National Engineering Research Center of Human Stem Cells

Infertility affects about 15% of couples globally, with genetic factors contributing significantly. Advances in genomic technologies have led to the discovery of genes like MEI1, which play a crucial role in meiosis. However, the population prevalence and pathological mechanisms of human MEI1 variants remains poorly defined. To elucidate the contribution of MEI1 to spermatogenic failure, initial screening for biallelic mutations was conducted in 626 non-obstructive azoospermia (NOA) patients, followed by targeted screening for heterozygous variants in a validation cohort comprising 1,607 well-characterized idiopathic male infertility cases (626 NOA, 799 severe oligoasthenospermia, and 182 terato/asthenozoospermia). Here, we identify MEI1 as a prominent gene associated with non-obstructive azoospermia (NOA), with biallelic pathogenic variants in MEI1 were identified in 12 individuals (1.9%, 12/626). Furthermore, heterozygous MEI1 mutations were identified in 28 patients (0.17%, 28/1607) from the broader infertility screening cohort implicate MEI1 in a wider phenotypic spectrum, broadening its clinical relevance. Critically, micro-TESE uniformly showed no sperm retrieval in individuals carrying biallelic MEI1 mutations, underscoring the imperative for preemptive genetic screening to avoid unnecessary surgical interventions. Mechanistically, these mutations disrupted interactions with key meiotic proteins (ANKRD31, IHO1, REC114, MEI4) in co-immunoprecipitation assays. These results not only elucidate its essential function in meiosis and DSB formation but also support its potential as a molecular marker for non-invasive diagnosis.

PurposeTo investigate the regulatory effect of Super-Activated Platelet Lysate (sPL) on autophagy of periodontal ligament stem cells (PDLSCs) during rat maxillary expansion, with implications for optimizing orthodontic treatment outcomes.MethodsFifty-four male Sprague-Dawley rats were randomized into control, maxillary expansion model, and sPL-treated groups. After expansion model establishment, arch width was monitored, and maxillary samples were collected on days 3, 7, and 14 post-expansion. Histological staining (H&E, TRAP) and immunological assays (IHC/IF) were performed to evaluate periodontal tissue morphology, osteoclast activity, and autophagy-related marker (LC3B, LAMP2, mTOR) expression.ResultsAll rats adapted well after expander installation with no mortality. Arch width increased significantly over time. H&E staining showed narrowed periodontal space, disorganized fibers, and localized bone resorption in the model group on days 3 and 7, with stabilization by day 14. The sPL group exhibited improved tissue morphology by day 7 and stabilization by day 14, though with slightly increased osteoclast activity. TRAP staining revealed elevated osteoclast numbers in the model group on days 3 and 7, decreasing by day 14, whereas the sPL group had fewer osteoclasts initially but more by day 14 (all p < 0.05). IHC indicated increased LC3B expression in both groups on day 3, with significant intergroup differences. By day 7, LC3B decreased in the sPL group but remained elevated in the model group. On day 14, the sPL group showed significantly higher LC3B than the model group. LAMP2 expression mirrored LC3B, while mTOR showed an inverse trend. IF confirmed LC3B expression in CD90-positive cells within the periodontal ligament.ConclusionsPL can modulate PDLSCs autophagy during maxillary expansion, a novel regulatory mechanism that may mitigate alveolar bone complications and shorten orthodontic treatment duration. This finding highlights sPL’s potential as a therapeutic agent in orthodontic practice.

ObjectiveTesticular germ cell tumors (TGCTs), the most prevalent malignancy in males aged 15–40 years, exhibit suboptimal prognosis despite therapeutic advances. This study aimed to identify novel diagnostic biomarkers and elucidate their molecular mechanisms in TGCTs pathogenesis.MethodsThrough integrated bioinformatics analysis of public TCGA(The Cancer Genome Atlas)datasets and clinical specimen validation (n = 14), we screened LINC01272 as a candidate biomarker. RNA immunoprecipitation (RIP) assays were employed to verify the interaction between LINC01272 and fused in sarcoma (FUS). Functional experiments including siRNA-mediated gene silencing, transwell migration/invasion assays, and CCK-8 proliferation tests were performed in TGCTs cell lines (Tcam-2 and NCCIT).ResultsLINC01272 is significantly highly expressed in TGCT tissues. High LINC01272 levels indicate shorter overall and recurrence-free survival periods for patients; the predictive value is particularly significant in the subgroup with low tumor mutation burden. Silencing LINC01272 can inhibit the migration, invasion and proliferation of Tcam-2 and NCCIT cells, and down-regulate N-cadherin and Vimentin, while up-regulating LAMA1. RIP assays confirmed the direct binding of LINC01272 to FUS. FUS silencing can replicate the tumor suppressive effect of LINC01272 deletion, while FUS overexpression can reverse the inhibition of migration, invasion and proliferation caused by LINC01272 silencing.ConclusionWe identified the LINC01272-FUS axis as a critical regulatory pathway in TGCTs progression, providing mechanistic insights for developing liquid biopsy biomarkers and RNA-targeted therapies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12935-025-04095-0.

BackgroundAlthough interest in migraine has increased in recent years, important gaps remain in understanding and optimizing its management. These gaps are particularly pronounced in pediatric migraine, which continues to be understudied.Case reportThis case report demonstrates the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in an 8-year-old male patient with refractory chronic migraine with aura [two to three weekly episodes; visual analog scale (VAS): 5–9; duration of each episode was 24 h]. After discontinuing all prophylactic and abortive medications (except ibuprofen suspensions such as Motrin®), the patient underwent a 28-week taVNS protocol that involved the following phases: a 4-week acute intervention, a 4-week intermission period, a 12-week preventive intervention, and an 8-week follow-up. During the acute intervention phase, the patient’s headache duration decreased by 84.4%, and frequency was reduced to fewer than two episodes/week, with complete aura resolution. The preventive intervention yielded further improvement to fewer than 1 episode/week by week 8 (with a 37.5% reduction in medication use). At final follow-up, the patient maintained a medication-free status with only three mild episodes (VAS: 1–3; duration <30 min) in the last 4 weeks. No adverse events were observed.ConclusiontaVNS was effective and safe in the management of chronic migraine in the reported pediatric patient. These findings suggest the need for further evaluation of this non-pharmacological intervention in pediatric migraine.

ObjectiveThis study aimed to investigate factors influencing embryo transfer success rates after hysteroscopic adhesiolysis in patients with intrauterine adhesions (IUAs).MethodsA retrospective analysis was conducted on the clinical data of 2,447 patients who underwent hysteroscopy and were diagnosed with intrauterine adhesions (IUAs) at our center from January 2023 to December 2023. All patients received adhesion separation surgery and underwent embryo transfer through assisted reproductive technology (ART) after the operation. The patients were divided into the non-pregnancy group (n = 955) and the pregnancy group (n = 1,492) based on pregnancy outcomes. The baseline characteristics, degree of intrauterine adhesions, type and duration of balloon placement, time interval from surgery to embryo transfer, number and type of transferred embryos, quality of transferred embryos, and endometrial thickness before transfer were compared between the two groups. Univariate and multivariate regression analysis methods were performed to identify factors affecting the success rate of embryo transfer.ResultsUnivariate analysis revealed significant associations between pregnancy outcomes and the followinf factors: age (OR = 0.91, p < 0.001), anti-Müllerian hormone (AMH, OR = 1.06, p < 0.001), infertility duration (OR = 0.96, p = 0.044), severe degree of intrauterine adhesion (OR = 0.47, p = 0.001), balloon placement time (OR = 1.01, p = 0.002), pre-transplant endometrial thickness (OR = 1.24, p < 0.001), frozen–thawed embryo transfer (OR = 0.38, p < 0.001), blastocyst transfer (OR = 1.92, p < 0.001), and transfer of high-quality embryos (OR = 1.30, p = 0.002) were significantly associated with pregnancy outcomes. Multivariate analysis further clarified the independent effects of age (OR = 0.92, p < 0.001), severe degree of intrauterine adhesion (OR = 0.31, p = 0.001), endometrial thickness before embryo transfer (OR = 1.19, p < 0.001), blastocyst transfer (OR = 2.03, p < 0.001), and transfer of high-quality embryos (OR = 1.36, p = 0.001) on pregnancy outcomes.ConclusionAge, pre-transplant endometrial thickness, severe intrauterine adhesions, blastocyst transfer, and transfer of high-quality embryos are independent factors associated with pregnancy outcomes following intrauterine adhesion separation and subsequent embryo transfer.

To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. A retrospective case series. An assisted reproductive technology center. The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.

Objective: To investigate whether prior COVID-19 infection and time interval after infection affect the in vitro fertilization (IVF) outcomes. Design: A prospective observational cohort. Setting: Reproductive center in China. Population: Participants recovered from COVID-19 and healthy controls. Methods: All participants received normal IVF treatment. The oocyte and embryo quality as well as pregnancy outcome data were collected and analyzed. Main outcome measure: Oocytes and embryo quality, clinical pregnancy outcomes. Results: The oocyte and embryo quality were comparable between the two groups, including the number of oocytes, 2PN zygotes, fertilization rate, cleavage embryos, day 3 good-quality embryos, blastocyst formation rate, and good-quality blastocysts. Nevertheless, the study group exhibited more degenerated oocytes (0.15±0.40 vs. 0.10±0.33, P=0.035). Further regression analysis indicated that prior COVID-19 infection is positively related to the number of degenerated oocytes (Adjusted β: 0.06, 95% confidential interval (CI): 0 -0.10, P=0.032). No significant differences were observed in clinical pregnancy rate, implantation rate, early miscarriage rate, ectopic pregnancy rate, and ongoing pregnancy rate. Similarly, we observed no difference in oocyte and embryo quality as well as pregnancy outcomes across various post-infection time intervals. Conclusions: Preceding COVID-19 could increase the number of degenerated oocytes. However, it does not affect subsequent pregnancy outcomes. Additionally, post-infection time interval plays no significant role in IVF outcomes.

This study aimed to identify the genetic causes of male infertility and primary ciliary dyskinesia (PCD)/PCD-like phenotypes in three unrelated Han Chinese families. We conducted whole-exome sequencing of three patients with male infertility and PCD/PCD-like phenotypes from three unrelated Chinese families. Ultrastructural and immunostaining analyses of patient spermatozoa and respiratory cilia and in vitro analyses were performed to analyze the effects of SPEF2 variants. Intracytoplasmic sperm injection (ICSI) was administered to three affected patients. We identified four novel SPEF2 variants, including one novel homozygous splicing site variant [NC_000005.10(NM_024867.4): c.4447 + 1G > A] of the SPEF2 gene in family 1, novel compound heterozygous nonsense variants [NC_000005.10(NM_024867.4): c.1339C > T (p.R447*) and NC_000005.10(NM_024867.4): c.1645G > T (p.E549*)] in family 2, and one novel homozygous missense variant [NC_000005.10(NM_024867.4): c.2524G > A (p.D842N)] in family 3. All the patients presented with male infertility and PCD/likely PCD. All variants were present at very low levels in public databases, predicted to be deleterious in silico prediction tools, and were further confirmed deleterious by in vitro analyses. Ultrastructural analyses of the spermatozoa of the patients revealed the absence of the central pair complex in the sperm flagella. Immunostaining of the spermatozoa and respiratory cilia of the patients validated the pathogenicity of the SPEF2 variants. All patients carrying SPEF2 variants underwent one ICSI cycle and delivered healthy infants. Our study reported four novel pathogenic variants of SPEF2 in three male patients with infertility and PCD/PCD-like phenotypes, which not only extend the spectrum of SPEF2 mutations but also provide information for genetic counseling and treatment of such conditions.

Although LINC00313 is dysregulated in several tumors, its role in head and neck squamous cell carcinoma (HNSC) is not fully understood. The aim of this study was to analyze the role of LINC00313 in HNSC. The clinical information and LINC00313 expression data of HNSC were mined from the TCGA/GEO/cbioportal database. The correlation between LINC00313 expression and immune cell infiltration in HNSC tumors was analyzed by bioinformatics and gene enrichment analysis was performed. LINC00313 was silenced in HNSC cell lines, and changes at the genetic and molecular levels were verified through qRT-PCR and Western blotting. The researchers also validated its functional phenotype through a series of cell function experiments. The results showed that overexpression and copy number variation of LINC00313 in HNSC were associated with poorer prognosis. In addition, LINC00313 expression was significantly negatively correlated with immune cell infiltration. Silencing of LINC00313 in HNSC cells significantly reduced the rate of cell migration. LINC00313 may affect the progression of HNSC by regulating epithelial-mesenchymal transition. In conclusion, LINC00313 is a potential biomarker of HNSC prognosis and a potential target for immunotherapy.