The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
The digital transformation of reproductive health has been accelerated by rapid advances in Femtech, which offers new approaches to addressing infertility-related challenges. This review synthesizes the current evidence across three domains: consumer-facing technologies for fertility awareness and at-home diagnostics; the integration of digital health tools, including telehealth and mobile health (mHealth), into clinical management pathways; and the application of artificial intelligence (AI) in assisted reproductive technology (ART). Fertility tracking applications and home-based diagnostic tools may improve accessibility and support patient engagement in reproductive health management; however, evidence regarding their effects on clinically meaningful outcomes, including pregnancy and live birth rates, remains limited or inconsistent. Telehealth and mHealth platforms have been widely adopted and have demonstrated high patient satisfaction and feasibility, with clinical outcomes comparable to those of traditional in-person care in selected settings. In ART, AI-based approaches show promise for gamete and embryo assessment, selection, and outcome prediction, although the current evidence is derived largely from observational and validation studies and does not yet demonstrate consistent improvements in clinical outcomes. Despite these advances, important challenges remain, including variability in evidence quality, data privacy concerns, regulatory uncertainty, and disparities in digital access. Overall, although Femtech technologies have substantial potential to enhance reproductive care, their clinical integration should be guided by rigorous validation and cautious interpretation of the existing evidence.
Honduras has the highest rates of teen pregnancy and HIV in Central America, which are disproportionately concentrated in rural, low-income communities with high school dropout rates and limited access to sexual health education. This study evaluated the 'Taking Care of You' (TCY) program, a community-based educational intervention designed to improve reproductive health knowledge and social risk awareness among adolescents aged 11-18 years in rural northwest Honduras. We conducted a single-group, pre-post quasi-experimental study in El Rosario, Locomapa, Honduras. Eighty-seven adolescents were recruited through community leaders and school networks and participated in eight 3-h sessions from April to July 2024, covering sexual and reproductive health and social risk behaviours. A structured questionnaire with quantitative and qualitative components was administered pre- and post-intervention. McNemar tests, Wilcoxon signed-rank tests, and logistic regression models were used for quantitative analysis; descriptive-interpretive thematic analysis was applied to qualitative data. Before TCY, only 35.6% of participants knew about sexually transmitted infections (STIs), and fewer than half recognised risks of unprotected sex or substance use. Following TCY, there was increased knowledge on STIs, recognition of unprotected sex risks, self-assessed reproductive health knowledge, attitudes toward contraception, and comfort discussing sexual health and behaviours. Equitable gains were made across sex and age groups. Qualitative findings revealed shifts from stigma and avoidance toward openness and protective intentions. Knowledge and attitudinal gains were observed across sex and age groups; however, sustained behavioural change will require longer follow-up and continued structural support. Controlled trials with extended follow-up are needed to assess long-term behavioural impact.
To collate and appraise evidence from existing systematic reviews and meta-analyses on interventions to prevent stillbirth and reduce perinatal mortality across the reproductive continuum, including preconception, antenatal, intrapartum and immediate newborn periods. Umbrella review synthesising evidence from systematic reviews, including meta-analyses where available. A comprehensive search was conducted in CENTRAL (via Cochrane Register of Studies Online), PubMed, Embase and Web of Science, along with trial registries (WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and ISRCTN Registry), from inception to 12 January 2026. Systematic reviews and meta-analyses synthesising randomised controlled trials or quasi-experimental studies that reported stillbirth, perinatal mortality, fetal loss or fetal death were included. Reviews focused exclusively on predefined high-risk populations were excluded. Two reviewers independently extracted data and assessed methodological quality using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) certainty ratings were extracted as reported by the original review authors. Evidence synthesis followed a structured framework adapted from Ota et al, integrating direction of effect and certainty of evidence based on pooled estimates and GRADE assessments. Publication overlap was assessed using the Corrected Covered Area index where relevant. A total of 116 systematic reviews were included, synthesising evidence from randomised controlled and quasi-experimental studies across preconception, antenatal, intrapartum and immediate newborn periods. Evidence from individual reviews showed clear benefit for several interventions, including balanced energy-protein supplementation, home visits by community health workers, birth preparedness interventions, labour induction at or beyond 37 weeks of gestation and skilled or community-based intrapartum care, primarily for reducing perinatal mortality. Reduced antenatal visit schedules compared with standard care were associated with a possible increase in stillbirth or perinatal mortality, indicating potential harm. Many interventions-such as group antenatal care (ANC), nutritional education, case-note provision, routine ultrasound or Doppler monitoring, antibiotic treatment for bacterial vaginosis, antiretroviral therapy in pregnancy and several pharmacological or hormonal interventions-demonstrated unknown or inconclusive effects on stillbirth or perinatal mortality, largely due to imprecision and heterogeneity. This umbrella review identifies a range of interventions with evidence of effectiveness across the reproductive continuum, particularly those addressing maternal nutrition, continuity of ANC and quality intrapartum and newborn care. However, substantial evidence gaps remain, especially for interventions widely implemented without strong supporting evidence. These findings highlight the need for context-specific implementation research and prioritisation of proven strategies in low- and middle-income countries, where the burden of stillbirth remains highest. CRD42024531100.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen causing substantial economic losses to the global swine industry. The two genotypes, PRRSV-1 (European type) and PRRSV-2 (North American type), differ markedly in genetic characteristics and epidemiological patterns. The co-circulation and co-infection of these genotypes are increasingly reported. Concurrently, viral recombination events continue to shape PRRSV evolution. These scenarios collectively drive the need for rapid and accurate differential diagnostics. We aimed to establish and systematically optimize a dual-fluorescent enzymatic recombinase amplification (ERA) assay for simultaneous PRRSV-1 and PRRSV-2 identification. Highly conserved regions within the ORF7 gene of both genotypes were selected as targets, and genotype-specific primers and differentially labeled fluorescent probes were designed and screened. Reaction temperature, primer volume ratio, and probe volume ratio were optimized using an orthogonal experimental design, enabling efficient and synchronous dual-target amplification under isothermal conditions (42 °C). The developed assay exhibited high analytical specificity for PRRSV-1 and PRRSV-2. The limits of detection for PRRSV-1 and PRRSV-2 were 102 and 10 copies/μL, respectively. Clinical evaluation revealed an overall agreement rate of 98.78%. The developed dual-fluorescent ERA assay offered rapid reaction kinetics, simple operation, and high sensitivity and specificity. It enabled reliable differentiation of PRRSV-1 and PRRSV-2 without complex instrumentation, providing a practical and efficient tool for on-site diagnosis, epidemiological surveillance, and precise control of PRRS.
Yeast-derived nucleotides (YN) are gaining traction as high-value feed additives due to their proven multi-beneficial effects on the health and overall well-being of animals. Despite their proven efficacy, their specific impact on the reproductive performance of rabbit does remains poorly understood. This study investigates how dietary YN supplementation influences reproductive efficiency, hematological profiles, antioxidant status, blood health markers, and adipokine levels in rabbit does. A total of 120 nulliparous female rabbits were randomly assigned to four experimental groups (30 rabbit/group). The rabbits received either a basal diet (YN0, control) or supplemented with 0.25 (YN0.25), 0.5 (YN0.5), or 1 (YN1) g/kg of YN. Results showed that the YN-supplemented groups had significantly (P < 0.05) higher red blood cell (RBC) counts, platelet counts, total protein, and albumin levels compared to the control group. Dietary supplementation with YN led to a significant dose-dependent reduction in serum AST and ALT levels (P < 0.001). Similarly, concentrations of total lipids, creatine phosphokinase, haptoglobin, and lactate dehydrogenase (LDH) were significantly lower in all YN-treated groups compared to the control (P < 0.001). For cellular redox homeostasis, a significantly increased levels of TAC, CAT, GPx, and SOD, alongside a decrease in malondialdehyde (MDA) levels in rabbit fed diets with 0.25-1 g of YN (P < 0.05). A significant reduction (P < 0.05) was observed in serum inflammatory markers (toll-like receptor 4, and interleukin-4), the oxidative DNA damage marker 8-OHdG, and various circulating adipokines (leptin, adiponectin, visfatin, and irisin). In contrast, levels of immunoglobulins (IgM and IgG), interleukin-10 and reproductive hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (PG) showed significant (P < 0.05) improvement in rabbits from the YN groups. The conception rate increased significantly across all YN-supplemented diets (P < 0.05), reaching its peak in the YN1 and YN0.5 groups at 83.11%, compared to 70.66% in the control group. Both litter size at birth and litter size at weaning were greater in rabbit fed 0.5-1 g of YN (P < 0.05). The findings of this study suggest that dietary inclusion of YN (0.5-1 g/kg) enhances hematological markers, antioxidant defense mechanisms, and reproductive hormone profiles. These improvements in productive traits were accompanied by a notable reduction in inflammation and a modulation of adipokine levels, contributing substantially to the rabbit industry.
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder in which reproductive dysfunction coexists with insulin resistance, chronic low-grade inflammation, and heightened oxidative stress (OS). Increasing evidence indicates that these abnormalities are not independent phenomena but components of a self-perpetuating redox-endocrine network that sustains hyperandrogenism, anovulation, and metabolic impairment. This review critically synthesizes experimental, translational, and clinical data to examine whether vitamin D, myo-inositol, and melatonin, three widely used but often studied in isolation bioactives, can act synergistically as a mechanistically coherent 'bioactive cocktail' in PCOS. Vitamin D modulates inflammatory tone and steroidogenic signaling through vitamin D receptor-dependent transcription and immune-metabolic crosstalk; myo-inositol restores insulin signaling via inositolphosphoglycan second-messenger pathways, thereby attenuating hyperinsulinemia-driven androgen excess; and melatonin exerts pleiotropic effects on mitochondrial function, circadian regulation, and redox balance. Therefore, these agents converge on shared molecular hubs, including NF-κB, Nrf2, PI3K/Akt, and AMPK, linking OS reduction with endocrine and metabolic recalibration. The review further integrates emerging insights into gut microbiota-adipokineinteractions, highlighting how dysbiosis and altered adipokine profiles amplify oxidative and hormonal disturbances, and how these bioactives may counteract such system-level disruptions. While existing clinical trials report improvements in ovulatory function, insulin resistance indices, and OS biomarkers, outcomes remain heterogeneous due to differences in dosing, duration, and phenotype stratification. We propose a redox-guided, phenotype-aware framework for future trials, emphasizing biomarker-anchored outcomes and systems-level integration. If validated, combined vitamin D, myo-inositol, and melatonin supplementation may represent a precision nutraceutical strategy that targets the pathogenic core of PCOS rather than its isolated clinical manifestations.
This study compared the traditional blastocyst grading system with quantitative measurements of blastocyst expansion in relation to total pregnancy rate, implantation rate, and clinical pregnancy rate. A retrospective analysis was performed using data collected from patients undergoing frozen single embryo transfer cycles between 2021 and 2024. Single vitrified-warmed blastocyst transfers in self-patients were included, whereas cleavage-stage transfers and donor programs were excluded. All blastocysts were morphologically graded using the Gardner grading system. The degree of expansion was assessed morphometrically by measuring the inner diameter of the blastocyst from images obtained at the equatorial plane during embryo transfer, using Hamilton Thorne laser software. Multiple statistical tests were applied to analyze both qualitative and quantitative assessments of blastocysts in relation to clinical outcomes. When comparing morphological parameters such as the quality of inner cell mass (ICM), trophectoderm (TE), and blastocyst expansion level, ICM and TE quality were found to significantly influence clinical outcomes. In comparing qualitative and quantitative (mean diameter) assessments of blastocysts with clinical outcomes, TE grade and blastocyst expansion level assessed qualitatively showed significant effects, whereas ICM quality and quantitative expansion measurements did not demonstrate statistical significance. Qualitative assessments of TE grade and blastocyst expansion level appear to be stronger predictors of clinical outcomes than ICM grade and morphometric assessment of blastocyst expansion. Larger datasets, including morphometric evaluation of ICM and TE cells, are recommended to clarify the predictive value of morphometric parameters.
Polystyrene exposure poses an increasing threat to reproductive health, and effective interventions remain limited. Jinkui Shenqi pills (JSP), a traditional Chinese medicine used to treat reproductive disorders, may protect against such damage. This study integrated network pharmacology with experimental validation to explore the mechanisms by which JSP counteracts polystyrene-induced reproductive toxicity. Potential targets related to polystyrene toxicity and bioactive components of JSP were retrieved from relevant databases. Overlapping targets were identified using VENNY 2.1. Protein-protein interaction networks were constructed using STRING, and core targets were identified with Cytoscape. Enrichment analyses were performed using DAVID. Molecular docking was used to evaluate ligand-target binding. A polystyrene-exposed mouse model was established, and tissue injury and recovery were assessed by hematoxylin-eosin (HE) staining and Western blotting (WB). In-depth screening identified 111 overlapping targets, and three key molecules-AKT serine/threonine kinase 1 (AKT1), caspase-3 (CASP3), and B-cell lymphoma 2 (BCL2)-were selected for further investigation. Gene Ontology analysis highlighted phosphorylation-related processes and responses to xenobiotics, while Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment in pathways related to lipid metabolism, atherosclerosis, cancer, and phosphatidylinositol-3-kinase (PI3K)-AKT signaling. Molecular docking confirmed effective binding of sitosterol, alisol B monoacetate, acetate, and alisol to these targets. HE staining revealed polystyrene-induced damage in testicular and ovarian tissues, which was effectively alleviated by JSP administration. WB results further demonstrated that JSP upregulated the expression of core target proteins, supporting its protective role against polystyrene-induced reproductive toxicity. JSP mitigates polystyrene-induced reproductive toxicity by modulating AKT1, CASP3, and BCL2, supporting its potential as a protective agent.
Anabolic-androgenic steroids such as boldenone (BOL) are used in veterinary medicine to improve growth, food conversion in food-producing animals, and recently utilized by bodybuilders to increase muscle mass and enhance physical performance. Additionally, they have serious adverse effects on various organs, mostly the testicular tissues. In this context, the purpose of this study was to assess BOL-induced testicular damage and the potential protective benefits of cerium oxide nanoparticles (CeNP). Twenty-four adult male rats were randomly allocated into 4 equal groups: Control, BOL (5 mg/kg), CeNP (100 μg/kg), and a combination of BOL and CeNP-treated groups. All of the treatments were administered intraperitoneally to the rats, twice a week for 8 consecutive weeks. Hematological parameters, oxidative stress markers, pro-inflammatory cytokines, and hormonal profiles were measured using standard biochemical and immunoassay techniques, as well as histopathological changes in the testicular tissue. The results showed that BOL markedly increased testicular oxidative damage as demonstrated by a drastic elevation of lipid peroxidation marker (MDA), NO levels, with a notable decline in GSH concentration, as well as SOD and CAT enzyme activity. Additionally, inflammation has also been elicited, evidenced by elevated levels of testicular proinflammatory cytokines, including TNF-α and IL-6, along with a marked decrease in serum levels of LH, FSH, and testosterone. Interestingly, CeNP diminished the detrimental effects of BOL on testicular tissue by reducing lipid peroxidation, inflammation, and enhancing antioxidant activity. The present findings indicated that CeNP may serve as a promising protective agent against BOL-induced reproductive damage in male rats.
Nicotinamide mononucleotide (NMN), a key precursor of nicotinamide adenine dinucleotide (NAD+), has recently emerged as a promising therapeutic candidate for age-related diseases. This review critically evaluates preclinical evidence regarding the effects of NMN on ovarian health, with particular emphasis on its potential to attenuate ovarian aging, improve follicular reserve, and restore endocrine function. Animal studies have demonstrated that NMN supplementation enhances mitochondrial function, reduces oxidative stress, and modulates sirtuin activity in ovarian tissue. These effects contributed to improved oocyte quality, delayed ovarian senescence, and prolonged reproductive lifespan. In models of chemotherapy-induced ovarian insufficiency and age-related ovarian decline, NMN administration was associated with increased folliculogenesis and normalization of hormonal profiles. Furthermore, the anti-inflammatory and anti-apoptotic properties of NMN suggest potential therapeutic applications in conditions such as premature ovarian insufficiency and polycystic ovary syndrome. Despite encouraging findings in rodent models, clinical translation remains limited. This review summarizes the key molecular pathways influenced by NMN, including the NAD+/sirtuin-1 (SIRT1) axis, and highlights important gaps in current knowledge. Collectively, the available evidence underscores the therapeutic potential of NMN while emphasizing the need for well-designed human studies to establish its efficacy and safety in reproductive medicine.
Cisplatin-induced cardiotoxicity is a major global health challenge among patients on platinum-based chemotherapy and it has limited the clinical use of this drug despite its effectiveness Cisplatin. It exerts its cardiotoxicity via the downregulation of Nrf2/HO-1 and glutathione system, while L-arginine, a semi-essential amino acid and an anti-oxidant, activates Nrf2/HO-1 and enhances glutathione antioxidants. However, data on the effect of L-arginine on cisplatin-induced cardiotoxicity is scarce. Therefore, this study examined the effect of L-arginine on cisplatin-induced cardiotoxicity. Also, the involvement of the Nrf2/HO-1 pathway and glutathione system was explored. Twenty-four male Wistar rats were randomly allotted into 4 groups after a 2-week acclimatization period; control, arginine-treated, cisplatin-treated, and cisplatin+arginine-treated. L-arginine blunted cisplatin-induced decrease in body and cardiac weight, and cardiac/tibial length ratio. Also, L-arginine attenuated cisplatin-induced rise in cardiac lactate dehydrogenase and creatinine kinase activities and lactate and troponin levels. More so, L-arginine attenuated cisplatin-induced rise in the circulating levels of glucose, total cholesterol, and triglyceride, as well as atherogenic indices and insulin resistance. Furthermore, L-arginine improved cisplatin-induced alteration in cardiac histoarchitecture. These findings were associated with L-arginine-led suppression of cisplatin-induced rise in cardiac MDA, IL-1β, TNF-α, NF-kB, and myeloperoxidase activity, and cisplatin-induced reductions in cardiac GPx, GST, SOD, catalase, and HO-1 activities, and Nrf2 expression. L-arginine attenuated cisplatin-induced cardiotoxicity and defective cardiac metabolic flexibility by activating Nrf2/HO-1 signaling and upregulating glutathione.
Early-onset oral squamous cell carcinoma (EO-OSCC), commonly defined as occurring in individuals under 50 years of age, is increasingly recognized as a potentially distinct clinical subset with differences in exposure patterns and tumor biology compared with conventional oral squamous cell carcinoma (OSCC). Unlike typical OSCC, which is strongly associated with tobacco and alcohol, EO-OSCC more frequently affects never-smokers/never-drinkers, posing challenges for early recognition, risk stratification, and management. This review integrates evidence mapping with narrative synthesis to summarize current knowledge on EO-OSCC, focusing on epidemiology, emerging risk factors, molecular alterations, tumor microenvironment characteristics, and clinical implications. Literature was searched across PubMed, Scopus, Embase, Web of Science, and the Cochrane Library up to August 2025, complemented by global cancer databases (GLOBOCAN/Cancer Tomorrow) and international trial registries. Available data suggest distinct biological features, including relatively low tumor mutational burden, recurrent alterations in CDKN2A, TP53, NOTCH1, and EGFR, epigenetic dysregulation, and a checkpoint-dominant immunosuppressive tumor microenvironment. Alongside traditional carcinogens, modifiable determinants such as sugar-sweetened beverages, electronic cigarette use, and oral microbial dysbiosis have emerged as plausible contributors, although evidence remains heterogeneous. Despite frequently aggressive histopathologic features, younger patients may tolerate intensive multimodal therapies better and achieve favorable outcomes. These findings highlight the urgent need for age-specific prognostic tools, biomarker-guided therapies, and early detection protocols. International collaboration will be key to improving survival and long-term quality of life in this growing patient population.
Nandrolone, a synthetic anabolic steroid, is frequently used for muscle enhancement but is known to compromise male fertility, particularly when administered at supraphysiological doses. Conversely, royal jelly exhibits antioxidant activity and may exert protective effects on reproductive function. This study aimed to assess the histomorphological effects of nandrolone, royal jelly, and their concurrent administration on testicular architecture during pubertal development. Thirty-five male Syrian mice (4-5 weeks old, approximately 25 g) were randomly assigned to five groups (n=7): untreated control, sesame oil vehicle, nandrolone (10 mg/kg/week), royal jelly (500 mg/kg/day), and combined nandrolone plus royal jelly. On day 32, animals were euthanized, and testicular tissues were harvested for morphological and histological evaluation. Paraffin-embedded sections were stained with hematoxylin and eosin, and seminiferous tubule diameters were quantitatively assessed. Nandrolone administration increased testicular weight and the gonadosomatic index relative to controls. Royal jelly similarly enhanced testicular metrics. However, co-treatment markedly reduced testicular weight, gonadosomatic index, and lumen diameter, while germinal epithelium thickness was increased. Nandrolone alone may not impair fertility during pubertal maturation, and royal jelly may enhance reproductive potential when administered prepubertally. Nonetheless, their combined administration appears to disrupt spermatogenic architecture, potentially impeding sperm transit through epithelial hyperplasia and delaying testicular maturation.
Endocrine-disrupting chemicals (EDCs) are widespread environmental contaminants that interfere with hormonal signaling and are associated with adverse reproductive, metabolic, thyroid, neurodevelopmental, and other endocrine-related health outcomes. Diet, consumer products, and indoor environments are major sources of exposure. While regulatory approaches are critical, practical interventions to reduce exposure and mitigate health effects are increasingly being explored. This narrative review synthesizes evidence on interventions that reduce human exposure to EDCs. This review examines if these reductions lead to noticeable health improvements, focusing especially on whether the effects linked to EDCs can be reversed. Human intervention and observational studies assessing dietary, behavioral, residential, and biochemical strategies to reduce internal EDC biomarkers were reviewed. Dietary interventions, such as reducing consumption of packaged and canned foods, increasing intake of fresh or organic products, and adopting safer food storage practices, consistently lowered urinary levels of bisphenol A (BPA) and phthalates. Behavioral interventions, including substituting personal care products and avoiding high-exposure consumer products, produced rapid reductions in internal EDC concentrations. Residential interventions targeting indoor air and dust showed promising but limited evidence. Biochemical interventions, including nutritional and metabolic modulation, may mitigate the biological effects of exposure. Finally, emerging data suggest that metabolic dysfunction, lipid abnormalities, and functional reproductive outcomes may be partially reversible. In contrast, cancer and developmental effects from early-life exposure appear less amenable to reversal. Lifestyle, environmental, and biochemical interventions can meaningfully reduce internal EDC biomarkers; however, evidence linking these reductions to clinically meaningful health outcomes remains limited and inconclusive. These approaches represent actionable complements to regulatory efforts, though long-term benefits require further study.
This study examined the potential protective role of date palm fruit extract (DPFE) and its underlying mechanisms against busulfan-induced sperm damage and infertility. Sixty male Wistar rats were allocated to control, busulfan alone (10 mg/kg), DPFE alone (4 mg/kg), and busulfan+DPFE co-treatment groups for a period of 56 days. Semen parameters were evaluated along with DNA fragmentation, assessed using the sperm chromatin dispersion test, and protamine deficiency, detected by chromomycin A3 staining. Testicular oxidative stress was assessed by measuring malondialdehyde (MDA) levels as well as superoxide dismutase (SOD) and catalase (CAT) activities. Phytochemical analysis confirmed the high polyphenolic and flavonoid content of DPFE. Busulfan significantly induced testicular oxidative stress, as evidenced by increased MDA levels and reduced SOD and CAT activities. These alterations were accompanied by significant declines in sperm motility and viability, deterioration of sperm morphology, and marked increases in protamine deficiency and DNA fragmentation. Co-administration of DPFE significantly counteracted these adverse effects by normalizing testicular oxidative status, reflected by decreased MDA levels and restoration of SOD and CAT activities. Consequently, DPFE improved sperm motility and morphology and, importantly, reduced the proportion of sperm exhibiting high DNA fragmentation and protamine deficiency. Antioxidant-rich DPFE exerts a significant protective effect against busulfan-induced testicular toxicity, with its mechanism strongly linked to attenuation of testicular oxidative injury, thereby improving conventional sperm quality and, critically, preserving sperm chromatin structure and DNA integrity.
The family with sequence similarity (FAM) gene family links pathological mechanisms of male infertility and oncogenesis. This review focuses on five key FAM members (FAM71D, FAM46C, FAM170A, FAM83D, and FAM172A), which were selected based on: clinical relevance (FAM83D as a breast cancer prognostic biomarker, hazard ratio, 1.29, p<0.05; FAM71D homozygous mutation c.440G>A associated with asthenoteratospermia); adequate experimental validation (in vitro assays, in vivo models, and clinical samples-for example, FAM170A knockout mice exhibit male infertility, with reduced transcription observed in patients); and recent impact (≥30 PubMed-indexed studies within 5 years and clearly defined mechanisms). In reproduction, FAM71D maintains sperm motility via calmodulin- plasma membrane Ca2+-ATPase (PMCA)- Ca2+ signaling, FAM46C anchors the sperm head-flagellum junction, and FAM170A regulates chromatin remodeling through ubiquitin- specific protease 7 (USP7)-mediated H2B deubiquitination. In oncology, FAM83D activates mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling to drive hepatocellular carcinoma, whereas FAM172A dysregulates p38 mitogen-activated protein kinase in thyroid cancer. Translational advances include FAM83B nanodetection, the Fam20C inhibitor FL-1607 (IC50=2.1 μM), and clustered regularly interspaced short palindromic repeats (CRISPR)-corrected FAM170A. Cross-species functional divergence remains a challenge. FAM genes enable novel diagnostics and targeted therapies for reproductive and oncological care, with near-term clinical applications in personalized assisted reproductive technology and cancer precision medicine.
This study assesses the frequency and severity of ultrasound-detected testicular alterations across age groups (young and adult) in 219 bucks. Sperm quality and testicular echotexture were evaluated, and their associations with reproductive pathogens (Coxiella (C.) burnetii, caprine arthritis encephalitis virus (CAEV), Chlamydia (C.) abortus and Mycoplasma (M.) agalactiae) were analyzed. Additionally, qPCR was also performed on ejaculates from seropositive bucks. Seminal microbiota was characterized in three groups: 1 (seronegative without lithiasis), 2 (seropositive with lithiasis), and 3 (qPCR-CAEV-positive). A 68.5% of bucks showed testicular microlithiasis (50.2% bilateral and 18.2% unilateral). Moreover, frequency of bilateral lesions differed according to age, being higher in adults, who also showed larger microlithiasis area (P < 0.05). Age was negatively correlated with sperm concentration (P < 0.05). Seropositivity was 35.8% for C. burnetii and 58.8% for CAEV. Adults showed higher CAEV seropositivity (P < 0.001), and 4.2% of ejaculates tested qPCR positive for this pathogen. Bacterial richness was greater (P < 0.001) in group 2 than in group 1. Firmicutes dominated groups 1 and 2, whereas Fusobacteriota prevailed in group 3. The most frequent genus in all three experimental groups was Oceanivirga, with higher abundance in group 1 than in group 2 (P < 0.05). These findings suggest that ejaculate microbiota may be influenced by ultrasound abnormalities and exposure to CAEV and C. burnetii, supporting the use of testicular ultrasound to detect bucks prone to reproductive problems and associated health risks, while also highlighting the need to include males in CAE and Q fever control programs.
This study compared serum anti-Müllerian hormone (AMH) concentrations measured in capillary fingerstick and venous samples using the automated fluorescence immunoassay system (AFIAS) AMH assay and evaluated procedure-related discomfort. We conducted a prospective paired-sample method-comparison study at Korea University Anam Hospital, Seoul, Republic of Korea, in October 2023. During a single clinic visit, paired venous and fingerstick blood samples were obtained from each participant. Serum AMH concentrations were measured with the AFIAS AMH assay, and all laboratory analyses were performed at EONE Laboratories, Incheon, Republic of Korea. Agreement between sampling methods was evaluated using Passing-Bablok regression, Bland-Altman analysis, Pearson and Spearman correlation coefficients, and the intraclass correlation coefficient (ICC). Procedure-related pain was assessed immediately after sampling using an 11-point numeric rating scale (NRS; 0=no pain, 10=worst pain imaginable). Overall, 90 women aged 25-46 years provided paired samples. Mean AMH concentrations were 2.74 ng/mL (range, 0.11 to 9.99) in venous samples and 3.42 ng/mL (range, 0.17 to 11.55) in fingerstick samples. Passing-Bablok regression indicated proportional bias (y=0.123+1.175x), with no significant deviation from linearity on the cumulative sum (CUSUM) test (p=0.07). Agreement and correlation were high (ICC=0.930; Pearson r=0.982; p<0.001). Mean NRS pain scores were 2.36 for venipuncture and 2.91 for fingerstick sampling. Capillary fingerstick sampling may be an alternative approach for AMH measurement when improved access to testing is desired. However, because proportional bias was observed, fingerstick and venous AMH measurements should not yet be considered fully interchangeable without further validation.
Caesarean section (CS) rates have increased worldwide, raising concerns about maternal and child health and healthcare costs. Although vaginal birth after caesarean (VBAC) is considered a safe alternative, its use remains limited and variable. We aimed to identify sociodemographic, clinical, and organizational factors associated with VBAC utilization in Tuscany, Italy, and to assess the impact of VBAC on perinatal outcomes. We conducted a retrospective population-based study using administrative healthcare data (2021-2024), including women with one previous CS who delivered at term (n = 6,737). Single-level and multi-level logistic regression models were used to investigate independent determinants of VBAC utilization and its association with perinatal outcomes. Missing data were handled using multiple imputation. Overall, 27% of women underwent VBAC. Older maternal age, unemployment, Italian nationality, assisted reproductive technologies, diabetes, private care pathways, and indicators of more intensive prenatal surveillance were associated with lower odds of VBAC, whereas antenatal class attendance and early initiation of prenatal care were associated with higher odds. VBAC rates increased from 2021 to 2022 to 2023-2024. The multi-level model showed that 25.4% of the variance in VBAC utilization was attributable to differences between hospitals. VBAC was associated with improved perinatal outcomes (higher Apgar scores; increased breastfeeding and skin-to-skin contact; lower neonatal ventilation) and reduced length of stay and hospitalization costs. VBAC utilization in Tuscany remains below recommended levels. Hospital-level differences explain a substantial proportion of the observed variation, supporting the need to standardize VBAC practices at the regional level.