{"title":"YTHDC1 Promoted Cell Proliferation and Decidualization by Maintaining Nuclear C/EBPβ Stability in Decidual Stromal Cells.","authors":"Weihua He, Yating Zhao, Lijun Yin, Jianhua Qian","doi":"10.1007/s43032-025-01888-6","DOIUrl":"https://doi.org/10.1007/s43032-025-01888-6","url":null,"abstract":"<p><p>m6A modification has been shown to play a role in regulating female reproductive diseases. The YT521-B homology (YTH) domain family, including the m6A readers YTHDC1 and YTHDC2, is associated with decidualization during pregnancy. This study aimed to investigate the role of YTHDC1/2-regulated m6A modification in decidualization of endometrial stromal cells (ESCs). We found that YTHDC1 and YTHDC2 were highly expressed in decidual tissues from normal pregnancies. Knockdown of YTHDC1 suppressed cell proliferation and decidualization marker expression in decidual stromal cells (DSCs), whereas overexpression of YTHDC1 enhanced these processes. Mechanistically, YTHDC1 interacted with C/EBPβ via m6A modification and targeted its 3'UTR region. Knockdown of YTHDC1 accelerated the degradation of nuclear C/EBPβ mRNA in DSCs but had minimal effect on cytoplasmic C/EBPβ. Overexpression of C/EBPβ partially rescued the shYTHDC1-induced suppression of cell proliferation and decidualization markers. These results demonstrate that YTHDC1 promotes decidualization and proliferation in DSCs by stabilizing nuclear C/EBPβ mRNA through m6A modification, suggesting a novel therapeutic target for decidualization-related reproductive disorders.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216729","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}
Sean W D Carter, Qin Wei, Winston Koh, Xiawen Liu, Kay Yi Michelle Seah, Si En Poh, Haruo Usuda, Erin L Fee, Yusaku Kumagai, Tsukasa Takahashi, Lara Monteiro, Reyna Peñailillo, Hannah R S Watson, Masatoshi Saito, Owen B Spiller, Mahesh A Choolani, Sebastián E Illanes, Matthew W Kemp
{"title":"Predictive Screening for Inflammatory Disorders of Pregnancy Using Targeted Maternal Cell-Free RNA Assays: Proof-of-Principle Data from Large Animal and Human Cohorts.","authors":"Sean W D Carter, Qin Wei, Winston Koh, Xiawen Liu, Kay Yi Michelle Seah, Si En Poh, Haruo Usuda, Erin L Fee, Yusaku Kumagai, Tsukasa Takahashi, Lara Monteiro, Reyna Peñailillo, Hannah R S Watson, Masatoshi Saito, Owen B Spiller, Mahesh A Choolani, Sebastián E Illanes, Matthew W Kemp","doi":"10.1007/s43032-025-01876-w","DOIUrl":"https://doi.org/10.1007/s43032-025-01876-w","url":null,"abstract":"<p><p>The management and prevention of key inflammatory-associated pregnancy complications such as chorioamnionitis and pre-eclampsia is hampered by a lack of early gestation risk screening tools. In a proof-of-principle study we used targeted cell-free RNA analyses of maternal plasma samples from large animal (sheep) and human pregnancy cohorts to develop a minimally invasive screening test for inflammatory markers. This study utilised a preterm sheep model of sterile and bacterial chorioamnionitis. Date-mated ewes received either intraamniotic Saline Control (n = 10) or E.Coli LPS (Sterile chorioamnionitis) with 2 days (n = 9) or 8 days exposure(n = 6). Preterm lambs were delivered at 124 ± 1d gestation. Findings were validated in a bacterial model of chorioamnionitis where ewes were exposed to 7 days of intraamniotic M.Hominis with delivery at 98 d gestion(n = 8) or 128d gestation(n = 8). Maternal blood was collected prior to intervention and at delivery in each group. Random Forest algorithm was used to analyse 8 cell-free RNA(cfRNA) targets related to inflammation in maternal plasma at baseline and delivery, identifying genes that separated animals with or without intrauterine inflammation. Plasma cfRNA data was compared to mRNA expression in placental tissue. Haematological and placental mRNA comparisons were analysed with ANOVA/Tukey HSD/Dunnett T3 tests. Maternal plasma cfRNA findings of intrauterine inflammation were then validated in human plasma samples from a cohort of patients with late onset pre-eclampsia (n = 10) or uncomplicated pregnancies (n = 10). We present data showing that targeted maternal cfRNA assays can accurately identify chorioamnionitis of sterile (AUC 1.0) and infectious (AUC 0.84) origin in a sheep model of pregnancy. Findings were then validated in human maternal plasma samples from patients with late-onset pre-eclampsia in the 1st (AUC = 0.85), 2nd (AUC = 0.90) and 3rd (AUC = 0.82) trimesters. In both sheep and human model systems, cfRNA tests offered high levels of sensitivity and specificity in the absence of overt clinical symptoms. We suggest that further development of this technology may serve as a scalable, rapidly deployed and cost-effective means for predicting major inflammatory conditions in pregnancy.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216728","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}
Nuo Heng, Haisheng Hao, Yingfan Hu, Yi Wang, Huan Wang, Wei He, Ni Zhu, Rui Wang, Xiuli Xuan, Huabin Zhu, Shanjiang Zhao, Feng Wang
{"title":"Metformin Improves Palmitate-Induced Follicular Granulosa Cell Dysfunction by Activating ULK1-Mediated Autophagy.","authors":"Nuo Heng, Haisheng Hao, Yingfan Hu, Yi Wang, Huan Wang, Wei He, Ni Zhu, Rui Wang, Xiuli Xuan, Huabin Zhu, Shanjiang Zhao, Feng Wang","doi":"10.1007/s43032-025-01894-8","DOIUrl":"https://doi.org/10.1007/s43032-025-01894-8","url":null,"abstract":"<p><p>Obesity has become a global epidemic with major implications for fertility. In particular, obesity can trigger follicular atresia by initiating the apoptosis of granulosa cells (GCs). Emerging evidence suggests that this process may be closely linked to the dysregulation of cellular autophagy. Metformin has been shown to restore autophagic flux and mitigate obesity-related cellular dysfunction in mice; however, the ability of metformin to alleviate lipid overload-induced damage in goat granulosa cells has yet to be investigated. Analyses showed that 400 μM palmitic acid (PA) significantly increased lipid accumulation and reduced cell viability (P < 0.05) in goat granulosa cells. Furthermore, PA impaired mitochondrial function, associated with a significant increase in the populations of both early and late apoptotic cells (P < 0.05). However, treatment with 5 μM metformin (MET) under PA exposure significantly enhanced the viability of GCs and reduced the expression levels of pro-apoptotic BAX (P < 0.05). Next, we evaluated the effect of MET on cellular autophagy and found that MET treatment significantly downregulated the expression levels of phosphorylated mTORC1 (Ser2448), LC3B, and P62 while upregulating the expression levels of ULK1 in PA-treated GCs (P < 0.05). Our findings indicate that metformin improved palmitate-induced granulosa cell dysfunction by activating ULK1-mediated autophagy. Our findings will advance our understanding of reproductive dysfunction in obese ruminants, and provide a theoretical foundation for improving fertility in obese mammals.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216727","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}
Jiani Sun, Mei Ji, Yiping Zhu, Orhan Bukulmez, Yeung William Shu-Biu, Jing Sun, Xiaoming Teng, Miaoxin Chen
{"title":"Identification and Validation of RPL7 and RCCD1 as Potential Biomarkers Associated with Immune Infiltration in Patients with Thin Endometrium.","authors":"Jiani Sun, Mei Ji, Yiping Zhu, Orhan Bukulmez, Yeung William Shu-Biu, Jing Sun, Xiaoming Teng, Miaoxin Chen","doi":"10.1007/s43032-025-01883-x","DOIUrl":"https://doi.org/10.1007/s43032-025-01883-x","url":null,"abstract":"<p><p>Thin endometriumQuery (TE) significantly contributes to poor embryo implantation and female infertility, yet its pathogenesis remains unclear, limiting effective treatment options. To identify potential TE-associated genes and explore underlying mechanisms for clinical therapy, we conducted RNA sequencing on 18 TE and 18 normal endometrium samples, followed by bioinformatics analysis. Total RNA was extracted from samples, reverse-transcribed into cDNA, and sequenced on the HiSeq 2500 platform, followed by differential expression analysis and functional enrichment of differentially expressed genes (DEGs). Functional enrichment and LASSO analysis identified key biomarkers, which were subsequently validated at both mRNA and protein levels. Immune infiltration patterns and correlations with immune cells were also examined. Consequently, ribosomal protein L7 (RPL7) and RCC1 domain-containing 1 (RCCD1) were identified as potential biomarkers, showing overexpression in TE and association with abnormal immune regulation. These findings suggest that RPL7 and RCCD1 may serve as specific biomarkers for TE, providing insights that could aid in developing targeted therapeutics to improve clinical outcomes.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209343","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}
Muhammed Arif Ibis, Neslihan Oytun Mencik, Burcu Öztürk, Murat Can Karaburun, Cagri Akpinar, Aykut Akıncı, Hakan Bahadır Haberal, Kaan Aydos, Onder Yaman
{"title":"The Relationship Between Sperm Midpiece Details and DNA Fragmentation in Human Sperm.","authors":"Muhammed Arif Ibis, Neslihan Oytun Mencik, Burcu Öztürk, Murat Can Karaburun, Cagri Akpinar, Aykut Akıncı, Hakan Bahadır Haberal, Kaan Aydos, Onder Yaman","doi":"10.1007/s43032-025-01887-7","DOIUrl":"https://doi.org/10.1007/s43032-025-01887-7","url":null,"abstract":"<p><p>Sperm DNA fragmentation is associated with poor sperm quality and reproductive outcomes. Free radicals are a significant cause of DNA fragmentation, with mitochondria being the primary intrinsic source. To investigate the relationship between midpiece measurements containing mitochondria and sperm DNA fragmentation, and to determine the ideal midpiece area. Demographic data, semen analysis results, and DNA fragmentation values were prospectively collected from 239 men with infertility complaints. Detailed analyses and morphometric measurements were performed on 50 spermatozoa from each patient, totaling 11,950 spermatozoa. The ideal DNA fragmentation index (DFI) cutoff value was calculated. Patients were classified into three subgroups based on midpiece length, midpiece width, and midpiece area measurements. The correlation between mid-piece measurements and DFI was investigated. The cutoff value for DFI was determined as 19.50. The odds ratio evaluating the relationship between morphology status and high DFI was 0.159 (95% CI: 0.089-0.282). It was observed that midpiece length and width have statistically significant but low correlations with DFI, whereas midpiece area shows a higher correlation. Finally, based on DFI values, the ideal midpiece area was between 2.31 and 3.13 µm<sup>2</sup>. There is a significant correlation between sperm midpiece area and DFI value, surpassing that of length and width. Future studies may yield important insights by exploring the impact of midpiece area measurements on reproductive outcomes.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209356","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}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-03-27DOI: 10.1007/s43032-025-01845-3
Gokul Sudhakaran, Sanjay Gopi, Snega Priya, Raman Pachaiappan, Ilavenil Soundharrajan, Bader O Almutairi, Jesu Arockiaraj
{"title":"Apigenin Regulates Bisphenol-A Induced Polycystic Ovarian Syndrome (PCOS) Symptoms In-Vivo Zebrafish.","authors":"Gokul Sudhakaran, Sanjay Gopi, Snega Priya, Raman Pachaiappan, Ilavenil Soundharrajan, Bader O Almutairi, Jesu Arockiaraj","doi":"10.1007/s43032-025-01845-3","DOIUrl":"10.1007/s43032-025-01845-3","url":null,"abstract":"<p><p>Bisphenol A (BPA) is an environmental pollutant known to induce oxidative stress and reproductive toxicity, symptoms that are commonly associated with Polycystic Ovary Syndrome (PCOS). This study investigates the potential protective effects of Apigenin (AGN), a bioactive flavonoid, against BPA-induced PCOS-like symptoms in adult zebrafish. The research aims to explore the therapeutic potential of natural compounds in mitigating the effects of environmental endocrine disruptors. Zebrafish were exposed to BPA at a concentration of 10 µg/L, a level known to adversely affect aquatic organisms. The non-toxicity and efficacy of AGN were assessed through a dose-response study involving concentrations of 5, 10, 15, and 20 µM. The experimental design was informed by computational molecular dynamics, including docking and simulations targeting the human androgen receptor. The study involved histological staining of ovarian tissues, biochemical assays for antioxidant enzyme activities, high-performance liquid chromatography (HPLC) for BPA accumulation, and gene expression analysis targeting PCOS-susceptible genes. AGN treatment significantly modulated antioxidant defenses in zebrafish, restoring activities of enzymes such as superoxide dismutase (SOD) and catalase (CAT), and reducing lactate dehydrogenase (LDH) levels. Histologically, AGN mitigated follicular damage and prevented excessive collagen deposition and ovarian hypertrophy, with the gonadosomatic index (GSI) approaching control levels. HPLC analysis confirmed lower BPA accumulation in tissues of AGN-treated groups. Additionally, gene expression studies showed downregulation of PCOS-related genes and TNF-α. AGN exerts a protective role against BPA-induced reproductive toxicity and offers potential as a natural intervention for both ecological and reproductive health challenges.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1912-1925"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731498","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}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-04-03DOI: 10.1007/s43032-025-01828-4
Guicheng Zhao, Jun Ma, Gan Shen, Xiaohui Jiang, Xiang Wang, Chuan Jiang, Hengzhou Bai, Yi Zheng, Kun Tian, Juntao Yue, Dingming Li, Ying Shen
{"title":"Identification of an SMC1B Mutation Associated With Necrozoospermia and Failure of Testi-ICSI : SMC1B Mutation Associated With Necrozoospermia.","authors":"Guicheng Zhao, Jun Ma, Gan Shen, Xiaohui Jiang, Xiang Wang, Chuan Jiang, Hengzhou Bai, Yi Zheng, Kun Tian, Juntao Yue, Dingming Li, Ying Shen","doi":"10.1007/s43032-025-01828-4","DOIUrl":"10.1007/s43032-025-01828-4","url":null,"abstract":"<p><p>Investigating potential etiologies is important before selecting a therapeutic approach for male infertility. However, the genetic causes of idiopathic necrozoospermia are poorly understood. In this study, a heterozygous missense variant in SMC1B (NM_148674.5: c1856G > T; p.C619F) causing severe necrozoospermia in the infertile proband was identified by Whole-exome sequencing (WES). This phenotype was distinct from the phenotypes of other vertebrates harboring this mutation. Interestingly, Papanicolaou staining, light microscopy and electron microscopy results indicated severe abnormalities in the morphology of the sperm head and an irregular sperm ultrastructure in the patient with the identified variant. Additionally, the sharply decreased protein expression of SMC1B in spermatozoa and testicular tissues ultimately resulted in an abnormal chromatin structure and high sperm DNA fragmentation (SDF) in the male patient. Regrettably, poor outcomes of Intracytoplasmic sperm injection with testicular sperm (Testi-ICSI) treatment were observed for the patient harboring the identified SMC1B mutation. In Conclusion, a missense SMC1B mutation that may mediate impaired sperm vitality was the first time reported, providing new insights into a novel genetic etiology of necrozoospermia in humans.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2050-2063"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781104","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":"Three Novel Mutations in TUBB8 Cause Female Infertility Due to Multiple Morphological Abnormalities of the Oocyte and Early Embryo.","authors":"Duan Li, Guanghui Yuan, Xiaoxiao Wang, Jiao Zhuang, Lie Wang, Yingxue Liu, Xiaowen Liu, Linfang Han, Huaiqian Dou, Bing Li, Cuifang Hao","doi":"10.1007/s43032-025-01844-4","DOIUrl":"10.1007/s43032-025-01844-4","url":null,"abstract":"<p><p>Recent years have seen a global increase in infertility, affecting up to 17.5% of the population. For successful human reproduction, the proper development process of the oocyte, fertilization, and early embryo is required. Assisted reproductive technology (ART), which is the primary treatment for infertility, uses the morphology of oocytes and zygotes as parameters to predict ART outcomes. However, factors such as large perivitelline space (PVS), centrally located granular cytoplasm (CLGC), multi-pronuclei (MPN) formation, and final early embryonic development arrest often lead to repeated failure of ART treatment. Genetic analysis has identified various pathogenic genetic factors contributing to infertility, suggesting that genetic variation plays a significant role in recurrent ART treatment failure. However, maternal genes responsible for large PVS, CLGC, and MPN formation are rarely reported. In this study involving Whole Exome Sequencing (WES) and Sanger sequencing validation, three novel heterozygous missense mutations (p.M403V, p.R306H, p.H190Y) in TUBB8 were identified as being associated with large PVS, CLGC, MPN formation, and early embryonic development arrest. These mutant sites are evolutionarily conserved in different species. Additionally, in silico and in vitro experiments demonstrate that these variants disrupt the conformation, expression, and microtubule structures of the TUBB8 protein. Therefore, these findings contribute significantly to understanding TUBB8-related large PVS, CLGC, and MPN formation in the context of ARTs. This broadens our insight into the genetic connection in human reproduction and emphasizes the importance of comprehensive genetic screening and personalized intervention strategies for PVS, CLGC, and MPN formation.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1813-1824"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995646","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}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-05-07DOI: 10.1007/s43032-025-01859-x
Alyson Dennis, Emily Weidenbaum, Jennifer K Blakemore, Jacquelyn Shaw
{"title":"Ovarian Torsion after Controlled Ovarian Hyperstimulation Cycles with a Prolonged Recovery State: A Case Series and Review of the Literature.","authors":"Alyson Dennis, Emily Weidenbaum, Jennifer K Blakemore, Jacquelyn Shaw","doi":"10.1007/s43032-025-01859-x","DOIUrl":"10.1007/s43032-025-01859-x","url":null,"abstract":"<p><p>We aim to present two rare cases of ovarian torsion immediately following controlled ovarian hyperstimulation and their prolonged recovery state at an academic fertility center. Patient 1 is a 38-year-old nulligravid woman with a history of prior right oophorectomy and patient 2 is a 37-year-old nulligravid woman with a previous left oophorectomy. The main objective of our paper is to characterize the recovery time after ovarian detorsion surgery. These case reports highlight that ovarian torsion after controlled ovarian hyperstimulation may be associated with prolonged systemic symptoms including increased abdominal pain, persistent low-grade fevers, and mild leukocytosis for several weeks following laparoscopic ovarian de-torsion. A proposed mechanism for this extended inflammatory state could be due to higher levels of luteinizing hormone surge activating Phospholipase C-Protein Kinase C pathway and vascular endothelial growth factors involved in follicular growth and luteinization.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1905-1911"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034642","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}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-05-08DOI: 10.1007/s43032-025-01870-2
Li Wang, Yihui Li, Chengting Dai, Yi Yuan, Qingxin Yuan, Jianbo Li
{"title":"Mechanisms of LncRNA FTX in Regulating Islet Function of Pregnant Mice Born With Low-Protein Diet-Induced Intrauterine Growth Retardation.","authors":"Li Wang, Yihui Li, Chengting Dai, Yi Yuan, Qingxin Yuan, Jianbo Li","doi":"10.1007/s43032-025-01870-2","DOIUrl":"10.1007/s43032-025-01870-2","url":null,"abstract":"<p><p>Glucose metabolism during pregnancy in adult females born with intrauterine growth restriction (IUGR) remains inadequately understood. This study aims to investigate how LncRNA FTX regulates islet function during pregnancy in F1 female mice born with IUGR (F1 IUGR pregnant mice). A pregnant mouse model was established using F1 female mice born with IUGR (F1 IUGR pregnant mouse model). Intraperitoneal glucose tolerance test (IPGTT), immunohistochemistry (IHC) staining, quantitative real-time PCR (qPCR) were performed in both F1 IUGR and normal mice during pregnancy and non-pregnancy periods. RNA-sequencing was conducted on islets from F1 IUGR and normal pregnant mice. Insulin-related gene expression analysis, cell proliferation, and apoptosis assessment were performed in TC6 cells following FTX knockdown or overexpression. A luciferase reporter assay was conducted to validate the molecular interactions. F1 IUGR pregnant mice exhibited a smaller increase in insulin-staining area and lower upregulation of insulin-related gene expression levels compared to normal pregnant mice. There were 1,007 differentially expressed lncRNAs between F1 IUGR and normal pregnant islets; among these, FTX was down-regulated during pregnancy, although its downregulation in F1 IUGR pregnant mice was less pronounced than in normal pregnant mice. FTX was closely related to cell proliferation activity, apoptosis, insulin-related transcription factor expression. The pten/PI3K/AKT pathway was also regulated by FTX. Luciferase reporter assay confirmed FTX acted as a competing endogenous RNA (CeRNA) to target pten by sponging miR-22-3p. LncRNA FTX regulates islet function during pregnancy in F1 mice born with IUGR via the miR-22-3p/pten axis.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1939-1952"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993531","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}