Reproductive biomedicine online最新文献

{"title":"Patients with mutations in DNAH2, DNAH6 and DNAH10 causing multiple morphological abnormalities of human sperm flagella achieve good ICSI outcomes","authors":"Xueqi Li ,&nbsp;Haibing Yu ,&nbsp;Xiangrong Tang ,&nbsp;Shunhua Long ,&nbsp;Tingwenyi Hu ,&nbsp;Jing Ma ,&nbsp;Guicen Liu ,&nbsp;Xiaolin Liu ,&nbsp;Wei Han ,&nbsp;Weiwei Liu ,&nbsp;Haiyuan Liao ,&nbsp;Guoning Huang ,&nbsp;Yingxiong Wang ,&nbsp;Tingting Lin","doi":"10.1016/j.rbmo.2025.104949","DOIUrl":"10.1016/j.rbmo.2025.104949","url":null,"abstract":"<div><h3>Research questions</h3><div>What additional genetic mutations in <em>DNAH2, DNAH6</em> and <em>DNAH10</em> are linked to multiple morphological abnormalities of sperm flagella (MMAF), and what are the assisted reproductive outcomes in couples affected by these mutations?</div></div><div><h3>Design</h3><div>A cohort of 75 infertile males with MMAF underwent whole-exome sequencing and Sanger sequencing to identify pathogenic mutations. Papanicolaou staining and electron microscopy were employed to evaluate sperm morphology and ultrastructure. Immunofluorescence was performed to characterize ultrastructural abnormalities at the molecular level, and explore the underlying molecular mechanisms by which mutations in <em>DNAH2, DNAH6</em> and <em>DNAH10</em> genes lead to MMAF.</div></div><div><h3>Results</h3><div>Ten mutations were identified in six unrelated infertile males and were predicted to be pathogenic by bioinformatic tools. Papanicolaou staining and scanning electron microscopy showed that all the male patients harbouring mutations in the <em>DNAH2, DNAH6</em> and <em>DNAH10</em> loci displayed severe sperm morphological defects, predominantly characterized by the absence and reduced length of sperm flagella. Transmission electron microscopy (TEM) revealed substantial loss of inner dynein arms and mitochondrial damage, and immunofluorescence data further supported the findings of TEM and indicated a possible interaction between DNAH2 and DNAH10. Moreover, five out of six affected couples achieved a live birth via intracytoplasmic sperm injection (ICSI).</div></div><div><h3>Conclusions</h3><div>The data suggest that patients with <em>DNAH2, DNAH6</em> and <em>DNAH10</em> mutations causing severe asthenoteratozoospermia can achieve favourable outcomes through ICSI. These findings broaden the spectrum of <em>DNAH2, DNAH6</em> and <em>DNAH10</em> mutations, and provide valuable insights for future genetic counselling of infertile males with MMAF.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 2","pages":"Article 104949"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IVF embryo and gestational sac size variation at different gestations according to embryo transfer date","authors":"Sughashini Murugesu ,&nbsp;Amy Shearer ,&nbsp;Kristofer Linton-Reid ,&nbsp;Danai Balfoussia ,&nbsp;Monica Mittal ,&nbsp;Catriona Stalder ,&nbsp;Eric O. Aboagye ,&nbsp;Srdjan Saso ,&nbsp;Sotirios Saravelos ,&nbsp;Tom Bourne","doi":"10.1016/j.rbmo.2025.104956","DOIUrl":"10.1016/j.rbmo.2025.104956","url":null,"abstract":"<div><h3>Research question</h3><div>Do embryo and gestational sac sizes vary at known gestational age points according to the date of embryo transfer in IVF cycles, and can embryo transfer date contribute to definitive miscarriage diagnosis?</div></div><div><h3>Design</h3><div>A retrospective cohort study, within a London tertiary IVF unit between 2019 and 2021. In this unit, patients undergoing fresh or frozen IVF cycles had their embryos transferred at day 3–6 of development. Patients with a confirmed intrauterine pregnancy at first scan (&lt;9 weeks gestation) were included. The data collected included embryo transfer date, embryo age at transfer and early pregnancy ultrasound measurements, including crown–rump length (CRL) and mean sac diameter (MSD). The end point was viability at the 11–14-week dating scan.</div></div><div><h3>Results</h3><div>A total of 1161 IVF embryo transfers were included in the study; 892 (76.8%) remained viable on ultrasound at 11–14 weeks and 269 (23.2%) were non-viable. In the viable cohort at the end of the first trimester, a range of embryo and gestational sac sizes were seen at specific gestational ages. The widest variation of embryo CRL was at 49 days (1–17 mm) and at 42 days for empty MSD (7–18 mm). A gestational sac with no fetal pole, at or beyond 47 days’ gestation by embryo transfer date (<em>n</em> = 157), had a 100% positive predictive value for miscarriage, with a 100% specificity (CI 90.1 to 100.0).</div></div><div><h3>Conclusions</h3><div>The CRL and MSD size vary significantly between pregnancies of the same gestational age by embryo transfer date. At 47 days’ gestation and beyond, an empty gestational sac resulted in miscarriage. If confirmed in larger studies, this may permit women to be given an earlier definitive diagnosis of miscarriage.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 3","pages":"Article 104956"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal melatonin concentration to improve functional characteristics and fertilization capacity in thawed cryopreserved human spermatozoa","authors":"Larissa Namie Chiba ,&nbsp;Juliana Risso Pariz ,&nbsp;Joël R. Drevet ,&nbsp;Ana Flávia Quiarato Lozano ,&nbsp;Jorge Hallak","doi":"10.1016/j.rbmo.2025.104950","DOIUrl":"10.1016/j.rbmo.2025.104950","url":null,"abstract":"<div><h3>Research question</h3><div>What is the optimal concentration of melatonin for improving sperm quality and function post-thawing during the cryopreservation process?</div></div><div><h3>Design</h3><div>This study aimed to evaluate the seminal parameters, and the functional effects of melatonin supplementation at three different concentrations (0.01, 2 and 3 mM) on human spermatozoa post-thawing after cryopreservation by the slow freezing method. Semen analysis was performed before and after cryopreservation to determine cryosurvival rates post-thawing. Additional assessed sperm parameters included DNA fragmentation, mitochondrial status, lipoperoxidation, reactive oxygen species content, total antioxidant capacity, glutathione content, plasma membrane integrity, sperm acrosome integrity, and hyaluronan binding ability.</div></div><div><h3>Results</h3><div>Notably, 2 mM melatonin significantly improved acrosome integrity (from 34.33 ± 12.55% to 36.33 ± 17.95%; <em>P</em> = 0.040), hyaluronic acid binding (from 87.1 ± 2.44% to 92.8 ± 1.97%; <em>P</em> = 0.002), and total antioxidant capacity (from 0.0117 ± 5.33 nmol/µl to 0.0130 ± 6.19 nmol/µl; <em>P</em> = 0.040), while higher concentrations did not yield additional benefits compared with the control group.</div></div><div><h3>Conclusions</h3><div>Based on functional tests, 2 mM melatonin is the optimal concentration to supplement sperm samples before cryopreservation by the slow freezing method to improve sperm quality and function characteristics.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 3","pages":"Article 104950"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression","authors":"Iveta Yotova ,&nbsp;Katharina Proestling ,&nbsp;Florian M. Pauler ,&nbsp;Lisa Rainer ,&nbsp;Leonie Kaup ,&nbsp;Jana Heine ,&nbsp;Lejla Sandrieser ,&nbsp;René Wenzl ,&nbsp;Quanah J. Hudson","doi":"10.1016/j.rbmo.2025.104942","DOIUrl":"10.1016/j.rbmo.2025.104942","url":null,"abstract":"<div><h3>Research question</h3><div>Is <em>LINC01638</em> involved in regulation of epithelial-to-mesenchymal transition (EMT) in endometriosis?</div></div><div><h3>Design</h3><div>A prospective patient cohort study was combined with functional experiments in the 12Z endometriosis epithelial cell line to investigate the role of <em>LINC01638</em> in endometriosis. Eutopic endometrial samples were collected by curettage, and ectopic endometrial lesion samples were collected by laparoscopic surgery from 24 control patients and 41 patients with endometriosis. The phenotype of 12Z cells was assessed following <em>LINC01638</em> knockdown using siRNA, performing proliferation, adhesion, migration and invasion assays, as well as assessing apoptosis and cell cycle changes with flow cytometry assays. In order to assess the relationship between <em>LINC01638</em> and histone deacetylase class 1 enzyme (HDAC1), <em>LINC01638</em> knockdown was combined with HDAC inhibition with the specific HDAC inhibitor romidepsin.</div></div><div><h3>Results</h3><div><em>LINC01638</em> was up-regulated in the epithelial layer of endometriotic lesions, and <em>LINC01638</em> knockdown in 12Z cells led to reduced proliferation, adhesion, migration and invasion. The reduction in proliferation was associated with increased p21 and p27 expression, and G1 phase arrest. Further analysis of <em>LINC01638</em> control and knockdown cells revealed that a number of transcription factors associated with EMT are down-regulated in knockdown cells, along with the cytoskeleton regulatory gene <em>RHOB</em>, while HDAC1 was up-regulated. Chromatin immunoprecipitation analysis and HDAC1 inhibitory treatment combined with <em>LINC01638</em> knockdown indicated that <em>LINC01638</em> regulates <em>RHOB</em> expression via HDAC1-mediated promoter deacetylation. RHOB is up-regulated in the epithelial layer of endometriotic lesions compared with eutopic endometrium, supporting a role in the disease.</div></div><div><h3>Conclusions</h3><div><em>LINC01638</em> is an epigenetic regulator of the pathogenesis of endometriosis, promoting proliferation and EMT of endometriotic lesions.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 3","pages":"Article 104942"},"PeriodicalIF":3.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From body mass index to body composition in female infertility","authors":"Ezgi Darıcı ,&nbsp;Francisca Pais ,&nbsp;Lynn Leemans ,&nbsp;Laurence Strypstein ,&nbsp;Herman Tournaye ,&nbsp;Michel De Vos ,&nbsp;Elisabeth De Waele ,&nbsp;Christophe Blockeel","doi":"10.1016/j.rbmo.2025.104941","DOIUrl":"10.1016/j.rbmo.2025.104941","url":null,"abstract":"<div><div>Obesity – a global epidemic that the World Obesity Federation expects will affect one in five women by 2030 – is an important factor influencing reproductive health. Its impact extends beyond subfertility, encompassing menstrual irregularities, oligo-anovulation, early pregnancy loss, and complications during pregnancy and delivery. The interplay between excess adiposity, metabolic health and reproductive function is complex, as adipose tissue secretes several adipokines, such as adiponectin and leptin, targeting reproductive and endocrine tissues. However, investigating the role of obesity on fertility and choosing how to define and quantify obesity remains a major challenge. Traditional reliance on body mass index (BMI) may oversimplify this relationship, as individuals with similar BMI can exhibit differing levels of metabolic health and fertility outcomes depending on their body composition and fat distribution. This narrative review examines the relationship between body composition, adiposity and abnormal body weight in reproductive health outcomes, with a focus on fertility and treatment success in women. The analysis evaluates the impact of body composition on fertility treatments, particularly IVF, and discusses implications for clinical practice. By synthesizing current evidence, this review aims to inform future research and guide the development of personalized clinical strategies in reproductive medicine.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 3","pages":"Article 104941"},"PeriodicalIF":3.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Day 3 embryo quality impact on euploidy rate and pregnancy outcomes: a retrospective study of 12,669 PGT-A embryos","authors":"Xu Han ,&nbsp;Wen Zhang ,&nbsp;Yi Xiang ,&nbsp;Mengting Teng ,&nbsp;Mei Sun ,&nbsp;Peihao Liu","doi":"10.1016/j.rbmo.2025.104924","DOIUrl":"10.1016/j.rbmo.2025.104924","url":null,"abstract":"<div><h3>Research question</h3><div>Is there any difference in euploidy rate and outcomes between blastocysts derived from poor- and good-quality day 3 embryos?</div></div><div><h3>Design</h3><div>This retrospective cohort study included a total of 1492 preimplantation genetic testing for aneuploidies cycles with 12,669 day 3 embryos. These were divided into good- and poor-quality groups based on the morphological quality on day 3. The study compared the blastocyst formation rates between the two groups, as well as the euploidy rate of the blastocysts and the pregnancy outcomes after transferring the euploid blastocysts.</div></div><div><h3>Results</h3><div>The blastocyst formation rate was significantly higher in the day 3 good-quality group compared with the day 3 poor-quality group (53.6% versus 19.3%, <em>P</em> &lt; 0.001). There was no significant difference in the blastocyst euploidy rate between the two groups (43.8% versus 42.6%, <em>P</em> = 0.150). When euploid blastocysts were transferred, a significant difference was observed in the biochemical pregnancy rate between the two groups (68.8% versus 76.3%, <em>P</em> = 0.028), while no significant differences were found in the clinical pregnancy rate (61.4% versus 66.7%, <em>P</em> = 0.143), miscarriage rate (15.1% versus 18.4%, <em>P</em> = 0.317), ectopic pregnancy rate (0.5% versus 0.0%, <em>P</em> = 0.587) and live birth rate (51.4% versus 53.5%, <em>P</em> = 0.562).</div></div><div><h3>Conclusions</h3><div>Day 3 embryo quality significantly influenced blastocyst formation rate, but did not affect either blastocyst euploidy or pregnancy outcomes. This indicates that once embryos can develop into transferrable blastocysts, their quality may be considered to be of a comparable level regardless of the morphology of their cleavage stage.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 2","pages":"Article 104924"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A sentiment analysis of YouTube videos from donor-conceived people, utilizing artificial intelligence (ChatGPT)","authors":"Sharon Galperin ,&nbsp;Lauren Wiener ,&nbsp;Olivia Chafitz ,&nbsp;Sara Bittman ,&nbsp;Antonia F. Oladipo","doi":"10.1016/j.rbmo.2025.104907","DOIUrl":"10.1016/j.rbmo.2025.104907","url":null,"abstract":"<div><h3>Research question</h3><div>What is the tone of donor-conceived people (DCP) towards their donor-conceived status in YouTube videos assessed for sentiment analysis via ChatGPT, a natural language-processing tool?</div></div><div><h3>Design</h3><div>A cross-sectional analysis of YouTube videos using the keyword ‘donor conceived’ was performed by two independent reviewers. Videos were selected for inclusion if they described DCPs’ opinions, stories or emotions about their life experiences. Reviewers categorized the sentiments of the videos as neutral, positive, negative or mixed. The auto-generated English-language YouTube transcript for each video was then inputted into ChatGPT (GPT-4o model) using the following prompt: ‘Given this text, what is the sentiment conveyed? Is it positive or negative? Text: {transcript}’. Sentiment results generated via ChatGPT were categorized as neutral, positive, negative or mixed. Chi-squared goodness-of-fit and independence tests were performed to assess the observed proportions of sentiments compared with the expected distribution.</div></div><div><h3>Results</h3><div>Fifty YouTube videos were identified. The median video length was 6.91 min and the median number of views was 2217.5. Via ChatGPT, 44% of videos were determined to have a positive sentiment, 28% were negative, 24% were mixed and 4% were neutral, with a significant difference in the observed distribution of sentiments from expected (<em>Χ</em>² [3, <em>n</em> = 50] = 16.240, <em>P</em> = 0.001). When compared with two human reviewers, ChatGPT sentiment results had 90% concordance with at least one reviewer.</div></div><div><h3>Conclusion</h3><div>ChatGPT shows a strong performance in analysing YouTube video transcript sentiments when compared with human reviewers. The sentiments of DCP towards their donor-conceived status in YouTube videos have a positive leaning when analysed by ChatGPT.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 2","pages":"Article 104907"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Universal post-warming dilution of vitrified embryos: impact of different vitrification/warming kits, warming volume and rapid dilution/rehydration steps on survival and clinical outcomes","authors":"Lodovico Parmegiani ,&nbsp;Gabor Vajta ,&nbsp;Colleen Lynch ,&nbsp;Alessandra Arnone ,&nbsp;Silvia Bernardi ,&nbsp;Antonio Manuel Maccarini ,&nbsp;Sara Lanzilotti ,&nbsp;Azzurra Rastellini ,&nbsp;Enzo Troilo ,&nbsp;Elena Nardi ,&nbsp;Walter Ciampaglia","doi":"10.1016/j.rbmo.2025.104923","DOIUrl":"10.1016/j.rbmo.2025.104923","url":null,"abstract":"<div><h3>Research question</h3><div>Is the universal warming protocol efficient to warm vitrified human blastocysts when combining different brands of vitrification and warming kits, when reducing warming droplet volume, and when using a single rehydration step (universal single-step warming)?</div></div><div><h3>Design</h3><div>Two retrospective longitudinal cohort studies (CS1 and CS2) were undertaken, including a total of 3071 vitrified/warmed blastocysts. In CS1, embryos were vitrified/warmed with various combinations of different kits, and the universal warming protocol was performed with fixed volumes of warming solutions: 4 ml of 1M non-permeating solute (NPS) at 37°C; and 300 µl of 0.5M NPS and 300 µl of washing solution at room temperature. In CS2, embryos were vitrified/warmed with various combinations of different kits. Warming was performed using single-step elution in 4 ml of 1M NPS at 37°C, or a small droplet (500 μl) of 1M NPS solution at 37°C, and subsequent washings at 37°C. The primary outcome measure was cryosurvival rate, and the secondary outcome measures were clinical pregnancy rate and embryo implantation rate (also live birth rate and neonatal outcome for CS1 alone).</div></div><div><h3>Results</h3><div>The cryosurvival rate varied between 99.5% and 100%, and was comparable between the study groups. Clinical pregnancy and embryo implantation rates were comparable between all groups in both studies. Live birth rate and neonatal outcome were comparable between the groups in CS1.</div></div><div><h3>Conclusions</h3><div>It is possible to combine various kits for vitrification/warming, and universal warming can be efficient when reducing the volume of the first warming solution. This study demonstrated, for the first time, that it is possible to perform universal single-step warming with any brand of warming kit.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 3","pages":"Article 104923"},"PeriodicalIF":3.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative effects of Gly[14]-humanin on cyclophosphamide-induced premature ovarian insufficiency and underlying mechanisms","authors":"Jin Huang ,&nbsp;Yumeng Liu ,&nbsp;Liping Zou ,&nbsp;Changhong Zhu ,&nbsp;Wei Xia","doi":"10.1016/j.rbmo.2025.104901","DOIUrl":"10.1016/j.rbmo.2025.104901","url":null,"abstract":"<div><h3>Research question</h3><div>Can Gly[14]-humanin (HNG) improve cyclophosphamide-induced premature ovarian insufficiency (POI)?</div></div><div><h3>Design</h3><div>A POI model was induced in female rats by intraperitoneal injection of cyclophosphamide, followed by treatment with an intraperitoneal injection of HNG. Ovarian weight, ovarian index, regularity of the oestrous cycle, numbers of various types of follicle, hormone concentrations, and expression of the proliferation marker Ki67 were assessed in rats, and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining was performed. The human ovarian granulosa cell line COV434 was exposed to the cyclophosphamide metabolite 4-hydroperoxy cyclophosphamide (4-HC), followed by HNG treatment. Cell viability and single-cell clone formation after HNG treatment were also evaluated. Reactive oxygen species (ROS), mitochondrial ROS (mtROS), 5-ethynyl-2′-deoxyuridine (EdU) and Ki67 expression, and Western blot analysis were performed to evaluate the expression of apoptosis-related proteins (Bcl-2 and Bax) and phosphorylated STAT3 protein.</div></div><div><h3>Results</h3><div><strong>:</strong> HNG mitigated cyclophosphamide-induced ovarian damage significantly in rats by restoring the disrupted oestrous cycle and sex hormone concentrations while reducing follicular depletion (<em>P</em> &lt; 0.05) and apoptosis (<em>P</em> &lt; 0.001). HNG treatment enhanced cell viability (<em>P</em> &lt; 0.01) without causing abnormal cell proliferation. Furthermore, HNG ameliorated the 4-HC-induced damage in COV434 cells by enhancing cell viability, increasing the expression of proliferation markers (EdU and Ki67) and reducing ROS and mtROS concentrations (<em>P</em> &lt; 0.05). HNG also decreased the 4-HC-induced elevation in Bax expression, and increased the expression of Bcl-2 and phosphorylated STAT3 (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div><strong>:</strong> The mitochondrial-derived peptide analogue HNG confers protection against cyclophosphamide-induced POI in rats by reducing oxidative stress and apoptosis. These findings suggest the potential of HNG as a therapeutic agent for preventing cyclophosphamide-induced POI in women.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 3","pages":"Article 104901"},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TKTL1: a new candidate gene in non-obstructive azoospermia","authors":"Agnieszka Malcher ,&nbsp;Mikołaj Smolibowski ,&nbsp;Tomasz Stokowy ,&nbsp;Hermann Bauer ,&nbsp;Alicja Patyk ,&nbsp;Piotr Jedrzejczak ,&nbsp;Jagoda Kostyk ,&nbsp;Zuzanna Graczyk ,&nbsp;Rim Ibrahim ,&nbsp;Katarzyna Bednarek-Rajewska ,&nbsp;Anna Berger ,&nbsp;Alexander N Yatsenko ,&nbsp;Maciej Kurpisz","doi":"10.1016/j.rbmo.2025.104895","DOIUrl":"10.1016/j.rbmo.2025.104895","url":null,"abstract":"<div><h3>Research question</h3><div>What role does <em>TKTL1</em> gene serve in human spermatogenesis and does its mutation trigger non-obstructive azoospermia (NOA)?</div></div><div><h3>Design</h3><div>The genetic background of NOA remains poorly explored. Recent studies using next generation sequencing techniques, however, have uncovered some NOA causative genes, including the <em>TKTL1</em> gene. The aim of this study was to define the function of the <em>TKTL1</em> gene in human spermatogenesis by inducing its overexpression in human testicular primary (hTP) cells, and verifying these results in male gonad tissue samples collected from patients with NOA determining the genes cluster regulated by <em>TKTL1</em>.</div></div><div><h3>Results</h3><div>Successful overexpression of the <em>TKTL1</em> gene was achieved in hTP cells; the <em>TKTL1</em> gene expression was significantly higher in genetically modified cells compared with both controls applied. RNA-sequencing was used to select 20 genes in which expression significantly differed in the modified hTP cells overexpressing <em>TKTL1</em> gene compared with controls. Male gonad tissue samples collected from patients with NOA harbouring a mutation in the <em>TKTL1</em> gene showed a significant downregulation in <em>HERC5, CSF3, HES1</em> and <em>HSPA1B</em> genes, compared with patients with azoospermia without mutation in the <em>TKTL1</em> gene (negative control) as well as control samples with normal spermatogenesis. This was in accordance with results obtained with hTP cells, as the overexpression of the <em>TKTL1</em> gene correlated with an increased expression level of the mentioned genes compared with controls.</div></div><div><h3>Conclusions</h3><div>The <em>TKTL1</em> gene is likely involved in the regulation of gametogenesis affecting the proliferation and differentiation of germ cells at the early stage of spermatogenesis.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 3","pages":"Article 104895"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}