Reproductive Biology and Endocrinology最新文献

{"title":"Association between serum Vitamin D levels and sperm DNA fragmentation index in varicocele patients: a retrospective cohort study.","authors":"Tianhong Cai, Rong Zhang, Kai Chen, Jianfeng He, Tenghui Zhan","doi":"10.1186/s12958-025-01438-4","DOIUrl":"10.1186/s12958-025-01438-4","url":null,"abstract":"<p><strong>Objective: </strong>While varicocele is a major cause of male infertility, the role of vitamin D in sperm DNA integrity remains unclear. This study aimed to investigate the association between serum vitamin D levels and sperm DNA fragmentation index (DFI) in varicocele patients.</p><p><strong>Methods: </strong>This retrospective cohort study conducted at Fujian Maternity and Child Health Hospital included 355 varicocele patients aged 18-45 years (June 2021-June 2024). The primary exposure was serum 25-hydroxyvitamin D level, and the primary outcome was DFI. Multiple linear regression models were used to analyze the association between vitamin D and DFI, adjusting for age, BMI, smoking, alcohol consumption, and other confounders.</p><p><strong>Results: </strong>A significant inverse association was found between vitamin D levels and DFI (β = -0.24, 95% CI: -0.28 to -0.19, P < 0.0001). Piecewise linear regression identified a threshold at 25.9 nmol/L, below which the inverse association was more pronounced (β = -1.0, 95% CI: -1.2 to -0.8, P < 0.001).</p><p><strong>Conclusion: </strong>Serum vitamin D levels have been demonstrated to be significantly associated with the rate of sperm DNA fragmentation index in patients with varicocele, particularly at levels below 25.9 nmol/l.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"101"},"PeriodicalIF":4.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of ejaculation frequency on semen parameters and DNA fragmentation: a cross-sectional study.","authors":"Qi Xi, Qingkuo Kong, Xin Lv, Rulin Dai, Yang Yu","doi":"10.1186/s12958-025-01439-3","DOIUrl":"10.1186/s12958-025-01439-3","url":null,"abstract":"<p><strong>Background: </strong>Abnormal sperm quality, particularly high sperm DNA fragmentation levels, is associated with infertility and a higher risk of pregnancy loss. While short abstinence periods may improve semen quality, the specific role of ejaculation frequency (EF) remains unclear. EF refers to the number of times an individual ejaculates within a given period, which is distinct from the abstinence period, defined as the time interval between ejaculations. This study investigates the association between EF and semen quality, including sperm DNA fragmentation.</p><p><strong>Methods: </strong>This cross-sectional study included 1,349 men who underwent semen analysis at a reproductive center between November 2023 and July 2024. The subjects were categorized into three groups based on their self-reported EF over the past four weeks: EF1: <1/week, EF2: ≥1 and <2/week, and EF3: ≥2/week.</p><p><strong>Results: </strong>As EF increased, significant decreases were observed in sperm DNA fragmentation index (DFI) (P < 0.001), semen volume (P = 0.012), sperm concentration (P < 0.001), and total sperm count (P < 0.001). Sperm vitality showed a positive association with EF (P < 0.001), while no association was found between sperm progressive motility and EF. Lower risks of elevated sperm DFI and necrozoospermia were observed in EF2 and EF3 compared to EF1. However, there was no increased risk of oligozoospermia or asthenozoospermia with increased EF.</p><p><strong>Conclusions: </strong>Higher ejaculation frequency is associated with improved sperm vitality and lower DFI without negatively impacting motility. EF should be considered alongside abstinence in male fertility assessments.</p><p><strong>Trial registration: </strong>The study was registered on ClinicalTrials.gov (identifier NCT06127875).</p><p><strong>Date of registration: </strong>November 11th, 2023. Date of enrollment of the first subject: November 11th, 2023.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"100"},"PeriodicalIF":4.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic age and fertility timeline: testing an epigenetic clock to forecast in vitro fertilization success rate.","authors":"Davide Marinello, Marco Reschini, Giorgia Di Stefano, Giorgia Carullo, Maíra Casalechi, Letizia Tarantini, Benedetta Albetti, Valentina Bollati, Paola Viganò, Edgardo Somigliana, Letizia Li Piani","doi":"10.1186/s12958-025-01429-5","DOIUrl":"10.1186/s12958-025-01429-5","url":null,"abstract":"<p><strong>Background: </strong>In the field of in vitro fertilization (IVF), the search for reliable success predictors is ongoing, with novel biomarkers gaining increasing attention. Epigenetic clocks, mathematical models based on DNA methylation (DNAm) patterns, have revolutionized aging research by providing insights into biological aging. However, the magnitude of the benefit of the use of a simplified and non-specific epigenetic clock is still insufficient to claim for its clinical use. We investigated the potential role of epigenetic clocks in predicting IVF success.</p><p><strong>Methods: </strong>This prospective observational study involved 379 women of reproductive age who underwent IVF treatment. On the day of recruitment, blood samples were collected, and genomic DNA was isolated from white blood cells. Epigenetic age was calculated using an algorithm based on the methylation patterns of 5 specific CpG sites and derived by pyrosequencing technique (\"Zbieć-Piekarska2\" model). Epigenetic age acceleration (EPA) was estimated from the residuals of a linear model, with epigenetic age regressed on chronological age. We compared the resulting epigenetic age and EPA between women who achieved a live birth and those who did not, alongside traditional ovarian reserve parameters (antral follicular count AFC; anti-müllerian hormone AMH).</p><p><strong>Results: </strong>Among 379 women, 204 (54%) achieved LB. They were younger, had better ovarian reserve markers, retrieved more oocytes and had lower epigenetic age (36 ± 5 vs. 39 ± 5 years, p < 0.001) with moderate predictive power (area under the curve AUC = 0.652). After adjusting for antral follicular count (AFC), epigenetic age remained significantly associated with live birth (adjusted odds ratio OR = 0.91 per year; p < 0.001), suggesting IVF success is more likely in epigenetically younger women, beyond their ovarian reserve. This association was lost in subgroup analysis by infertility cause. In women aged 31-35, epigenetic age and EPA were the best predictors (AUC = 0.637). Combining epigenetic age with ovarian reserve markers slightly improved predictive accuracy (AUC = 0.692 with AFC, 0.693 with AMH) over chronological age alone (AUC = 0.672).</p><p><strong>Conclusions: </strong>Epigenetic clocks may enhance IVF success prediction, particularly in women between 31 and 35. Our findings support the need for further research in this area and emphasize the importance of developing epigenetic models specifically tailored to fertility outcomes.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"99"},"PeriodicalIF":4.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycystic ovary syndrome and excessive body weight impact independently and synergically on fertility treatment outcomes.","authors":"Emídio Vale-Fernandes, Mafalda V Moreira, Raquel L Bernardino, Daniela Sousa, Raquel Brandão, Carla Leal, Márcia Barreiro, Mariana P Monteiro","doi":"10.1186/s12958-025-01434-8","DOIUrl":"10.1186/s12958-025-01434-8","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) and obesity can both disrupt reproductive function. However, the extent to which obesity contributes to PCOS manifestations is not very clear. This study aimed to disentangle the relative contributions of PCOS and obesity for reproductive dysfunction in women undergoing in vitro fertilization (IVF).</p><p><strong>Methods: </strong>A total of 129 women undergoing IVF treatments were recruited. Women were allocated into four groups according to body mass index (BMI) and PCOS diagnosis: normal-weight controls (n = 33; 21.70 ± 1.85 kg/m²), overweight/obesity controls (n = 28; 28.35 ± 3.05 kg/m²), normal-weight PCOS (n = 31; 21.92 ± 1.95 kg/m²), and overweight/obesity PCOS (n = 37; 31.67 ± 5.03 kg/m²). Circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), glucose and insulin were measured in all groups, while insulin resistance was assessed by the Homeostatic Model (HOMA-IR). Additionally, on the oocyte retrieval day, ∆4-androstenedione, testosterone, progesterone and sex hormone-binding globulin (SHBG), were measured in plasma and follicular fluid (FF). IVF outcomes evaluated included the number of oocytes retrieved, oocyte immaturity, as well as fertilization and blastocyst formation rates. A multivariate analysis was performed to determine the independent effects of PCOS and obesity for reproductive and metabolic parameters.</p><p><strong>Results: </strong>Women with PCOS presented significantly higher AMH levels, LH: FSH ratio, and lower FF progesterone levels, confirming these as PCOS-specific signatures regardless of BMI. In contrast, women with overweight/obesity had lower plasma and FF SHBG levels and greater HOMA-IR, independently of PCOS. Furthermore, ∆4-androstenedione and testosterone levels in plasma and FF were significantly higher in women with PCOS and overweight/obesity as compared to normal-weight women with PCOS. Despite the higher oocyte retrieval rates in women with PCOS, no differences in oocyte immaturity, fertilization and blastocyst formation rates were observed.</p><p><strong>Conclusions: </strong>PCOS and obesity independently disrupt female reproductive function suggesting that features associated with each condition may differ. Furthermore, our study shows that obesity exacerbates hyperandrogenism in women with PCOS, highlighting a synergistic detrimental impact on female reproductive function.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"97"},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early androgen activity after birth determines the hypothalamic expression of androgen and estrogen receptors in adulthood in female but not in male rats.","authors":"Rocío García-Úbeda, Jose Manuel Fernandez-Garcia, Ulises Primo, Daniela Grassi, Antonio Ballesta, Maria Angeles Arevalo, Paloma Collado, Helena Pinos, Beatriz Carrillo","doi":"10.1186/s12958-025-01430-y","DOIUrl":"10.1186/s12958-025-01430-y","url":null,"abstract":"<p><p>Gonadal steroids are involved in the organization and programming of several neural systems. The main objective of this study was to determine whether androgen activity in the early postnatal stage influenced the long-term expression of androgen and estrogen receptors in the hypothalamus. Androgen receptors (AR) and the main metabolic pathways of testosterone were inhibited using Flutamide, an AR inhibitor, Letrozole, an aromatase inhibitor, or Finasteride, a 5-alpha-reductase inhibitor, during the first five days of life in male and female Wistar rats. Hypothalamic hormonal receptors AR, and estradiol receptors (ER)α, and ERβ were analyzed by qPCR, and circulating hormone levels (testosterone, DHT, and estradiol) were measured using ELISA assay at P90. The inhibition of AR, 5α-reductase or aromatase did not alter the hypothalamic levels of hormone receptors in males. However, in females, blocking the androgen receptor increased the ERβ, while the inhibition of 5α-reductase decreased the ERα and the inhibition of aromatase increased AR and ERβ hypothalamic mRNA levels. Moreover, testosterone plasma levels decreased significantly in females independent of whether the AR, 5α-reductase, or aromatase were inhibited. However, only the inhibition of aromatase decreased circulating testosterone levels in males. Furthermore, higher plasma testosterone and DHT levels were detected in males compared to females. Our results highlight the influence of androgen activity during the first days of life in females on the long-term expression of androgen and estrogen receptors in the hypothalamus, which reaffirms the importance of studying both sexes to accurately explain the processes that determine the programming of neural systems during development.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"98"},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy imbalance in oPOI ovarian granulosa cells is linked to reduced glucose bioavailability and metabolism.","authors":"Weronika Marynowicz, Paulina Głód, Dawid Maduzia, Justyna Gogola-Mruk, Anna Ptak","doi":"10.1186/s12958-025-01426-8","DOIUrl":"10.1186/s12958-025-01426-8","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI), affecting approximately 1% of women under 40, is associated with impaired fertility. Occult POI (oPOI), an initiating form, is more challenging to detect but still allows potential success with IVF. Recent studies suggest a possible link between granulosa cell (GC) mitochondrial dysfunction and POI, as mitochondria are critical for energy production and reproductive function.</p><p><strong>Methods: </strong>We recruited 81 women undergoing IVF which included: 25 women with oPOI defined as a low anti-Müllerian hormone (AMH) level (≤ 1.1 ng/mL) and under the age of 40 without raised follicle-stimulating hormone (FSH) levels and 56 healthy women (male or tubal factor infertility). Molecular analysis of GCs and CCs involved RT-qPCR and functional assays, including Seahorse metabolic profiling, fluorometric/luminescent enzyme activity tests, and mitochondrial fluorescent staining.</p><p><strong>Results: </strong>We found that cumulus cells (CCs) from oPOI women showed reduced energy capacity. Similarly, GCs shifted toward glycolysis in oPOI, leading to lower ATP production. Despite similar glucose levels in FF between groups, oPOI CCs exhibited impaired glucose uptake and metabolism, with decreased GLUT1 and reduced hexokinase 2 (HK2) activity. In GCs, reduced GLUT1 but increased HK2 gene expression suggests compensatory metabolic reprogramming to maintain energy balance through enhanced glycolysis. Additionally, oPOI women had a lower level of estradiol, despite having a normal FSH level and a decreased estradiol/oocyte count.</p><p><strong>Conclusions: </strong>This study indicated that in the case of oPOI, disruption may extend beyond the ovaries to impact the entire HPO axis. Furthermore, reduction of ATP production is connected with lower glucose uptake and may have implications for fertility in oPOI patients. It also highlights the potential for therapeutic strategies focused on improving glucose metabolism and mitochondrial biogenesis.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"96"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapamycin reduces DNA damage of in vitro matured oocytes by promoting Rad51-mediated homologous recombination.","authors":"Qiyu Yang, Ying Chen, Jiayu Huang, Junying Tang, Lixia Zhu, Jingyu Li, Chao Tong","doi":"10.1186/s12958-025-01428-6","DOIUrl":"10.1186/s12958-025-01428-6","url":null,"abstract":"<p><strong>Background: </strong>The quality of in vitro matured (IVM) oocytes remains inferior to that of in vivo matured oocytes, likely due to DNA damage induced by the in vitro environment. Although rapamycin has been shown to improve the developmental competence of IVM oocytes by reducing DNA double-strand breaks (DSBs), the underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>Immature oocytes from 6 ~ 8-week-old ICR female mice were subjected to IVM with or without rapamycin. After 14 ~ 16 h, the maturation rate, DNA DSB levels, and subsequent developmental competence of IVM oocytes were assessed. The homologous recombination (HR) and non-homologous end joining (NHEJ) pathways were selectively inhibited using RAD51 and DNA-PK inhibitors, respectively, to elucidate the predominant DNA damage repair pathway during IVM and investigate the effects of rapamycin on this process.</p><p><strong>Results: </strong>Embryos derived from the rapamycin-treated group exhibited significantly higher 2PN and cleavage rates compared to the control group. MII oocytes cultured with rapamycin showed reduced γH2AX immunofluorescence intensity, indicating lower DNA damage levels. Additionally, the expression levels of RAD51 and DNAPK were elevated in rapamycin-treated oocytes. Inhibition of RAD51 significantly reduced the maturation rate and increased DNA damage levels, whereas DNAPK inhibition had no effect on oocyte development or quality. Importantly, the beneficial effects of rapamycin on IVM oocytes were diminished under RAD51 inhibition.</p><p><strong>Conclusion: </strong>Rapamycin improves the developmental competence of IVM oocytes by enhancing the RAD51-mediated HR pathway, thereby enhancing DNA stability.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"93"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effectiveness of nutritional supplements in improving polycystic ovary syndrome in women: a systematic review and network meta-analysis.","authors":"Guanhua Zhao, Yuxin Fan, Ruixia Li, Yu Huang, Wenjuan Li, Yanhong Zhao, Mengdi Zhou, Jianchang He","doi":"10.1186/s12958-025-01409-9","DOIUrl":"10.1186/s12958-025-01409-9","url":null,"abstract":"<p><strong>Background: </strong>Nutritional supplements are known to ameliorate polycystic ovary syndrome (PCOS) and have been shown to modulate endocrine and metabolic markers, oxidative stress markers and inflammatory biomarkers in patients with PCOS. A variety of nutritional supplements have been applied in clinics, but a more comprehensive ranking of their efficacy has not yet been investigated.</p><p><strong>Objectives: </strong>To assess the comparative effectiveness of nutritional supplements in women with PCOS.</p><p><strong>Methods: </strong>A systematic search was conducted across PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) that met the inclusion criteria up to October 12, 2023. We performed a network meta-analysis (NMA) to evaluate the effectiveness of various nutritional supplements on different indicators of PCOS by synthesizing both direct and indirect evidence from the trials.</p><p><strong>Results: </strong>Seventy-nine RCTs involving 5,501 participants were enrolled in the NMA. It suggested that chromium was notably effective in improving follicle-stimulating hormone levels, total antioxidant capacity, and very low-density lipoprotein levels. Soy isoflavones were more beneficial for enhancing glutathione levels and reducing malondialdehyde levels. Inositol significantly decreased total cholesterol and triglyceride levels, while curcumin was most effective in improving low-density and high-density lipoprotein cholesterol levels. Additionally, Omega-3 was superior in reducing homeostatic model assessment of insulin resistance levels. No significant differences were observed in total testosterone, sex hormone-binding globulin, dehydroepiandrosterone, high-sensitivity C-reactive protein, and plasma nitric oxide levels between the supplements and placebo.</p><p><strong>Conclusions: </strong>Chromium, inositol, and Omega-3 were found to be beneficial for improving lipid profile. For improving obesity, sex hormone levels, inflammatory factors and oxidative stress indicators of PCOS patients, carnitine, chromium, and soy isoflavones are effective options, respectively. These findings confirm that nutritional supplements can effectively alleviate PCOS symptoms, potentially providing valuable guidance for the clinical selection of appropriate nutritional interventions.</p><p><strong>Trial registration: </strong>PROSPERO registration number CRD42023483534.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"94"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual-drug strategy to enhance the function of cryopreserved ovaries by promoting revascularization and inhibiting follicle over-activation.","authors":"Lingyu Li, Jian Yang, Longzhong Jia, Jing Liang, Kaixin Cheng, Xuebing Yang, Lu Mu, Ge Wang, Kaiying Geng, Qiuxian Hu, Xueqiang Xu, Zhen Li, Guoliang Xia, Ting Guo, Jiawei Zhang, Yan Zhang, Hua Zhang","doi":"10.1186/s12958-025-01422-y","DOIUrl":"10.1186/s12958-025-01422-y","url":null,"abstract":"<p><strong>Background: </strong>Ovarian tissue cryopreservation and transplantation (OTCT) is a promising approach for fertility preservation. However, significant follicle loss after transplantation challenges long-term reproductive recovery. Although primordial follicle loss and ischemic damage are known contributors, the underlying mechanisms and effective strategies to mitigate these damages are still lacking.</p><p><strong>Methods: </strong>Ovarian tissues from wild-type or Tek-CreER^T2;mTmG female mice were cryopreserved using vitrification. Follicle dynamics after OTCT were analyzed through histology, proteomics, and high-resolution imaging. To assess protective effects, cryopreserved ovaries were treated with 500 nM rapamycin (Rapa), an inhibitor of primordial follicle activation; 5 ng/mL vascular endothelial growth factor A (VEGFA), which promotes angiogenesis; or both (Cryo + VRCS, VEGFA-Rapa Combination Strategy). DMSO or H₂O served as controls. Grafts were collected at 3, 7, 14, and 120 days post-transplantation, with measurements of vascular density, tip cell density, follicle activation, and remaining follicles. Oocyte quality was evaluated via in vitro fertilization, and graft lifespan was estimated through estrous cycle monitoring.</p><p><strong>Results: </strong>Our study observed a rapid decline in follicle numbers shortly after transplantation in a mouse model. Proteomic analysis and high-resolution 3D imaging revealed that this depletion was primarily due to damage to tip cells, which are crucial for angiogenesis, and the overactivation of dormant primordial follicles. Damage to tip cells compromised vascular reconstruction, leading to ischemic injury, while mechanical handling during tissue isolation and cryopreservation triggered excessive follicle activation. We implemented a combination therapy using rapamycin to inhibit follicle activation and VEGFA to promote angiogenesis prior to transplantation. This approach significantly improved follicle survival, extended reproductive function, and enhanced oocyte quality.</p><p><strong>Conclusion: </strong>Our study provides a practical strategy for preserving the reproductive potential of cryopreserved ovarian tissues by simultaneously targeting vascular integrity and follicle stability through the dual drug strategy of VEGFA and rapamycin combine treatment.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"95"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term impact of tirzepatide on metabolic hypogonadism and body composition in patients with obesity: a controlled pilot study.","authors":"Sandro La Vignera, Rossella Cannarella, Vincenzo Garofalo, Andrea Crafa, Federica Barbagallo, Rosita A Condorelli, Aldo E Calogero","doi":"10.1186/s12958-025-01425-9","DOIUrl":"10.1186/s12958-025-01425-9","url":null,"abstract":"<p><strong>Background: </strong>Tirzepatide (TZP), a dual agonist of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has recently been introduced in Italy for the treatment of obesity. Obesity is frequently associated with metabolic hypogonadism, which is characterized by low testosterone levels and normal low levels of gonadotropin. This condition exacerbates metabolic dysfunction and increases the risk of type 2 diabetes mellitus (DM). This study aims to evaluate the effects of TZP on metabolic hypogonadism in patients with obesity.</p><p><strong>Methods: </strong>Male patients with obesity and metabolic hypogonadism were enrolled. Exclusion criteria included recent use of medications for hypertension, dyslipidemia, DM, anti-androgens, or hyperprolactinemia. All participants followed a hypocaloric diet and engaged in 20 min of daily brisk walking. Patients were allocated to one of the following treatment groups: Group A received 2.5 mg of TZP weekly for the first month, with the dose increased to 5 mg from the second month; Group B received no pharmacological treatment: Group C received transdermal testosterone. Clinical evaluations were conducted at 2 months including assessment of body composition, the Binge Eating Scale (BES), 5-item International Index of Erectile Function (IIEF-5) questionnaire to evaluate erectile dysfunction (ED), and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total testosterone (TT), and 17β-estradiol (E₂). Free (fT) and bioavailable testosterone (bioT) were calculated using the Vermeulen formula.</p><p><strong>Results: </strong>A total of 83 patients with obesity (mean age 55.3 ± 5.5 years) were included in the study, divided into three groups: Group A (28 patients, mean age 56.3 ± 4.7 years), Group B (30 patients, mean age 55.1 ± 5.2 years), and Group C (25 patients, mean age 54.0 ± 6.5 years). At baseline, significant differences were observed in waist circumference (WC), which was higher in Group B, as well as in the BES score, lean mass (LM), and serum LH levels, all of which were higher in Group A. After 2 months, Group A showed significantly greater reductions in body weight, WC, BES score, and fat mass, along with a notable increase in LM and IIEF-5 score compared to Groups B and C. Additionally, Group A exhibited significantly higher serum levels of LH, FSH, SHBG, TT, fT, and bioT, while E₂ levels were significantly lower than both Groups B and C.</p><p><strong>Conclusion: </strong>The results of this study suggest that TZP is effective in improving both metabolic parameters, ED, and gonadal hormone levels in patients with obesity and metabolic hypogonadism. These findings position TZP as a promising treatment for obese patients with functional hypogonadism arising from metabolic-related alterations.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"92"},"PeriodicalIF":4.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}