Search Results (3,407)

Ring finger protein 126 (RNF126) is a RING-type E3 ubiquitin ligase that has recently emerged as a multifaceted regulator of cellular homeostasis, stress adaptation, and disease progression. Through its structurally distinct zinc-finger and catalytic RING domains, RNF126 orchestrates substrate recognition and ubiquitin transfer, generating diverse ubiquitin linkages with both proteolytic and nonproteolytic functions. Initially characterized as a component of the protein quality control (PQC) machinery, RNF126 cooperates with chaperones such as BAG6 and UBQLN1 to eliminate mislocalized and misfolded proteins, thereby maintaining proteostasis. Beyond PQC, RNF126 plays pivotal roles in DNA damage response pathways by regulating homologous recombination, non-homologous end joining, checkpoint signaling, and genome stability through substrates, including MRE11, Ku80, RNF168, and 14-3-3σ. Genetic studies have further demonstrated its importance in embryogenesis and male fertility, and accumulating evidence has identified RNF126 as a critical driver of malignancy in multiple cancers. RNF126 promotes tumor progression by degrading or modulating key regulators, such as p21, PTEN, p53, PDKs, and LKB1, thereby enhancing proliferation, metabolic reprogramming, anoikis resistance, metastasis, and chemo/radioresistance. Intriguingly, RNF126 exhibits context-dependent functions, acting as an oncogene or tumor suppressor depending on the tissue type and substrate selection. In addition to cancer, RNF126 has been implicated in neurodegeneration, cardiac pathology, antiviral immunity and adaptive immune regulation. This review summarizes the current knowledge of RNF126 structure, ubiquitin signaling mechanisms, physiological functions, and pathological roles, while discussing emerging therapeutic strategies and future challenges for targeting RNF126 in precision medicine. Full article

Importance: Most couples who turn to assisted reproductive technology (ART) treatment do so, usually, after giving up emotionally on the chances of conceiving naturally. Others undergo ovulation induction with intrauterine insemination (IUI) and turn to ART after the latter has failed. Spontaneous conception after having experienced the exhausting process of ART, whether it was successful or not, could be very surprising and confusing for many couples. Objective: Review all the scenarios within which an unexpected spontaneous conception can occur and the likelihood of its occurrence. These are four such scenarios: (1) after being referred to ART but before the actual initiation of ART; (2) between ART cycles; (3) after a successful ART pregnancy; (4) after giving up on treatment. We have found only a systematic review on #3, but not the other three. Evidence Review: We collected all PubMed citations for the terms “spontaneous conception” and ART or IVF. Thereafter, we realized that no AI tool can filter only the relevant literature. Hence, we exhausted all possible cross-references by manual search to ensure the completeness of the search. Findings: In each of the four scenarios, spontaneous conceptions occur. Before treatment, a critical element is the length of the waiting time, as is the gap between treatments when already treated, with the cost of treatment being a critical determinant. After the conclusion of treatment, whether successful or failed, the main determinants of the chance for spontaneous conception are age, length of infertility, and the leading etiology for infertility. Overall, the chances range from as little as 2% and up to 25%, with severe male factor and a woman’s age being the most notable for low rates. Conclusion and Relevance: Each couple entering ART treatment should be informed of the chances for spontaneous conception, whether as an aid to the decision to enter or the decision to leave after a failure, and on the more cheerful side, to be aware of the chances for unplanned pregnancy after a successful treatment. Full article

Background/Objectives: Y chromosome microdeletions in the azoospermia factor (AZF) regions are a major genetic cause of severe male infertility, yet their relationship with hormonal profiles in azoospermic men remains unclear. This study aimed to investigate AZF microdeletions and associated hormonal parameters in azoospermic patients. Methods: Azoospermic patients were screened for AZFa, AZFb, and AZFc microdeletions using multiplex real-time PCR targeting sequence-tagged site (STS) markers (sY84, sY127, and sY254). Patients were categorized into AZF-negative and AZF-positive groups, with the latter further stratified according to their deletion subtype. Serum follicle-stimulating hormone (FSH), testosterone, and inhibin B levels were measured. Hormonal parameters were compared between groups using the Mann–Whitney U test, and a logistic regression analysis was performed to evaluate associations between hormonal variables and AZF deletion status. Results: AZF microdeletions were detected in 18.7% (17/91) of patients. Patients without AZF deletions showed a median FSH level of 17.40 (7.12–31.27) IU/L. In contrast, AZFc deletion carriers exhibited an intermediate median FSH level of 21.10 (16.11–26.10) IU/L and lower median inhibin B concentrations (25.50 [25.25–26.00] pg/mL) compared with AZF-negative patients (56.00 [33.50–106.50] pg/mL). Median testosterone levels in AZFc patients (3.61 [2.87–4.35] ng/mL) remained within the expected physiological range. However, no statistically significant differences were observed between the AZF subgroups for age (p = 0.262), FSH (p = 0.506), testosterone (p = 0.615), or inhibin B (p = 0.524). The logistic regression analysis also showed no significant association between hormonal parameters and AZF deletion status. Conclusions: Hormonal parameters alone are insufficient to predict the presence of AZF microdeletions in azoospermic men. These findings highlight the importance of routine genetic screening for accurate diagnosis, clinical management, and reproductive counseling in male infertility. Full article

Oocyte formation occurs successfully within a meticulously controlled follicular environment characterized by well-documented endocrine, metabolic, and paracrine signals. Yet, the immunological landscape of the follicle and its role in influencing oocyte competency has received less attention in research. Growing research indicates that the ovarian follicle functions as an immunological-active niche necessitating a precise equilibrium between controlled inflammation and targeted immune tolerance. The programmed cell death-1 (PD-1) receptor and its ligand PD-L1 constitute a crucial immune checkpoint pathway, essential for sustaining peripheral immunological tolerance and averting excessive immune activation. Despite their comprehensive research in cancer biology and maternal–fetal interactions, their possible function in the follicular microenvironment remains mostly unexamined. We propose that PD-1/PD-L1 signaling may facilitate the formation of a localized immune-tolerant milieu inside the follicle to safeguard the developing oocyte from inflammatory injury and immune-mediated stress. The disturbance of this suggested equilibrium may lead to a pro-inflammatory follicular environment, compromised granulosa cell function, and modified oocyte maturation, hence affecting fertilization and embryonic developmental potential. In clinical contexts with immunological dysregulation, such as endometriosis, polycystic ovarian syndrome, and unexplained IVF failure, such processes may be especially significant. The purpose of this narrative review is to assimilate the current comprehension of immune regulation in the follicle with the established biology of PD-1/PD-L1 and to investigate a potential correlation between immune checkpoint signaling, oocyte competence, and assisted reproductive outcomes. Considering the follicle as an immune-regulated microenvironment offers a new paradigm for comprehending infertility and identifying novel indicators or therapeutic targets. Full article

WEE2, an oocyte-specific kinase of the WEE family, is a core regulator of oocyte meiosis. It maintains germinal vesicle (GV) arrest and prevents premature meiotic resumption by phosphorylating cyclin-dependent kinase 1 (CDK1), thereby inhibiting maturation-promoting factor (MPF) activity. WEE2 also regulates exit from metaphase II (MII), ensuring orderly meiotic progression. Consequently, the functional integrity of WEE2 is essential for female reproduction. Homozygous or compound heterozygous mutations in the WEE2 gene represent a major genetic cause of total fertilization failure and primary infertility, as these mutations lead to reduced or abolished kinase activity, impair meiotic control, and disrupt oocyte maturation and embryonic development. This review systematically summarizes the protein structure, core functions, and mutation types of WEE2, along with its association with total fertilization failure and female primary infertility. It also highlights research advances in WEE2-targeted inhibitors and discusses the potential applications and future directions of WEE2 in the diagnosis and management of reproductive disorders. Full article

Background/Objectives: The rapid expansion of social media platforms has profoundly changed the way adolescents access reproductive health information. While digital environments increase accessibility to contraceptive content, they also facilitate the dissemination of misinformation, potentially influencing both contraceptive literacy and psychological well-being. The present study aimed to evaluate the relationship between sources of contraceptive information, contraceptive misinformation endorsement, contraceptive knowledge, and mental health indicators among Romanian adolescents and young adults. Methods: A cross-sectional observational study was conducted in a cohort of 210 Romanian adolescents and young adults. Participants completed a structured self-administered questionnaire assessing demographic characteristics, contraceptive information sources, digital health behaviors, contraceptive misconceptions, and contraceptive knowledge. Anxiety and depressive symptoms were evaluated using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scales. Correlation analyses and multivariable logistic regression models were performed to identify factors associated with poor contraceptive knowledge and moderate-to-severe anxiety. Results: Social media represented the primary source of contraceptive information for 58.1% of participants. Individuals relying predominantly on social media demonstrated significantly lower contraceptive knowledge questionnaire (CKQ) scores compared to those obtaining information from healthcare professionals (5.9 ± 1.8 vs. 8.1 ± 1.7, p < 0.001). Contraceptive misinformation endorsement was inversely correlated with CKQ scores (r = −0.44, p < 0.001) and positively associated with anxiety (r = 0.47, p < 0.001) and depressive symptoms (r = 0.41, p < 0.001). In multivariable analyses, primary reliance on social media (OR 2.21, 95% CI 1.12–4.34, p = 0.022) and low digital health literacy (OR 2.94, 95% CI 1.51–5.71, p = 0.001) were independently associated with poor contraceptive knowledge. Higher misinformation endorsement, infertility-related fears, and high social media exposure were independently associated with moderate-to-severe anxiety. Conclusions: Contraceptive misinformation endorsement was associated with lower contraceptive literacy and poorer psychological outcomes among adolescents and young adults. These findings highlight the growing importance of digital health literacy. However, given the cross-sectional design, the observed relationships should be interpreted as associations rather than causal effects, and longitudinal studies are required to clarify their directionality. Full article

Seasonal infertility remains a major challenge in pig production and is influenced by environmental conditions and sow parity. This study aimed to identify in-barn heat load (HL), light variability (LV), and parity as farm-specific predictors of farrowing success (FS) and litter size (LS) in purebred Large White sows raised under subtropical and tropical conditions in Brazil. Reproductive records from 2021 were obtained from two commercial farms, and in-barn temperature and illuminance were recorded using data loggers installed in gestation units. Services between March and August 2021 were analyzed using logistic regression for FS and linear regression for LS, resulting in 732 service records from Farm 1 and 233 from Farm 2. In the combined analysis, parity was associated with higher odds of FS (OR = 1.20; p = 0.003) and greater LS (β = 0.47; p < 0.001). HL was not associated with FS but showed a small positive association with LS (β = 0.28; p = 0.031). In Farm 2, LV was negatively associated with FS (OR = 0.72; p = 0.028) and LS (β = −0.59; p = 0.020). Overall, parity structure strongly shaped reproductive performance, and in-barn environmental effects were context-dependent. Full article

Endometriosis is a long-term gynecological condition marked by the growth of endometrial-like tissue outside the uterus, which undergoes proliferation, bleeding, and regeneration. This disease is associated with disrupted steroid hormone signaling, notably progesterone (P4) resistance and estradiol (E2) dominance. P4 resistance has been associated with impaired activation of the progesterone receptor (PR) and reduced transcription of P4 target genes, while elevated E2 levels induce estrogen receptor (ER)-mediated signaling, enhancing estrogen-dependent lesion growth. This hormonal imbalance contributes to a pro-inflammatory microenvironment, chronic pelvic pain, infertility, and enhanced neuroangiogenesis. Emerging evidence indicates that the coordinated regulation of neurotrophins and sex hormones promotes nerve fibers and blood vessel growth and invasion within endometriotic lesions. P4 and E2 have been shown to modulate the expression of key neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This review presents current evidence on the interplay between neurotrophins and ovarian steroids in endometriosis, with a specific focus on their contribution to neuroangiogenesis and pain pathophysiology. The review includes articles in English containing the Medical Subject Headings (MeSH) terms: “endometriosis”, “neurotrophins”, “nerve growth factor”, “brain-derived neurotrophic factor”, “neuroangiogenesis”, “progesterone”, and “estradiol”, found in the PubMed database published between 2000 and 24 May 2026. This review included a range of original research articles, systematic reviews, meta-analyses, prospective observational studies, case–control studies, and review papers, for a total of 122 articles. Full article

Background: Polyendocrine metabolic ovarian syndrome (PMOS/PCOS) is the most common hormonal disorder in women of reproductive age and is linked to infertility as well as long-term metabolic and psychological problems. In the Gulf Cooperation Council (GCC) region, rising obesity, dietary changes, and sedentary lifestyles may be increasing its burden. However, prevalence estimates remain highly inconsistent due to differences in diagnostic criteria and measurement methods rather than true variation in disease rates. Objective: This study aimed to describe the situation by systematically pooling available evidence on the prevalence of PMOS among women in GCC countries and by summarizing the range of clinical features reported across included studies. Methods: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched five major bibliographic databases (PubMed, Scopus, Web of Science, Cochrane Library, and Embase) and the Google Scholar search engine for observational studies published up to 1 June 2026. Studies were eligible if they reported PMOS prevalence and related clinical features among women of reproductive age residing in GCC countries. After removing duplicates and screening 570 initially identified records, 25 studies met our inclusion criteria; 24 were included in the quantitative meta-analysis after excluding one high-risk study. Risk of bias was appraised using the Joanna Briggs Institute Checklist for Prevalence Studies. A random-effects meta-analysis using the DerSimonian-Laird method, combined with the Freeman-Tukey double arcsine transformation, was used to estimate the pooled prevalence. Heterogeneity was quantified using the I² statistic and Cochran’s Q test. Subgroup analyses explored differences by country, diagnostic method, study setting, and publication period. Meta-regression was used to identify study-level factors that explained between-study variability. Results: Across 24 studies involving 77,890 women, the pooled prevalence of PMOS was 17.59% (95% CI: 12.98–23.40%). Country-level estimates ranged from 6.56% in Oman to 23.0% in Saudi Arabia. Heterogeneity across all analyses was extremely high (I² = 99.6%), and meta-regression identified the diagnostic tool as the single most important source of variation, explaining 42.7% of between-study variance. Studies using structured clinical criteria (Rotterdam or NIH) yielded prevalence estimates around 13–14%, while those relying on self-report or physician diagnosis without standardized criteria reported considerably higher figures (20–37%). Common clinical features included menstrual irregularity (up to 100% of PMOS cases in clinical cohorts), hirsutism (5–100%), acne and oily skin (17–74%), and obesity (17–73%). Awareness of PMOS among women in the region was highly variable, ranging from under 3% to nearly 100%. Conclusions: PMOS is a significant public health concern across the GCC region. The markedly higher pooled prevalence combined with high rates of obesity and metabolic risk in this population calls for urgent, coordinated action. Standardizing diagnostic practices, investing in population-level screening, and developing culturally tailored awareness programs are essential steps toward reducing the clinical and social burden of PMOS. Full article

Endometrial polyps are common benign lesions of the uterine cavity characterized by localized overgrowth of endometrial glands, stroma, and vasculature. They are mostly asymptomatic, although in some cases they cause abnormal uterine bleeding and infertility. Increasing evidence indicates that endometrial polyps represent genetically heterogeneous lesions with a multifactorial molecular basis. This review aims to analyze current knowledge on the genetic background of endometrial polyps. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles, and meta-analyses regarding the role of genetics in endometrial polyps, published in the English language with no time restrictions. References of the selected articles for possible additional articles were also screened in order to include most of the key recent evidence. This review highlights the multifactorial genetic landscape underlying the development of endometrial polyps. Current data suggest that these lesions cannot be explained by a single pathogenic mechanism, but rather arise through the interaction of chromosomal changes, somatic and germline genetic variants and dysregulated gene expression. Understanding and integrating these genetic and molecular alterations may improve future diagnostic evaluation, risk stratification, and clinical management of endometrial polyps, although most findings are not yet ready for routine clinical application. Full article

Background: Male infertility affects millions of couples, accounting for 50 percent of cases. Despite such a major contribution of the male factor, it is not properly evaluated and is often overlooked in infertility assessments. Semen analysis, which is routinely performed to assess infertility status, is unable to assess the defects at the molecular level which are important to assess the fertilizing capacity of the sperm. This study aims to determine the utility of sperm function tests as biomarkers for male infertility in addition to standard semen analysis. Methods: Thirty-five men (aged 25–45 years) were recruited and divided into two groups: those with at least one altered semen parameter (infertile group) and those with normal semen parameters but unable to conceive after more than one year of unprotected intercourse (unexplained male infertility group). The DNA Fragmentation Index (DFI), Nuclear Chromatin Decondensation Test (NCDT) and Hypoosmotic Swelling Test (HOS) were used in diagnosing sperm dysfunction in both groups. The Mann–Whitney U testand Spearman’s rank correlation were used for analyzing the parameters of the groups. A p value < 0.05 was considered statistically significant. Results: While motility and vitality were nearly identical in both groups, the infertile group showed more morphological abnormalities. The DFI was higher in the unexplained male infertility group (UMI) (82%) than in the infertile group (36%). Poor decondensation capacity was present in 27% of the unexplained male infertility group and 60% of the infertile group. Both groups’ hypoosmotic swelling values fell within the usual range. Spearman correlation analysis revealed that the NCDT showed significant positive correlations with sperm vitality (r = 0.36; p = 0.02) and morphology (r = 0.53; p = 0.001). The DFI demonstrated significant negative correlations with vitality (r = −0.45; p = 0.006) and motility (r = −0.39; p = 0.01). HOS was significantly positively correlated with motility (r = 0.56; p = 0.0004) and vitality (r = 0.57; p = 0.0003). Additionally, the NCDT and DFI showed a significant inverse correlation (r = −0.33; p = 0.04). Conclusions: These findings highlight the potential of sperm function tests as valuable diagnostic tools alongside conventional semen analysis for a more comprehensive assessment of male fertility. Full article

Three-dimensional (3D) endothelium–stromal co-cultures were established using human endometrial cells from biopsy of healthy women (n = 13) and serum samples from both healthy and endometriotic women (n = 5). For 3D construction, stromal cells were mixed with extracellular matrix components, followed by endothelial cell seeding. Morphological analysis confirmed the organization of tissue-like structures. Immunofluorescence and flow cytometry verified the expression of specific stromal and endothelial markers (Cytokeratin, Vimentin, Insulin-like growth factor-binding protein 1, and von Willebrand factor). Cell viability and proliferation increased over time, with minimal cell death. To test functional responsiveness, these co-cultures were exposed to inflammatory serum from endometriotic patients. After 48 h, cytometric bead array showed elevated levels of IL-1β, IL-6, and IL-8 in cultures treated with inflammatory serum, indicating preserved functional activity and responsiveness. By allowing detailed investigation of functional endometrial states within a physiologically relevant cellular network, this approach provides a valuable organoid-like tool to explore conditions such as implantation failure and infertility and to study the cellular interactions underlying reproductive pathologies. Full article

Male reproductive health has experienced an unprecedented decline over the past five decades, characterized by substantial reductions in sperm count and testosterone levels. This review provides a comprehensive synthesis of current evidence on the global decline in sperm count and testosterone levels, examining epidemiological trends, underlying mechanisms, environmental drivers, and clinical implications. Sperm concentration declined by 51.6% globally between 1973 and 2018, with an accelerating trajectory post-2000 (from 1.16% to 2.64% per year). Concurrently, multiple independent studies document an age-independent secular decline in testosterone, averaging 1–2% per year across diverse populations. The etiology is multifactorial, involving endocrine-disrupting chemicals (bisphenol A, phthalates, pesticides, dioxins), lifestyle factors (obesity, sedentary behavior, smoking, heat exposure), and disruption of the hypothalamic–pituitary–gonadal axis. At the cellular level, mechanisms include Sertoli and Leydig cell dysfunction, oxidative stress, mitochondrial impairment, and sperm DNA fragmentation. Integrated clinical management combining lifestyle optimization, antioxidant therapy, and targeted endocrine interventions is essential. Prevention through environmental policy and public health initiatives represents the most promising long-term strategy. Full article

This review aims to evaluate the potential of endometriosis models, especially patient-derived iPSC models, to gain deeper insights into the disease, thereby advancing our understanding and treatment of endometriosis. This comprehensive narrative review utilized a structured search of the PubMed, Scopus, and Web of Science databases, primarily covering literature published between January 2000 and May 2025. An expansive search strategy was employed to capture the full breadth of the field using keywords such as “endometriosis,” “induced pluripotent stem cells (iPSCs),” “patient-derived organoids,” “disease modeling,” and “epigenetics” without restrictive filtering, ensuring the integration of both foundational theories and emerging biotechnological advances. In total, over 170 peer-reviewed publications were analyzed, ranging from landmark genomic meta-analyses that have identified significant risk loci to state-of-the-art 3D-culture systems for modeling patient-specific endometrial disease. By synthesizing these diverse sources, the review bridges the gap between traditional anatomical classifications and modern molecular modeling to evaluate the potential of iPSC platforms for personalized medicine and therapeutic discovery. Endometriosis is a multifactorial gynecological condition that affects 176 million women worldwide and can significantly impair quality of life. It occurs when endometrium-like tissue grows outside the uterus, responsive to ovarian hormones, causing inflammation, pain, and discomfort, and leading to fibrotic tissue. World Health Organization estimates indicate that 6–10% of women suffer from this disorder, which can cause infertility and increase the risk of developing various types of cancer and autoimmune disorders. The use of patient-derived iPSC models serves to gain deeper insights into the disease by mimicking the endometrial tissue or lesions observed in affected individuals, thereby advancing our understanding and treatment of endometriosis. Full article