Search Results (285)

Fatty acid amide hydrolase (FAAH) is a central component of the endocannabinoid system (ECS), where it primarily regulates intracellular levels of anandamide (AEA) through enzymatic hydrolysis. Although FAAH has been extensively studied in neural and immune contexts, its involvement in female reproductive physiology is receiving increasing attention. Accumulating evidence indicates that FAAH participates in several important ovarian processes, including follicular development, steroid hormone synthesis, ovulation, and luteal function. In this review, we outline the biochemical properties of FAAH and its spatial distribution in ovarian tissues, with a particular focus on how FAAH-mediated AEA metabolism contributes to intraovarian signaling. Furthermore, we highlight the potential implications of altered FAAH activity in ovarian disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and infertility. By integrating molecular observations with clinical findings, this work provides updated perspectives on FAAH as both a physiological regulator and a potential therapeutic target in reproductive medicine. Full article

This systematic review aimed to summarize the effects of astaxanthin (ASX) supplementation on oxidative stress, inflammation, and metabolic regulation in human studies. A systematic search was conducted in Scopus, Web of Science (WOS), and PubMed for articles published between 2020 and 2025. Fifteen studies involving human participants were included, while in vitro and animal studies were excluded. ASX consistently reduced pro-inflammatory cytokines (IL-6, TNF-α, TGF-β1) and oxidative stress indices while increasing antioxidant capacity (SOD, TAC). Combined ASX and exercise interventions improved body composition, lipid profiles, insulin sensitivity, and immune recovery. In women with Polycystic Ovary Syndrome (PCOS) or endometriosis, ASX downregulated endoplasmic reticulum stress–related apoptotic pathways and improved oocyte and embryo quality. Cardiometabolic and respiratory outcomes showed improved endothelial function and reduced disease severity. Astaxanthin demonstrates broad antioxidant and anti-inflammatory properties, supporting its role as a promising adjunctive therapy for metabolic, reproductive, and cardiovascular health. Further well-designed clinical trials are needed to confirm optimal dosing and mechanisms of action. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine–metabolic disorder in which skeletal muscle insulin resistance contributes substantially to cardiometabolic risk. Pioglitazone improves insulin sensitivity in women with PCOS, yet the underlying transcriptional changes and their potential as treatment-response biomarkers remain incompletely defined. We aimed to reanalyse skeletal muscle gene expression from pioglitazone-treated PCOS patients using modern machine learning and network approaches to identify candidate biomarkers and regulatory hubs that may support precision therapy. Methods: Public microarray data (GSE8157) from skeletal muscle of obese women with PCOS and healthy controls were reprocessed. Differentially expressed genes (DEGs) were identified and submitted to Ingenuity Pathway Analysis to infer canonical pathways, upstream regulators, and disease functions. Four supervised machine learning algorithms (logistic regression, random forest, support vector machines, and gradient boosting) were trained using multi-step feature selection and 3-fold stratified cross-validation to provide superior Exploratory Gene Analysis. Gene co-expression networks were constructed from the most informative genes to characterize network topology and hub genes. A simulated multi-omics framework combined selected transcripts with representative clinical variables to explore the potential of integrated signatures. Results: We identified 1459 DEGs in PCOS skeletal muscle following pioglitazone, highlighting immune and fibrotic signalling, interferon and epigenetic regulators (including IFNB1 and DNMT3A), and pathways linked to mitochondrial function and extracellular matrix remodelling. Within this dataset, all four machine learning models showed excellent cross-validated discrimination between PCOS and controls, based on a compact gene panel. Random forest feature importance scoring and network centrality consistently prioritized ITK, WT1, BRD1-linked loci and several long non-coding RNAs as key nodes in the co-expression network. Simulated integration of these transcripts with clinical features further stabilized discovery performance, supporting the feasibility of multi-omics biomarker signatures. Conclusions: Reanalysis of skeletal muscle transcriptomes from pioglitazone-treated women with PCOS using integrative machine learning and network methods revealed a focused set of candidate genes and regulatory hubs that robustly separate PCOS from controls in this dataset. These findings generate testable hypotheses about the immunometabolism and epigenetic mechanisms of pioglitazone action and nominate ITK, WT1, BRD1-associated loci and related network genes as promising biomarkers for future validation in larger, independent PCOS cohorts. Full article

Vitamin D is well established for its skeletal effects, being a cornerstone of several endocrine disorders. In recent years, it has come under investigation as a potential disease-modifying drug in several endocrine disorders through its immune modulatory and anti-tumorigenic action, particularly in thyroid disease, gynecologic disorders, and general fertility. Vitamin D supplementation is well established in the treatment of osteoporosis, osteomalacia, hypoparathyroidism, and primary hyperparathyroidism. In autoimmune thyroid disease, there is a negative correlation between 25(OH)D3 levels and prevalence. Currently available data are inconclusive on supplementation as a disease-modifying treatment. In Hashimoto’s thyroiditis, while some found improved thyroid function, a decline in progression, and antibody titers, these findings were not consistent, and some found no improvements. Painless postpartum thyroiditis severely lacks evidence. Interventional studies failed to demonstrate benefits in Graves’ disease. The literature consistently reports lower vitamin D levels in infertility, polycystic ovarian syndrome (PCOS), and endometriosis. In PCOS, data suggest that vitamin D supplementation is beneficial; however, results in exact benefits vary and there is no consensus on dosing. Current guidelines support supplementation as part of preconception nutritional care. In general, for female infertility and endometriosis, the results are conflicting, with a lack of high-quality evidence. The literature suggests there is a possible benefit regarding sperm motility, but not in testosterone levels for males. In conclusion, while in vitro studies and animal models are promising, the available evidence is often contradictory, with high heterogeneity in study designs and populations. Our paper highlights the need for further high-quality research to resolve current controversies. Full article

Background/Objectives: A decrease in serum AMH is generally associated with low ovarian response in assisted reproductive procedures, whether or not in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is performed. Methods: We report a case involving a 31-year-old woman who had never been pregnant and with irregular menstrual cycles. An ultrasound scan performed on the second day of the cycle showed several annular follicles, a high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio suggesting polycystic ovary syndrome (PCOS), and an undetectable serum level of AMH. Results: Despite these observations, she exhibited an unpredictable hyperresponse during controlled ovarian stimulation, followed by a failed pregnancy despite successful in vitro fertilization with ICSI and a good-quality thawed embryo transfer (4AA). Conclusions: This case highlights the challenges of relying solely on AMH as a predictive marker of ovarian response. Although AMH is widely used for assessing ovarian reserve and stimulation outcomes, its limitations become evident in atypical cases. The paradoxical hyperresponse observed here may result from alternative regulatory mechanisms influenced by elevated LH levels, enhanced gonadotropin receptor sensitivity, or local ovarian factors. This report underscores the need for a personalized, multidimensional approach combining hormonal profiles, ultrasound assessments, and clinical history to optimize stimulation protocols and mitigate risks such as ovarian hyperstimulation syndrome (OHSS). Such tailored protocols are essential for managing patients with complex profiles, particularly those with undetectable AMH levels. Further research is needed to explore the mechanisms behind these atypical ovarian responses, including the roles of genetic polymorphisms, inflammatory markers, and environmental factors. This case demonstrates the importance of cautious interpretation of AMH results and emphasizes the value of comprehensive evaluations in assisted reproductive technologies. Full article

Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery calcium, CAC), (2) patients with established atherosclerotic plaques, and (3) individuals with AS risk factors. Methods: The systematic search was conducted in the PubMed database according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were as follows: (i) publication date between 2009 and 2024; (ii) identification of potential biomarkers for AS in subjects with a diagnosis of AS or with one or more traits characteristic of the disease (i.e., CAC or IMT); (iii) identification of potential AS biomarkers in subjects with atherogenic clinical conditions (i.e., Down’s syndrome, DS, polycystic ovarian syndrome, PCOS, and systemic lupus erythematosus, SLE); (iv) metabolomic studies; and (iv) studies in human samples. Exclusion criteria comprised the following: (i) studies on lipid metabolic diseases unrelated to AS, (ii) “omics” results not derived from metabolomics, (iii) reviews and studies in animal models or cell cultures, and (iv) systematic reviews and meta-analyses. Of 90 eligible studies screened, 24 met the inclusion criteria. Results: Across subclinical and overt AS, consistent disturbances were observed in amino acid, lipid, and carbohydrate metabolism. Altered profiles included branched-chain amino acids (BCAAs), aromatic amino acids (AACs) and derivatives (e.g., kynurenine–tryptophan pathway), bile acids (BAs), androgenic steroids, short-chain fatty acids (FAs)/ketone intermediates (e.g., acetate, 3-hydroxybutyrate, 3-HB), and Krebs cycle intermediates (e.g., citrate). Several metabolites (e.g., glutamine, lactate, 3-HB, phosphatidylcholines, PCs/lysophosphatidylcholines, lyso-PCs) showed reproducible associations with vascular phenotypes (IMT/CAC) and/or clinical AS. Conclusions: The identification of low-weight metabolites altered in both subclinical and overt AS suggests their potential as candidate biomarkers for early AS diagnosis. Given the steady increase in deaths from cardiovascular disease, a manifestation of advanced AS, this finding could have significant clinical relevance. Full article

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by reproductive abnormalities such as hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently accompanied by metabolic disturbances such as insulin resistance, obesity and dyslipidemia. Genome-wide association studies (GWASs) have identified several susceptibility loci, yet little is known about their functional implications. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) has emerged as a powerful gene editing tool in bridging this gap by allowing researchers to directly target candidate genes in ovarian and metabolic pathways. For instance, experimental models have highlighted the role of CYP17A1 and DENND1A.V2 in androgen excess, anti-Müllerian hormone (AMH) in follicular arrest, and insulin receptor substrate 1 (IRS1) and PPARγ in insulin signaling and adipogenesis. To highlight the multifactorial nature of PCOS, animal models, including zebrafish and rodents, have been used to reveal interactions between reproductive and metabolic phenotypes. Nevertheless, most studies remain restricted to single-gene models, and dual-gene models or combined gene editing and hormonal induction models remain underexplored. Future research integrating precision editing, multi-omic platforms, and patient-derived organoids may provide more accurate disease models and novel therapeutic strategies. Full article

Fungal endophytes can be identified in a wide range of plant species which help to protect from both abiotic and biotic stressors. This research focused on using high-throughput sequencing (HTS) analysis to gain insight into the foliar endophytic fungal diversity between Morinda tinctoria and Pithecellobium dulce. The study obtained a total of 118,547 sequencing reads, which were grouped into 266 Operational Taxonomic Units (OTUs) with a 97% similarity threshold. M. tinctoria had more OTUs than P. dulce. Alpha diversity results show that both plant species support varied microbial communities with similar but distinct biodiversity profiles. The Shannon index revealed that M. tinctoria had considerably more fungal diversity than P. dulce. The correlation matrix and PCoA depicts the pairwise correlations between several soil metrics such as the total nitrogen level, entire phosphorus, overall potassium, and the electrical conductivity, total carbon from organic matter, pH levels, manganese, iron, zinc, copper, and boron. The OTUs were classified into 5 phyla, 18 classes, 40 orders, 70 families, and 36 genera, where the phylum Ascomycota has a relative abundance of (50–55%), followed by Basidiomycota at (55–60%). The most abundant genera were Wallemia (30–35%), Saitozyma (30–40%), and Talaromyces (20–25%), with average relative abundances. Unassigned genera show a significant proportion of fungal taxa that are still taxonomically unclear. A comparative analysis has been performed between the two plants, M. tinctoria has a higher fungal diversity, which is frequently associated with increased ecological stability, disease resistance, and better functional relationships with the host plant. Full article

Human infertility represents a multifaceted condition, with oxidative stress (OS) and microRNAs (miRNAs) emerging as key contributors to its pathophysiology. This comprehensive review explores the complex interplay between reactive oxygen species (ROS) and miRNAs in male and female reproductive dysfunctions. ROS overproduction damages DNA, lipids, and proteins, impairing sperm quality and oocyte maturation. In males, OS is a leading cause of infertility, especially in conditions like varicocele, where key miRNAs such as miR-21, miR-34a, and miR-155 are dysregulated. In females, oxidative imbalance affects granulosa cells and follicular environments in disorders such as PCOS, premature ovarian insufficiency (POI), and endometriosis. Several miRNAs (e.g., miR-132-3p, let-7, miR-642a-5p) regulate mitochondrial function, steroidogenesis, and apoptosis through redox-sensitive signaling pathways (PI3K/Akt, NF-κB, FOXO1). Their altered expression in ovarian and seminal environments correlates with poor reproductive outcomes. Emerging evidence supports their potential role as diagnostic biomarkers and therapeutic targets, although most findings are based on animal models or in vitro studies. This review highlights the therapeutic potential of miRNA modulation and calls for further clinical research to validate miRNA-based interventions. Ultimately, understanding the miRNA–OS nexus offers promising avenues for improving diagnosis, prognosis, and treatment of infertility across both sexes. Full article

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder affecting 6–20% of women of reproductive age, manifesting through hyperandrogenism, ovulatory dysfunction, insulin resistance, and diverse metabolic derangements. Increasing evidence highlights the contribution of environmental factors, particularly endocrine-disrupting chemicals (EDCs), to PCOS susceptibility and severity. Sunscreen ultraviolet (UV) filters such as oxybenzone (benzophenone-3) and octinoxate (ethylhexyl methoxycinnamate) are widely used EDCs with established systemic absorption and biomonitoring evidence in human populations. Their endocrine-disrupting potential encompasses estrogenic and anti-androgenic activity, interference with steroidogenic enzymes, modulation of thyroid hormone, induction of oxidative stress, and epigenetic reprogramming, all of which are mechanistic pathways that overlap with PCOS pathophysiology. This evidence-based study critically appraises the evidence linking oxybenzone and octinoxate exposures to ovarian endocrinology, with a PCOS-specific focus. Human exposure patterns, pharmacokinetics, and regulatory perspectives are summarized alongside preclinical and in vitro data implicating these filters in ovarian dysfunction. Mechanistic intersections with PCOS include hyperandrogenism, disrupted folliculogenesis, oxidative stress-adipokine imbalance, and potential impairment of vitamin D signaling. Although epidemiological studies directly addressing PCOS outcomes remain sparse, the convergence of toxicological evidence with known endocrine vulnerabilities in PCOS underscores a need for targeted investigation. By mapping exposure pathways and mechanistic disruptions, this appraisal emphasizes the translational relevance of UV filter toxicity in the context of PCOS. It advocates for PCOS-specific biomonitoring cohorts, mechanistic studies, and regulatory consideration of reproductive endpoints while balancing the dermatological benefits of photoprotection against reproductive risks. Full article

Forest fires are key disturbance factors in forest ecosystems, and soil fungi play an irreplaceable role in post-fire recovery. This study focused on forest areas burned in 2000 in the Daxing’anling region of China, targeting long-term recovery sites with different fire intensities. Illumina MiSeq sequencing was used to analyze the structural characteristics of fungal communities and their environmental drivers. Results showed that compared with the control check (CK), the Shannon index of the low fire group (L) increased significantly (p < 0.05), while moderate (M) and high (H) fire groups reduced fungal diversity significantly. PCoA indicated significant differences in community structure (R² = 0.97, p = 0.001). In highly burned areas, the relative abundance of Ascomycota reached 94.17%, and Basidiomycota lost its dominance. Spearman analysis showed that pH, available phosphorus, available potassium, soil fluorescein diacetate hydrolase, soil dehydrogenase, and soil urease were significantly positively correlated with fungal alpha diversity. RDA revealed that total nitrogen, available phosphorus, soil water content, alkaline nitrogen, active potassium, and dissolved organic carbon had extremely significant effects on soil fungal community composition (p < 0.01). Co-occurrence network analysis indicated that symbiotic relationships dominated all groups. Networks in L and M groups were more complex, while that in H group was simplified and severely damaged. This study indicated that after long-term recovery, soil fungal communities in low fire areas returned to pre-fire levels; those in moderate and high fire areas did not recover, with high fire burns causing severe damage and community structure reorganization. Full article

Rhizoctonia solani (Rs) and Sclerotinia sclerotiorum (Ss) are devastating pathogens of rice and rapeseed, contributing 20–69% and 10–50% of yield losses, respectively. These pathogens develop resistant overwintering and/or oversummering sclerotia, which serve as inocula for infection in the subsequent season under favorable conditions. The present study was designed to investigate the month-wise variation in microbial diversity by mixing Rs and Ss sclerotia separately in rice-rapeseed rotation field soil, thereby identifying key microbial players associated with specific sclerotia and their implications for subsequent crops. Therefore, we incubated 2.5 g of Rs and Ss sclerotia in 100 g of soil for 3 months to mimic the field conditions and subjected month-wise soil samples to 16S rRNA and ITS2 sequencing. Data analysis of bacterial communities revealed diversity, richness, and evenness in Ss treated soil samples compared to the control, while fungal communities exhibited less diversity. These results were also evident in PCoA and hierarchical clustering, where control and treated samples were scattered in 16S rRNA and ITS sequencing. Genus level diversity exhibited enrichment of bacterial genera with known beneficial potential, notably Acidibacter, Stenotrophobacter, Sphingomonas, Flavisolibacter, Gaiella, and Neobacillus in control. Beneficial bacterial genera such as Ramlibacter, Geomonas, Kofleria, Nitrospira, and Paraflavitalea were enriched in Ss treated soil samples. The addition of Ss and Rs sclerotia activated several beneficial fungi, notably Trichoderma, Talaromyces, Clonostachys in Ss treated samples, and Vermispora, Hyalorbilia, Mortierella, Lecanicillium in Rs treated samples. Additionally, Rs treated soil samples also activated pathogenic genera, including Typhula, Fusarium, and Rhizoctonia. Sclerotia in soil modulates the microbiome and activates beneficial and pathogenic microbes. During the off-season, the Sclerotinia inoculum pressure in the soil reduces, and it is safe to grow crops next season. Whereas, in the case of Rhizoctonia infected soil, it is suggested to avoid growing crops susceptible to wilt, root rot, and blight. However, field experiments to understand the pathogen–pathogen interactions around the sclerotiosphere require further exploration. Full article

Objective: To determine the prevalence of mood and eating disorders, chronotype, and social jetlag in a cohort of women with polycystic ovarian syndrome (PCOS). Methods: A total of 70 patients, 35 with PCOS and 35 healthy controls, aged between 18 and 40 years, were included in the study. PCOS was diagnosed according to the Rotterdam criteria. Five different questionnaires, namely the “Morningness–Eveningness Questionnaire (MEQ)”, “Social Jetlag Status (SJL)”, “Night Eating Questionnaire (NEQ)”, “Beck Depression Inventory (BDI)”, and “Beck Anxiety Inventory (BAI)”, were administered to patients with and without PCOS, and the “total questionnaire scores” of both groups were compared. Results: In addition to BMI (p = 0.004), serum insulin (p < 0.001), HOMAIR (p < 0.001), total testosterone (p = 0.006), DHEAS (p = 0.004), and LH (p < 0.001) levels were significantly higher in women with PCOS than in the controls. BAI (p = 0.006), BDI (p = 0.007), and NEQ (p = 0.013) scores of participants with PCOS were significantly higher than those in the control group, while MEQ scores were significantly lower than those in the control group (p = 0.005). When categorized according to the total test scores, the number of individuals with moderate and severe anxiety was significantly higher in the PCOS group than in the control group (p = 0.030). Morningness was significantly lower in the PCOS group than in the control group, whereas eveningness was higher than that in the control group (p = 0.013). There was no difference between the PCOS and control groups in terms of the number of individuals with SJL ≥ 2 h and night eating disorders. The NEQ score was positively correlated with BAI, BMI, insulin, and HOMA-IR. Both the BDI and BAI scores were positively correlated with BMI, HOMA-IR, and total testosterone levels. Conclusions: PCOS can lead to mood, appetite, and circadian rhythm issues through variations in chronotype. PCOS-related endocrine, metabolic, and adiposity factors influence mood, eating habits, and chronotype disorders. Full article

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in reproductive-age women, is characterized by menstrual irregularities and polycystic ovarian morphology. It is also associated with insulin resistance, chronic inflammation, and oxidative stress, all of which may promote autoimmunity. Several studies have suggested a higher occurrence of antinuclear antibodies (ANA) in PCOS but the main challenge in this field is the inconsistency of findings due to heterogeneous study designs and assay methods. However, to date, no systematic review has synthesized this evidence. We conducted a systematic review to evaluate the prevalence and serum levels of ANA in women with PCOS. A comprehensive search was performed in PubMed, Embase, and Scopus, and 13 studies were ultimately included, comprising 924 women with PCOS and 1172 controls. ANA were elevated in about half of the studies, while the remainder found no significant differences between PCOS and controls. Anti-dsDNA antibodies were the most consistently investigated ANA subtype, with most studies reporting higher levels or prevalence in PCOS. For other ANA subtypes, the evidence was limited and inconclusive, largely due to methodological variability across studies. This systematic review suggests that ANA may be elevated in a subset of women with PCOS, but the current evidence remains inconsistent. These findings highlight the need for methodological standardization in ANA assessment to enable clearer conclusions and to clarify whether ANA positivity has clinical relevance in this population. Full article

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine and metabolic conditions affecting women of reproductive age. This condition affects around 20% of this demographic and is characterized by polycystic ovarian morphology, hyperandrogenism, and chronic anovulation. Obesity, impacting 40–85% of women with PCOS, exacerbates insulin resistance, increases insulin levels, and intensifies low-grade inflammation. This exacerbates the reproductive and metabolic complications associated with the condition. Recent advancements in molecular biology have underscored the significance of non-coding RNAs, including as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as crucial regulators of gene expression and prospective biomarkers for PCOS. Exosome-derived microRNAs (ex-miRNAs) have emerged as compelling candidates due to their stability in body fluids and their capacity to promote intercellular communication among adipose tissue, the ovary, and the endometrium. Research, encompassing both experimental and clinical studies, has shown that ex-miRNAs display differing expression levels in women with obesity-related PCOS. Several of these ex-miRNAs are associated with networks that govern inflammation, glucose metabolism, steroidogenesis, and folliculogenesis. Moreover, the encapsulation of these chemicals within exosomes safeguards them from enzymatic breakdown, hence augmenting their potential as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring. Despite the initial results being encouraging, challenges remain in standardising exosome separation, quantifying miRNA, and analyzing functional data within the complex pathophysiology of PCOS. This narrative review consolidates existing evidence regarding the molecular signatures of obesity-related infertility in PCOS, emphasising the growing significance of exosomal miRNAs and other non-coding RNAs, while examining their translational potential for early diagnosis and personalised therapeutic approaches. Full article