Search Results (75)

Deoxynivalenol (DON) is a common mycotoxin linked to ovarian oxidative stress, toxicity, and reduced reproductive performance. Fermented Chinese chive is known for its antioxidant properties and potential reproductive benefits, but their individual and combined effects on ovarian function remain unclear in post-pubertal mice. In this study, a 21-day oral gavage model in female Kunming mice was used to evaluate the effects of DON (2 mg/kg/day), fermented Chinese chive extract (LEEK; 0.2 mL/day), and their combined exposure (LKDON) on ovarian physiology, oocyte quality, and ovarian transcriptomic responses. The results showed that DON exposure significantly reduced the zygote cleavage rate, increased intracellular reactive oxygen species levels, and disrupted oocyte mitochondrial membrane potential. While histological examination revealed disturbed follicular architecture. Transcriptomic hub gene analysis showed that DON exposure down-regulate the key associated with innate immune responses and motile cilia/axonemal structure, including Rsph4a, Drc1, Zmynd10, Hydin, and Tmem212. In contrast, LEEK alone was associated with immunomodulatory upregulated genes, including Il5, Cd27, and Crp. Interestingly, LKDON and DON comparison revealed upregulation of a motile cilia/axoneme gene network (Dnah5, Dnah11, Tekt1, Zmynd10, Cfap44, and Spag6l), rather than a global reversal of DON-induced changes. Overall, finding suggest that DON disrupts ovarian immune and structural pathways, while fermented Chinese chive provides partial protection by modulating specific biological processes. Further studies are needed to confirm the underlying mechanisms. Full article

The transport of metabolites across biological membranes is vital for normal cellular functions, including nutrient uptake, homeostasis, and toxin efflux. In eukaryotes, mitochondrial transporters in the inner mitochondrial membrane (IMM) play a pivotal role in energy production, metabolism, and the biosynthesis of a wide range of compounds. While functional assignments exist for over half of the mitochondrial transporters, emerging high-throughput methodologies underscore the need for reassessment and expansion of the current knowledge, particularly as evidence suggesting functional redundancy and substrate promiscuity has emerged. In this study, we investigated the substrate specificity of five yeast mitochondrial transporters—Crc1 (YOR100c), Ctp1 (YBR291c), Oac1 (YKL120w), Pet9 (YBL030c), and Yhm2 (YMR241w)—via heterologous gene expression in Xenopus laevis oocytes and liquid chromatography-mass spectrometry (LC-MS)-based transport assays. We used two substrate mixtures: a 17-compound organic acid mix and a ¹³C-labeled yeast metabolite extract. Our results revealed broader substrate specificities than previously reported, as partially supported by substrate docking simulations. Pet9 transported several organic acids and amino acids, while Yhm2 showed uptake of nine amino acids and fumaric acid. Additional promiscuous transport activity was observed for Crc1, indicating that these proteins may have more extensive metabolic roles than previously known. This study advances the understanding of yeast mitochondrial transporter function, demonstrating redundancy and broad substrate specificity among mitochondrial carriers. It highlights the importance of utilizing in vivo heterologous systems and physiologically relevant substrate mixtures to elucidate transporter functionality. Full article

Background: Preserving fertility in young women with cancer is crucial for comprehensive care. Based on GBD 2023 estimates, approximately 1000 women aged 15–39 are diagnosed with haematological malignancies annually in Italy. Guidelines recommend timely fertility preservation (FP) counselling for all at-risk patients, yet real-world access data remain limited. Methods: This multicentre, retrospective observational study analysed FP counselling for women aged 15–39 with haematological malignancies from 2015 to 2023. Counselling data were extracted from the Italian Assisted Reproductive Technology Registry (IARTR). This data collection system, known as PreFerIta, was developed within a project supported by the Italian Ministry of Health to collect data on Fertility Preservation (FP) treatments in oncology patients and/or those at risk of iatrogenic infertility, provided in seven specialised ART centres across Italy. The PreFerIta database includes data on both oocyte cryopreservation and ovarian tissue cryopreservation. Annual visits were related to the estimated regional incidence of new haematological malignancies (GBD 2023). Counselling-to-incidence ratios, absolute/relative gaps, and 95% confidence intervals (CIs) were calculated. Results: From 2015 to 2023, an estimated 4473 new haematological malignancies occurred in the catchment regions. Concurrently, 1200 FP counselling visits were recorded. While incidence modestly declined, counselling activity remained high. The counselling-to-incidence ratio increased from 17.33% in 2015 to 31.92% in 2018, stabilising between 26% and 31% thereafter (30.98% in 2023). The relative counselling gap decreased from 82.67% to 69.02%. These ratios represent lower-bound estimates of access to specialised oncofertility consultations. Conclusions: In this Italian network, approximately one in four to one in three incident haematological malignancies in young women were associated with specialised FP counselling. This reflects a substantial integration of oncofertility services into haematology care, highlighting opportunities to further strengthen referral pathways and achieve full guideline concordance. Full article

Background and Objectives: The Mediterranean diet is traditionally linked to metabolic balance and improved reproductive health. However, dietary patterns in Mediterranean regions have progressively shifted toward more Westernized models, particularly among women of reproductive age, raising concerns about declining adherence to this historically protective diet. Objective: To assess adherence to the Mediterranean diet among women undergoing assisted reproductive technology (ART) and to explore possible associations with ovarian response and clinical outcomes. Materials and Methods: This prospective observational cohort study was conducted at a reproductive clinic in Sicily between 1 June and 31 July 2022. One hundred women aged 18–40 years undergoing infertility assessment and scheduled for controlled ovarian stimulation were enrolled. Mediterranean diet adherence was evaluated using the validated 14-item MEDAS questionnaire during the first clinical visit. ART-related outcomes, including ovarian response and pregnancy rates, were extracted from medical records. Results: The mean MEDAS score was 7.6 ± 1.2: 93% of women showed moderate adherence, 3% high adherence, and 4% low adherence. No significant associations were found between MEDAS score, and total oocytes retrieved, MII oocytes, or clinical pregnancy. Conclusions: Despite living in a traditionally Mediterranean area, participants demonstrated only moderate adherence to the Mediterranean diet. Although no associations with single-cycle ART outcomes emerged, the findings underscore the need for structured nutritional counseling to reinforce sustained adherence and support long-term reproductive health. Full article

Sperm proteases are involved in several gamete interaction events leading to fertilization. This report presents a detailed analysis of the expression and localization of serine protease PRSS38 in human and in mouse spermatozoa and its involvement in fertilization-related events, using bioinformatics, cellular, biochemical, molecular, and functional approaches. Bioinformatics analyses included genomics and data analysis, prediction of protein subcellular localization and post-translational modifications, Self-Organizing Maps (SOMs) unsupervised training with other serine proteases, protein modeling (AlphaFold), and genetic variant analysis. For cellular, biochemical, and functional studies, human semen samples were obtained from healthy normozoospermic volunteers, and cauda epididymal sperm were collected from adult Balb-c/C57 mice. PRSS38 presence was detected in human and mouse sperm protein extracts by Western immunoblotting. Sperm PRSS38 subcellular localization was determined by fluorescence immunocytochemistry. Human sperm–oocyte interaction events were assessed by means of the mouse Cumulus Penetration Assay (CPA) using mouse COCs, the Human Hemizona Assay (HZA), and the ZP-free hamster egg Sperm Penetration Assay (SPA). Mouse sperm–oocyte interactions were evaluated by means of in vitro fertilization (IVF) with COCs and denuded oocytes. PRSS38 is proposed to be a GPI-anchored serine protease (active site: His-100, Asp-150, and Ser-245) based on bioinformatics analyses. Using commercial antibodies, protein forms of the expected Mr (human: 31 kDa; mouse: 32 and 24 kDa) were specifically immunodetected in protein sperm extracts. Immunocytochemical analysis revealed a specific PRSS38 signal in the human sperm acrosomal region, equatorial segment, and flagellum. Mouse sperm PRSS38 was immunolocalized in the equatorial segment and hook. Human sperm preincubation with specific antibodies resulted in inhibition (p < 0.05) of CPA, HZA, and SPA. Mouse sperm preincubation with PRSS38 antibodies impaired (p < 0.05) homologous IVF using COCs and denuded oocytes. Genetic variants affecting residues involved in the GPI anchor and the catalytic triad were found in individuals from the general population whose PRSS38 protease function could be altered. This study provides, for the first time, an integrated analysis of PRSS38 in human and mouse sperm, contributing to our understanding of mammalian fertilization and male infertility. Full article

Oxidative stress compromises follicle survival during in vitro culture. Natural antioxidants may reduce cellular damage and preserve tissue integrity. This study evaluated the ethanolic extract from Punica granatum L. (EE-PG) on bovine ovarian tissue cultured in vitro. Bovine ovarian (n = 24) fragments were cultured for 6 days in αMEM⁺ medium with or without EE-PG at 10, 50, or 100 µg/mL. At the end of the in vitro culture, the medium was used to evaluate antioxidant capacity (DPPH and ABTS assays), while the fragments were collected for morphological and biochemical analyses. HPLC-UV-Vis confirmed the presence of α-punicalagin in the pure EE-PG. At 100 µg/mL, EE-PG showed the strongest effects: it had higher antioxidant capacity, preserved follicle morphology and ultrastructure, and promoted follicle activation. At 50 and 100 µg/mL, the extract also reduced malondialdehyde (MDA) and increased thiol levels, indicating protection against lipid peroxidation. In contrast, 10 µg/mL had little effect. Follicle and oocyte diameters were not significantly altered, but the collagen I/III ratio increased at higher concentrations, suggesting extracellular matrix remodeling. Together, these findings demonstrate that EE-PG protects bovine preantral follicles from oxidative stress, maintains redox balance, and preserves tissue integrity. These results reinforce the potential of Punica granatum L. extract as a natural antioxidant in reproductive biotechnologies and fertility preservation. Full article

Background/Objectives: With increasing survival rates in pediatric oncology, late effects, such as therapy-induced infertility, are becoming more relevant. This study evaluated the management of fertility preservation in children and adolescents with cancer at the Medical University Innsbruck between 2000 and 2018. Methods: In this retrospective monocentric study, 552 patients (0–17 years) receiving chemotherapy were analyzed. Data was extracted from the Clinical Information System and the cryopreservation database. The assessed main variables included pubertal status, sex hormone levels, and use of fertility preservation methods. Results: Fertility preservation was documented in 6.5% of patients, more frequently in males (8.9%) than females (3.2%). Sperm cryopreservation was performed in twenty-eight males, ovarian tissue cryopreservation in six females, and oocyte cryopreservation in three. Pubertal status at diagnosis was recorded in 4.9% of patients and hormone levels in 29.7%. Conclusions: The findings highlight significant gaps in systematic fertility preservation, particularly in female patients. Consistent assessment of pubertal and hormonal parameters at diagnosis is essential to inform decision-making. Standardized procedures and closer interdisciplinary collaboration are needed to ensure equitable access to fertility preservation and safeguard long-term quality of life. Full article

Ovarian follicular fluid (FF) is a metabolically active and biomarker-rich medium that mirrors the oocyte microenvironment. Its analysis is increasingly recognized in infertility diagnostics and assisted reproductive technologies (ART) for assessing oocyte competence, understanding reproductive disorders, and guiding personalized treatment. However, FF’s high viscosity, complex composition, and biochemical variability challenge reproducibility in sample preparation and molecular profiling. Sonication-based extraction has emerged as an effective approach to address these issues. By exploiting acoustic cavitation, sonication improves protein solubilization, metabolite release, and lipid recovery, while reducing solvent use and processing time. This review synthesizes recent advances in sonication-assisted FF analysis across proteomics, metabolomics, and lipidomics, emphasizing parameter optimization, integration with advanced mass spectrometry workflows, and emerging applications in microfluidics, automation, and point-of-care devices. Clinical implications are discussed in the context of enhanced biomarker discovery pipelines, real-time oocyte selection, and ART outcome prediction. Key challenges, such as preventing biomolecule degradation, standardizing protocols, and achieving inter-laboratory reproducibility, are addressed alongside regulatory considerations. Future directions highlight the potential of combining sonication with multi-omics strategies and AI-driven analytics, paving the way for high-throughput, standardized, and clinically actionable FF analysis to advance precision reproductive medicine. Full article

Hyperuricemia, characterized by elevated serum uric acid levels, is a major risk factor for gout and kidney disease. This study evaluated the antihyperuricemic effects of Cornus officinalis extract (COE) using urate transporter 1 (URAT1)-expressing oocytes and a hyperuricemia rat model. COE effectively inhibited uric acid absorption by modulating URAT1, with an IC₅₀ value of 3.24 µg/mL. In the hyperuricemia model, COE administration (100 and 200 mg/kg) significantly reduced serum uric acid levels and increased urinary uric acid excretion. The primary constituents of COE, morroniside (MO) and loganin (LO) exerted similar effects, with MO exhibiting potent inhibition of uric acid absorption even at low concentrations. Kidney tissue analysis revealed a reduction in blood urea nitrogen (BUN) levels, indicating improved renal function. Liver function parameters (ALT, AST, and LDH) remained unchanged, suggesting an absence of hepatotoxicity. Ultra-high-performance liquid chromatography with charged aerosol detection (UHPLC-CAD) analysis identified MO (17.8 mg/g), LO (9.8 mg/g), and cornin (1.4 mg/g) as the principal components of COE. These findings suggest that COE enhances uric acid excretion via URAT1 regulation and exerts renoprotective effects, highlighting its potential as an antihyperuricemic agent. Furthermore, MO and LO were identified as the primary active constituents, and COE appears to be a promising therapeutic candidate with a favorable safety profile. Full article

Extracts of aromatic medicinal plants have been extensively studied regarding their numerous bioactivities. However, despite being highly used by humans, studies on the safety of these extracts for animal use are scarce. In this study, we aim to contribute to the determination of the safety profile of plant extracts by focusing on the reproductive toxicity of hydrolates (a by-product of essential oils production) of four endogenous Portuguese plants—Cistus ladanifer, Cupressus lusitanica, Helychrisium italicum, and Thymbra capitata—by studying their effects on bovine oocytes and spermatozoa. To achieve our aims, we determined the oocyte maturation and viability rate in the bovine in vitro maturation test (bIVM) and the bovine sperm viability using the eosin–nigrosin test, in the presence of five concentrations of each hydrolate at half-log intervals (% v/v of culture media). We found that hydrolates did not affect oocyte maturation or viability (maximum concentration tested: 0.2%, v/v). Regarding the sperm viability test, we found that T. capitata and C. ladanifer hydrolates impaired sperm viability (p < 0.05) (maximum concentration tested: 0.2%, v/v), in comparison with the negative control. In summary, we found that H. italicum and C. lusitanica hydrolates were safe regarding oocyte maturation, oocyte viability, and sperm viability, being candidates to be included in bovine husbandry as feeding additives. Full article

This study aimed to investigate the glycaemic control potential and modulation of GABA-induced chloride currents (I_GABA) of H. revolutum and the possible bioactive xanthones. Fractions from the leaf and stem extracts (dichloromethane and methanol) were assessed for in vitro α-glucosidase-inhibitory potential and their ability to modulate I_GABA (GABAergic effect) through GABA_A receptors heterologously expressed in Xenopus oocytes. Xanthones 4-hydroxy-2,3-dimethoxy-9H-xanthen-9-one (1), 3-hydroxy-2,4-dimethoxy-9H-xanthen-9-one (2) and trans-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-5-methoxy-2,3-dihydro-7H-[1,4]dioxino[2,3-c]xanthen-7-one (3) were isolated from the stem and tested in the GABA_A receptors assay, but only 3 was assessed for α-glucosidase-inhibitory action. Compared to acarbose (IC₅₀ = 6.16 µM), 3 showed a mild to moderate α-glucosidase-inhibitory activity (IC₅₀ = 45.1 µM), which may be attributed to the absence of a hydroxyl group at its xanthone core. Isomeric compounds 1 and 2 significantly enhanced I_GABA with similar efficacy, while 3 was inactive, which may be attributed to its notable structural difference (cyclic ether substitution) compared to compounds 1 and 2. H. revolutum stem contains xanthones with α-glucosidase-inhibitory potential, which also enhance I_GABA and could be further studied as a medicinal plant for managing GABA_A receptor-mediated mental disorders and/or diabetes. Full article

The efficacy of Lagerstroemia speciosa (banaba) leaf extract (BLE), policosanol (POL), and their combination (BLE+POL) was evaluated in zebrafish (Danio rerio) against high cholesterol (HC)- and galactose (HG)-induced metabolic stress and organ toxicity. After 12 weeks of dietary intervention, BLE+POL significantly reduced HC+HG-augmented weight gain and improved hepatic and nephromegaly. Compared with BLE or POL alone, the combined intake of BLE+POL more effectively alleviated dyslipidemia and blood glucose levels. Likewise, BLE+POL effectively reduced blood malondialdehyde (MDA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and boosted plasma sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. Histological outcomes suggest that BLE+POL has higher efficacy than either BLE or POL in mitigating HC+HG-induced fatty liver changes, hepatic inflammation, kidney senescence, and reactive oxygen species (ROS) production. Consistently, BLE+POL augmented the spermatozoa counts in the testes, enhanced mature vitellogenic oocytes in ovaries, and protected them from the HC+HG-induced oxidative stress. Compared with either BLE or POL, a combined intake of BLE+POL displayed a superior effect in inhibiting the apoptosis and accumulation of lipid peroxidation species 4-hyrdoxynonenal (4-HNE) in the brain. A combined intake of BLE+POL exhibited a pronounced impact than the BLE and POL alone and can be utilized as an effective formulation to counteract the HC+HG-induced events. Full article

Bacterial communities within the female upper genital tract may influence the risk of ovarian cancer. In this retrospective cohort pilot study, we aim to detect different communities of bacteria between ovarian cancer and normal controls using topic modeling, a natural language processing tool. RNA was extracted and analyzed using the VITCOMIC2 pipeline. Topic modeling assessed differences in bacterial communities. Idatuning identified an optimal latent topic number and Latent Dirichlet Allocation (LDA) assessed topic differences between high-grade serous ovarian cancer (HGSOC) and controls. Results were validated using The Cancer Genome Atlas (TCGA) HGSOC dataset. A total of 801 unique taxa were identified, with 13 bacteria significantly differing between HGSOC and normal controls. LDA modeling revealed a latent topic associated with HGSOC samples, containing bacteria Escherichia/Shigella and Corynebacterineae. Pathway analysis using KEGG databases suggest differences in several biologic pathways including oocyte meiosis, aldosterone-regulated sodium reabsorption, gastric acid secretion, and long-term potentiation. These findings support the hypothesis that bacterial communities in the upper female genital tract may influence the development of HGSOC by altering the local environment, with potential functional implications between HGSOC and normal controls. However, further validation is required to confirms these associations and determine mechanistic relevance. Full article

Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article

This study aimed to compare sperm parameters and reproductive outcomes after sperm selection using microfluidic chips versus conventional techniques (swim-up/density gradients). A systematic review and meta-analysis were performed after the extraction of relevant data from thirty-nine studies that met the inclusion criteria. Mean difference or odds ratio was calculated for each outcome. The analysis revealed that sperm selection using microfluidics yields lower sperm DNA fragmentation (MD = −9.98 [−13.19, −6.76], p < 0.00001), increased progressive motility (MD = 14.50 [7.84, 21.71], p = 0.04), total motility (MD = 10.68 [6.04, 15.31], p < 0.00001) and morphology (MD = 1.41 [0.67, 2.16], p = 0.0002). Significant differences were also found in the fertilization rate/MII oocyte microinjected (OR = 1.22 [1.01, 1.46], p = 0.04), implantation rate/embryo transfer (ET) (OR = 4.51 [1.42, 14.37], p = 0.01), clinical pregnancy/ET (OR = 1.73 [1.22, 2.45], p = 0.002), ongoing pregnancy/ET (OR = 1.99 [1.03, 3.83], p = 0.04), live birth rate/first cycle (OR = 1.59 [1.12, 2.24], p = 0.009) and per all embryo transfer (OR = 1.65 [1.06, 2.55], p = 0.03). No significant differences were found in embryo euploidy/number of biopsied blastocysts (OR = 1.34 [0.88, 2.04], p = 0.77), biochemical pregnancy/ET (OR = 1.23 [0.84, 1.80], p = 0.29), miscarriage rate/cycle (OR = 0.84 [0.54, 1.31], p = 0.35) and per pregnancy (OR = 0.71 [0.50, 1.02], p = 0.07), live birth rate/first embryo transfer (OR = 1.60 [0.80, 3.22], p = 0.18) and per concluded cycle (OR = 1.03 [0.53, 2.00], p = 0.92). To summarize, microfluidics may offer a beneficial approach in certain situations, particularly for patients with elevated sperm DNA fragmentation (SDF) levels. However, its integration into routine clinical practice cannot be justified yet in terms of cost-effectiveness. Additional research is needed to provide more comprehensive data on reproductive outcomes, especially live birth rates, which remain the ultimate goal of assisted reproductive technologies. Full article