Behzad Haj Mohammad Hassani, Niloofar Ghasemi, Kianoosh Malekzadeh
{"title":"A novel homozygous growth differentiation factor 9 variant associated with premature ovarian insufficiency: A case report.","authors":"Behzad Haj Mohammad Hassani, Niloofar Ghasemi, Kianoosh Malekzadeh","doi":"10.18502/ijrm.v23i12.20718","DOIUrl":"https://doi.org/10.18502/ijrm.v23i12.20718","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a condition marked by reduced ovarian function. The variants in several genes have been identified in association with POI. Growth differentiation factor 9 (<i>GDF9</i>) is one of these genes, which encodes a secreted protein with an essential role in follicular development.</p><p><strong>Case presentation: </strong>Our study investigates the cause of early secondary amenorrhea in 2 affected sisters with POI from a consanguineous Iranian family. Exome sequencing identified a novel homozygous <i>GDF9</i> variant (c.275T <math><mo>></mo></math> C; p.Leu92Pro) in the probands. Based on family segregation analysis, the variant was detected in a heterozygous state in the parents of the affected sisters and their grandmother. Notably, neither the mother nor the grandmother showed symptoms of the disease. Bioinformatics analysis and protein structural alteration due to the substitution of leucine with proline also supported the deleterious potential impact of this variant.</p><p><strong>Conclusion: </strong>In summary, our findings highlight the role of <i>GDF9</i> biallelic variants in the etiology of POI and suggest a more cautious interpretation of heterozygous variants in the context of disease.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 12","pages":"1043-1050"},"PeriodicalIF":1.8,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olesya Efremova, Irina Ponomarenko, Mikhail Churnosov, Olga Efremova
{"title":"Association of polymorphic loci of the matrix metalloproteinase genes with the development of fetal growth retardation: A case-control study.","authors":"Olesya Efremova, Irina Ponomarenko, Mikhail Churnosov, Olga Efremova","doi":"10.18502/ijrm.v23i12.20711","DOIUrl":"https://doi.org/10.18502/ijrm.v23i12.20711","url":null,"abstract":"<p><strong>Background: </strong>Matrix metalloproteinases (MMPs) play a crucial role in successful pregnancy as molecular regulatory factors of the developing organism. Additional studies focusing on MMPs activity and function in fetal growth retardation (FGR) may help in the search for diagnostic markers of this pregnancy complication.</p><p><strong>Objective: </strong>To study the association of <i>MMPs</i> gene polymorphisms with the development of FGR.</p><p><strong>Materials and methods: </strong>This case-control study included 122 pregnant women with FGR and 243 pregnant women with normal birth weight. We studied polymorphic loci of metalloproteinase genes: rs1799750 of <i>MMP-1</i>, rs243865 of <i>MMP-2</i>, rs3025058 of <i>MMP-3</i>, rs11568819 of <i>MMP-7</i>, rs17577 of <i>MMP-9</i>. The polymorphism study was performed by TaqMan probe detection using real-time precipitation reaction. The logistic regression method was used to analyze the association of polymorphisms with FGR.</p><p><strong>Results: </strong>The T allelic variant rs243865 of the <i>MMP-2</i> gene was found to be associated with the development of FGR under allelic (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.08-2.24, p<sub>perm</sub> = 0.016), additive (OR = 1.53, 95% CI: 1.07-2.18, p<sub>perm</sub> = 0.015) and dominant (OR = 1.61, 95% CI: 1.03-2.50, p<sub>perm</sub> = 0.027) models. The FGR-causative locus rs243865 of <i>MMP-2</i> is located in the enhancer region in the amnion and placenta tissues, affects epigenetic modifications in FGR-significant cell/organ cultures both in the embryo/fetus in the maternal body and in the mother's body, changes deoxyribonucleic acid binding affinity to the myogenic factor transcription, transcriptional activity of <i>RP11-212I21.2</i> gene in arteries.</p><p><strong>Conclusion: </strong>The T allele rs243865 of the <i>MMP-2</i> gene was found to be a risk factor for the development of FGR.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 12","pages":"985-994"},"PeriodicalIF":1.8,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of frozen embryo transfer outcomes in hormonal vs. mild stimulation protocols in polycystic ovary syndrome women: A randomized controlled trial.","authors":"Kobra Hamdi, Sahar Khakpour, Aliyeh Ghasemzadeh Darjani, Laya Farzadi, Behrouz Niknafs, Nazli Navali, Parvin Hakimi, Roghayeh Anvari Aliabad, Hamed Hajipour","doi":"10.18502/ijrm.v23i12.20712","DOIUrl":"https://doi.org/10.18502/ijrm.v23i12.20712","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility. In women undergoing frozen embryo transfer, the method of endometrial preparation (hormone replacement therapy [HRT] or mild ovarian stimulation [MOS]) can affect pregnancy outcomes. Letrozole-based MOS protocols may improve endometrial receptivity and reduce miscarriage rates by upregulating key implantation markers leukemia inhibitory factor<i>,</i> dickkopf-related protein 1<i>,</i> leukemia inhibitory factor receptor<i>,</i> fibroblast growth factor 22<i>,</i> integrin alpha V beta 3.</p><p><strong>Objective: </strong>This study aimed to compare the frozen embryo transfer outcomes in 2 endometrial preparation methods: HRT and MOS in infertile women with PCOS.</p><p><strong>Materials and methods: </strong>This double-blind randomized trial included 100 infertile women with PCOS and frozen embryos who referred to Al-Zahra hospital, Tabriz, Iran between October 2024 and 2025. Participants were assigned to HRT or MOS for endometrial preparation. In HRT, oral estradiol followed by injectable progesterone was used; in MOS, letrozole + follicle-stimulating hormone stimulation continued until follicle <math><mo>></mo></math> 17 mm and endometrium <math><mo>≥</mo></math> 7.5 mm, then human chorionic gonadotropin was given. Cleavage-stage transfer was performed in both groups, and pregnancy outcomes (chemical, clinical, and final) were compared.</p><p><strong>Results: </strong>The number of transferred embryos (p = 0.771) and their quality (types 1 and 2) (p = 0.857) were similar between groups. The number of chemical pregnancies in the MOS group (25 cases) was non-significantly higher than in the HRT group (20 cases) (p = 0.078). However, the number of clinical pregnancies (p = 0.045) and the number of successful pregnancies (p = 0.049) were significantly higher in the MOS group compared to the HRT group.</p><p><strong>Conclusion: </strong>This study showed that MOS achieved higher clinical and successful pregnancy rates than HRT in women with PCOS.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 12","pages":"995-1006"},"PeriodicalIF":1.8,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammadhossein Fakherbaheri, Hanieh Shafienia, Seyed Mehdi Kalantar, Fateme Montazeri
{"title":"Expression of <i>TGFB1</i> and <i>ERK</i> in cumulus cells: Implications for oocyte maturation in women with polycystic ovary syndrome: A cross-sectional study.","authors":"Mohammadhossein Fakherbaheri, Hanieh Shafienia, Seyed Mehdi Kalantar, Fateme Montazeri","doi":"10.18502/ijrm.v23i12.20717","DOIUrl":"https://doi.org/10.18502/ijrm.v23i12.20717","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is an endocrine disorder that negatively influences oocyte developmental competence. In vitro maturation (IVM) is an approach to reduce complications in the treatment of PCOS-related infertility. The genes regulating oocyte maturation should be investigated to evaluate oocyte quality to enhance IVM efficiency.</p><p><strong>Objective: </strong>This study aimed to examine the relationship between transforming growth factor-β1(<i>TGFB1</i>) and extracellular signal-regulated kinase (<i>ERK</i>) expression in cumulus cells (CCs) of women with PCOS and oocyte development.</p><p><strong>Materials and methods: </strong>In this cross-sectional study, a total of 40 oocytes at the germinal vesicle (GV) and 40 oocytes at metaphase II stages were retrieved from 30 PCOS women. GV oocytes were cultured in IVM medium, and samples were divided into matured and immatured groups. Intracytoplasmic sperm injection was performed, and embryo quality was evaluated. Quantitative reverse transcriptase polymerase chain reaction was used to analyze <i>TGFB1</i> and <i>ERK</i> expression levels in CCs of each group.</p><p><strong>Results: </strong>We found that the <i>TGFB1</i> and <i>ERK</i> expression was significantly lower in CCs of GV compared to metaphase II oocytes. Similar results were observed for CCs of the immatures-group compared to the matured-group. The <i>ERK</i> expression was significantly higher in fertilized oocytes compared to unfertilized ones; however, comparison of <i>TGFB1</i> expression between these groups was not significant. The expression level of <i>TGFB1</i> and <i>ERK</i> was higher in high-quality compared to low-quality embryos.</p><p><strong>Conclusion: </strong>The observed associations between <i>TGFB1</i> and <i>ERK</i> expression and reproductive outcomes highlight their potential as biomarkers for selecting competent oocytes and predicting embryo viability.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 12","pages":"1031-1042"},"PeriodicalIF":1.8,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akbar Farhadi, Farhad Zolfagharpour, Arash Abdolmaleki, Asadollah Asadi, Azam Zabihi
{"title":"Protective effects of selenium nanoparticles against X-ray-induced testicular damage in rats: An integrated experimental and Monte Carlo simulation study.","authors":"Akbar Farhadi, Farhad Zolfagharpour, Arash Abdolmaleki, Asadollah Asadi, Azam Zabihi","doi":"10.18502/ijrm.v23i11.20546","DOIUrl":"https://doi.org/10.18502/ijrm.v23i11.20546","url":null,"abstract":"<p><strong>Background: </strong>Ionizing radiation induces oxidative damage in biological tissues, particularly in sensitive organs such as the testes. Selenium nanoparticles (SeNPs), known for their antioxidant properties, may help mitigate this damage.</p><p><strong>Objective: </strong>This study investigated the protective effects of SeNPs against X-ray-induced testicular damage in rats.</p><p><strong>Materials and methods: </strong>This integrated and Monte Carlo simulation experimental study involved 42 male Wistar rats (8-10 wk, 200-250 gr), randomly assigned to 7 groups (n = 6/each). One group served as the control, while the others were exposed to 35 kilovolts X-rays at varying doses. In half of the irradiated groups, SeNPs (5 mg/kg) were administered intraperitoneally before irradiation. Biological evaluations included weight gain, testicular weight, sperm quality, histological examination, and measurements of total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI). A Geant4-DNA simulation assessed hydroxyl radical production and G-values across different SeNP concentrations during radiation's chemical stage.</p><p><strong>Results: </strong>SeNPs treatment improved biological outcomes compared with untreated irradiated rats. Sperm count increased by 7-55% (p <math><mo><</mo></math> 0.010), motility by 2-7% (p <math><mo><</mo></math> 0.050), and abnormal sperm frequency decreased by 6-18% (p <math><mo><</mo></math> 0.010). TAC increased by 2.5-15% (p <math><mo><</mo></math> 0.050), while TOS and OSI decreased (p <math><mo><</mo></math> 0.010). Histological analysis showed preserved seminiferous tubules and reduced tissue damage. Testicular weight imbalance was reduced by 50%. Simulations showed 82-93% reduction in hydroxyl radical G-values with SeNPs.</p><p><strong>Conclusion: </strong>SeNPs significantly mitigated X-ray-induced oxidative and structural testicular damage in rats.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 11","pages":"911-926"},"PeriodicalIF":1.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the molecular nexus: Long non-coding RNAs, RNA-binding proteins, and DNA damage in ovarian ischemia-reperfusion injury: A narrative review.","authors":"Ramesh Baradaran Bagheri, Shima Mohammadian","doi":"10.18502/ijrm.v23i11.20544","DOIUrl":"https://doi.org/10.18502/ijrm.v23i11.20544","url":null,"abstract":"<p><p>Ovarian ischemia-reperfusion injury (IRI) is a pathology that entails the interruption of blood supply to the ovary and subsequent restoration of flow, causing tissue damage and dysfunction. Therefore, the identification of cisternal components, long non-coding RNAs (lncRNAs), and RNA-binding proteins (RBPs), as well as their roles in the DNA damage response (DDR), is critical in understanding the underlying molecular mechanisms and finding potential therapeutic targets. Therefore, the expression profile of lncRNA and the regulation of DDR in various cellular processes can be controlled through interactions with RBPs. As scaffolds, guides or decoys regulating RNA processes, mediating DNA repair, and other cellular responses to genotoxic stress, lncRNAs play their roles. Alterations of lncRNA-RBP interactions have been involved in multiple diseases, including ovarian IRI, which prompts their further assessment as therapeutic targets. Abnormal RBPs will lead to the disruption of RNA homeostasis, a decline in DNA repair, and the exacerbation of the IRI-mediated tissue damage in the ovaries. These pathways are involved in cell cycle regulation, DNA repair, and apoptosis regulation in ovarian IRI, and manipulation of these pathways by lncRNAs and RBPs identified here may contribute to disease progression and/or serve as potential therapeutic targets. Studying these molecular processes promises almost targeted therapeutic approaches to individualized treatment. Future studies should try to understand the differential contribution of particular lncRNAs and RBPs, as well as DDR pathways involved in ovarian IRI, to provide better prognostic estimates and ameliorate ovarian function in patients.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 11","pages":"881-896"},"PeriodicalIF":1.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fimbria torsion as a rare cause of lower abdominal pain: A case report and literature review.","authors":"Solmaz Hasani, Roya Gholizadeh, Sima Rajabi Khamesi, Mohammad Ebrahim Kalantari, Mostafa Salimi","doi":"10.18502/ijrm.v23i11.20550","DOIUrl":"https://doi.org/10.18502/ijrm.v23i11.20550","url":null,"abstract":"<p><strong>Background: </strong>Isolated fimbrial torsion is a rare gynecological emergency that can lead to severe complications if not promptly diagnosed. Its clinical presentation often mimics more common causes of abdominal pain, creating a significant diagnostic challenge.</p><p><strong>Case presentation: </strong>This case report describes a 47-yr-old woman presenting with right lower quadrant abdominal pain. The initial clinical and ultrasound findings were suggestive of acute appendicitis. However, diagnostic laparoscopy revealed isolated gangrenous torsion of the right fallopian tube fimbria.</p><p><strong>Conclusion: </strong>This case underscores the importance of including fimbrial torsion in the differential diagnosis of right lower quadrant pain in women, even when clinical signs suggest a more common etiology. A comprehensive intraoperative evaluation is crucial when initial findings do not fully explain the clinical presentation, ensuring timely intervention and prevention of long-term complications.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 11","pages":"953-960"},"PeriodicalIF":1.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahsa Shirani, Mohammad Bagherniya, Omid Sadeghi, Hatav Ghasemi Tehrani, Mohammad Hadi Eskandari, Manoj Sharma, Gholamreza Askari
{"title":"Effects of supplementation with two probiotic strains on metabolic profile, hormonal status, oxidative stress, and quality of life in women with polycystic ovary syndrome: A study protocol for a randomized clinical trial.","authors":"Mahsa Shirani, Mohammad Bagherniya, Omid Sadeghi, Hatav Ghasemi Tehrani, Mohammad Hadi Eskandari, Manoj Sharma, Gholamreza Askari","doi":"10.18502/ijrm.v23i11.20547","DOIUrl":"https://doi.org/10.18502/ijrm.v23i11.20547","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women, associated with insulin resistance, ovulatory dysfunction, hyperandrogenism, and inflammation. Current treatments often focus on symptoms rather than underlying causes, emphasizing the need for comprehensive strategies. Recently, probiotics have emerged as a safe and cost-effective nutritional option for managing metabolic issues.</p><p><strong>Objective: </strong>This study aims to evaluate the effects of <i>Lactobacillus helveticus</i> and <i>Bifidobacterium longum</i> supplementation on the cardiometabolic profile, hormonal status, oxidative stress, and quality of life in women with PCOS.</p><p><strong>Materials and methods: </strong>We will conduct a double-blind, placebo-controlled, randomized trial involving 90 women with PCOS from Shahid Beheshti hospital, Isfahan, Iran. Recruitment will begin on June 20, 2024, and is expected to be completed by June 20, 2025. Participants will be randomly assigned to receive either a daily probiotic capsule containing <i>Lactobacillus helveticus</i> and <i>Bifidobacterium longum</i> or a placebo. The study will assess the impact of these probiotic strains on cardiometabolic profile, hormonal status, oxidative stress, mental health, quality of life, sleep quality, and clinical symptoms in women with PCOS. All parameters will be evaluated before and after the intervention.</p><p><strong>Discussion: </strong>Elevated insulin levels and gut microbiota imbalances significantly contribute to the development of PCOS. Growing evidence suggests that gut dysbiosis is linked to sex hormone levels and estrous cycles. We hypothesize that probiotic supplementation in individuals with PCOS will improve hormonal, metabolic, inflammatory, and antioxidant markers compared to those receiving a placebo.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 11","pages":"927-936"},"PeriodicalIF":1.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kosar Babaei, Saman Morovat, Hossein Mozdarani, Misa Naghdipour Mirsadeghi, Seyed Reza Mirhafez, Ebrahim Mirzajani, Mohsen Aziminezhad, Ali Akbar Samadani
{"title":"Integrative RNA-seq analysis reveals immune-related hub genes <i>NR4A1</i> and <i>FOSB</i> in recurrent spontaneous abortion: A bioinformatics study.","authors":"Kosar Babaei, Saman Morovat, Hossein Mozdarani, Misa Naghdipour Mirsadeghi, Seyed Reza Mirhafez, Ebrahim Mirzajani, Mohsen Aziminezhad, Ali Akbar Samadani","doi":"10.18502/ijrm.v23i11.20545","DOIUrl":"https://doi.org/10.18502/ijrm.v23i11.20545","url":null,"abstract":"<p><strong>Background: </strong>Recurrent spontaneous abortion (RSA) impacts 1-5% of women of reproductive age, constituting a significant health issue. Despite advances in our understanding of RSA, the fundamental molecular mechanisms remain inadequately defined. Examining differentially expressed genes (DEGs) in RSA may yield essential insights into the disease's pathophysiology and enable the identification of novel ameliorative targets.</p><p><strong>Objective: </strong>This study aimed to identify key DEGs, elucidate their interaction networks, and uncover potential hub regulators across decidua and villus tissues in RSA vs. control samples.</p><p><strong>Materials and methods: </strong>In this bioinformatics study, we analyzed RNA-seq datasets GSE113790 (decidua) and GSE121950 (villus) from the gene expression omnibus database using illumina-aligned count matrices. Rigorous batch correction was performed using surrogate variable analysis, followed by differential expression analysis in DESeq2 with thresholds of |log₂FC| <math><mo>≥</mo></math> 2 and false discovery rate <math><mo><</mo></math> 0.05. A high-confidence protein-protein interaction network was constructed via STRING (confidence <math><mo>></mo></math> 0.7), and functional enrichment analysis was conducted. Hub genes were identified using the maximal clique centrality, density of maximum neighborhood component, and maximum neighborhood component algorithms in CytoHubba, and the expression of top candidates was visualized across merged datasets.</p><p><strong>Results: </strong>After correction and integration, 114 protein-coding DEGs (30 upregulated and 84 downregulated) were identified. The protein-protein interaction network (101 nodes, 116 edges) was significantly enriched over random expectation (p <math><mo><</mo></math> 1 <math><mo>×</mo></math> 10<sup>-16</sup>). Enrichment analysis highlighted immune-related processes, including neutrophil chemotaxis and cytokine-mediated signaling. Cross-algorithm analysis revealed <i>NR4A1</i> and <i>FOSB</i> as consensus hubs, both significantly downregulated in RSA (<i>NR4A1</i>: log<sub>2</sub>FC = -2.15, p_adj = 4.78 <math><mo>×</mo></math> 10<sup>-20</sup>; <i>FOSB</i>: log<sub>2</sub>FC = -2.96, p_adj = 2.46 <math><mo>×</mo></math> 10<sup>-40</sup>).</p><p><strong>Conclusion: </strong>Our integrative approach delineates immune-centric molecular dysfunction in RSA and highlights <i>NR4A1</i> and <i>FOSB</i> as central regulatory genes that may drive disease pathogenesis. These findings pave the way for experimental validation and functional studies targeting immune-trophoblast signaling to inform diagnostic and therapeutic strategies in RSA.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 11","pages":"897-910"},"PeriodicalIF":1.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nasrin Malverdi, Sheida Kazemi, Negin Tavakoli, Mohammad Reza Deemeh, Mehdi Abedinzadeh, Serajoddin Vahidi, Peyman Salehi
{"title":"A special perspective on human fertilization: The role of sperm capacitation proteins and channels: A narrative review.","authors":"Nasrin Malverdi, Sheida Kazemi, Negin Tavakoli, Mohammad Reza Deemeh, Mehdi Abedinzadeh, Serajoddin Vahidi, Peyman Salehi","doi":"10.18502/ijrm.v23i11.20543","DOIUrl":"https://doi.org/10.18502/ijrm.v23i11.20543","url":null,"abstract":"<p><p>Sperm undergo a last step of maturation known as capacitation in the female reproductive system, which prepares themselves to fertilize the ovum. Mechanisms of capacitation include changes in membrane composition, electrolyte concentration, pH levels, cellular and molecular pathways, signaling cascades, sperm protein phosphorylation, and sperm-specific channel activity. Capacitation is a strictly regulated process since it must occur at the appropriate time and place. In this study, Google Scholar, Web of Science Core Collection, PubMed/MEDLINE, and Scopus were used to search and retrieve data. The 2 main consequences of capacitation are modifications to the membrane composition and changes in sperm motility type. Decapacitation factors, which are primarily located in seminal fluid, should prevent ejaculated sperm from undergoing early capacitation. The activities of decapacitation factors diminish as seminal fluid is removed and sperm enter the female genital system, whereas the capacitation factors cause sperm to become capacitated. The proteins that either stimulate or hinder the process of capacitation have been investigated in this study, with a focus on expressing their role in human capacitation as accurately as possible. The role of suitable proteins for human assisted reproductive technology and in vitro fertilization, would likely be better understood if studies could concentrate on the human route after investigating the capacitation process in various animals.</p>","PeriodicalId":14386,"journal":{"name":"International Journal of Reproductive Biomedicine","volume":"23 11","pages":"867-880"},"PeriodicalIF":1.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}