44, p = 0.95). TOLAC in women with antepartum fetal death is not associated with an increased risk of adverse maternal outcomes while showing high rates of successful vaginal birth after cesarean (VBAC).</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591166","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":"The Association Between Maternal ABO Blood Group and the Occurrence of Spontaneous Preterm Birth: A Retrospective Population-Based Cohort Study.","authors":"Eyal Rom, Manal Massalha, Offer Erez, Raed Salim","doi":"10.1007/s43032-024-01705-6","DOIUrl":"https://doi.org/10.1007/s43032-024-01705-6","url":null,"abstract":"<p><p>There is limited and inconsistent evidence that imply a relationship between ABO blood types and rate of preterm birth (PTB). We aim to examine the association between maternal ABO blood group and PTB rate. A retrospective-study conducted at a university teaching institution on data collected between 2013 and 2019. Women who delivered a viable neonate at ≥ 24 weeks without major malformations were included. Indicated PTBs were excluded. PTB and early PTB were defined as deliveries that occurred < 37 and < 34 weeks respectively. PTB was further divided into 3 subgroups according to etiology: membranes rupture, intact membranes, and placental abruption regardless of membranes' status. The primary outcome was spontaneous PTB rate. Of 19,301 women included, PTB and early PTB rates were 7.3% (1,418/19,301) and 2.3% (440/19,301) respectively. Rates of PTB in blood groups A, B, O, and AB, were 7.3%, 6.9%, 7.5%, and 7.5% respectively (p = 0.68). There was no significant difference according to etiology. Rates of early PTB were also comparable (p = 0.63). After adjustment for demographic and obstetric variables, blood type was associated with increased placental abruption rate among women who had early PTB (p = 0.038). Placental abruption rate was significantly higher in group A (22.5%) compared to group B (14.1%), (adjusted p = 0.04) and group O (14.0%), (adjusted p = 0.01). The rate in group AB was 17.1%, (adjusted p = 0.85). In conclusion, no association was found between a particular blood group and PTB rate. Women with group A, admitted in early PTB, had an increased risk that the underlying etiology was placental abruption.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352778","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":"Perspective in the Mechanisms for Repairing Sperm DNA Damage.","authors":"Nihong Li, Hong Wang, Siying Zou, Xujun Yu, Junjun Li","doi":"10.1007/s43032-024-01714-5","DOIUrl":"https://doi.org/10.1007/s43032-024-01714-5","url":null,"abstract":"<p><p>DNA damage in spermatozoa is a major cause of male infertility. It is also associated with adverse reproductive outcomes (including reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage). The damage to sperm DNA occurs during the production and maturation of spermatozoa, as well as during their transit through the male reproductive tract. DNA damage repair typically occurs during spermatogenesis, oocytes after fertilization, and early embryonic development stages. The known mechanisms of sperm DNA repair mainly include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). The most severe type of sperm DNA damage is double-strand break, and it will be repaired by DSBR, including homologous recombination (HR), classical non-homologous end joining (cNHEJ), alternative end joining (aEJ), and single-strand annealing (SSA). However, the precise mechanisms of DNA repair in spermatozoa remain incompletely understood. DNA repair-associated proteins are of great value in the repair of sperm DNA. Several repair-related proteins have been identified as playing critical roles in condensing chromatin, regulating transcription, repairing DNA damage, and regulating the cell cycle. It is noteworthy that XRCC4-like factor (XLF) and paralog of XRCC4 and XLF (PAXX) -mediated dimerization promote the processing of populated ends for cNHEJ repair, which suggests that XLF and PAXX have potential value in the mechanism of sperm DNA repair. This review summarizes the classic and potential repair mechanisms of sperm DNA damage, aiming to provide a perspective for further research on DNA damage repair mechanisms.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352774","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":"Factors Associated to the Presence of Isthmocele Diagnosed by Pelvic Ultrasound, Magnetic Resonance Imaging or Diagnostic Hysteroscopy: A Cross-Sectional Study.","authors":"João Paulo Leonardo-Pinto, Luiz Gustavo Oliveira Brito, Renata Teles Piva Belluomini, Cristina Laguna Benetti-Pinto, Daniela Angerame Yela","doi":"10.1007/s43032-024-01711-8","DOIUrl":"https://doi.org/10.1007/s43032-024-01711-8","url":null,"abstract":"<p><p>We aimed to analyze the prevalence of isthmocele and factors associated with its onset within a cohort of women with previous history of cesarean section. A cross-sectional study with 90 women assessed from 2020 to 2022. Isthmocele was a composite variable diagnosed by transvaginal ultrasound (TVUS), magnetic resonance imaging (MRI) and/or diagnostic hysteroscopy (DxHys) and were asked about clinical symptoms, sociodemographic and obstetrical history and quality of life by the WHO-QOL questionnaire. Univariate and multivariate analysis (odds ratio (OR) plus 95% confidence intervals-CI) were performed to seek factors associated with the presence of isthmocele (5% significance level).The prevalence of isthmocele after combining MRI, TVUS and DxHys was 63.3% (n = 57). Women with isthmocele presented a higher body mass index (BMI) measured during delivery (32.70 ± 6.07 vs. 28.28 ± 9.86 kg/m²;p < 0.05) than women without isthmocele. Other sociodemographic variables, obstetrical history and WHO-QOL subdomains did not differ between groups. Within women with isthmocele, the residual myometrial mantle had an average of 4.97 ± 1.57 cm. Uterine volume was higher in the isthmocele group (103.95 vs. 81.34 cm³; p = 0.08), but with no statistical difference. Multivariate analysis (logistic regression) has reported that the factors associated with isthmocele were: higher BMI during delivery (aOR = 1.26[1.07-1.49];p < 0.05); longer interpartum interval (aOR = 1.22[1.03-1.46];p = 0.02) and presence of more than two cesarean sections (aOR = 2.16[1.16-4.01];p = 0.02). We concluded that a high prevalence of isthmocele was found. Women with previous cesarean section, with higher BMI during delivery and longer interdelivery interval were risk factors for the presence of isthmocele.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352772","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":"Combination Therapy with Vitamin D and Metformin: A Potential Approach to Mitigate Testicular Dysfunction in Type 2 Diabetes Mellitus.","authors":"Adeyemi Fatai Odetayo, Halimat Amin Abdulrahim, Adedotun Muiz Yusuf, Williams Oshetename Aromokhame, Ademola Muritala Olaitan, Mirabel Chisom Ugoji, Moses Agbomhere Hamed, Luqman Aribidesi Olayaki","doi":"10.1007/s43032-024-01708-3","DOIUrl":"https://doi.org/10.1007/s43032-024-01708-3","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a multifactorial disease that cannot be linked to a single pathway, causing the observed heterogeneity among T2DM patients. Despite this level of heterogeneity, T2DM is majorly managed by metformin (MET) monotherapy. However, recent findings have associated long-term metformin intake with progressive oxidative pancreatic β cell damage as the disease progresses. Hence, a significant number of patients treated with MET need an alternate therapy. Hence, identifying drug combinations that can effectively alleviate different diabetes complications would serve as a more promising therapy that can translate into active use. Hence, this study was designed to explore the possible synergistic effect of vitamin D and metformin on T2DM-induced testicular dysfunction. Thirty healthy male Wistar rats (weight: 120-150 g and age: 10 ± 2 weeks) were randomly divided into control, diabetes untreated (HFD+STZ), diabetes + vitamin D (1000 IU/kg), diabetes + metformin (180 mg/kg), and diabetes + vitamin D + metformin. All treatments lasted for 28 days and animals were sacrificed using IP injection of ketamine and xylaxine (40 and 4 mg/kg respectively). Vitamin D improved the ameliorative effect of metformin on T2DM-induced hyperglycemia and lipid dysmetabolism, accompanied by a significant decrease in testicular lactate dehydrogenase and lactate. Also, vitamin D + metformin significantly increased serum luteinizing hormone, follicle-stimulating hormone, testosterone, and testicular 5α reductase activities. Furthermore, vitamin D improved the anti-inflammatory and antioxidant effects of metformin by significantly decreasing T2DM-induced increase in testicular interleukin 1beta, interleukin 6, TNF-α, nitric oxide, and NF-κB and increasing T2DM-induced decrease in interleukin 10, glutathione, superoxide dismutase, catalase, GPx, and Nrf2. Vitamin D enhanced the ameliorative effect of metformin on T2DM-induced testicular dysfunction.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352770","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}