Abstract. Infertility is a significant problem for human reproduction, with males and females equally affected. However, the molecular mechanisms underlying male infertility remain unclear. Spermatogenesis is a highly complex process involving mitotic cell division, meiosis cell division and spermiogenesis; during this period, unique and extensive chromatin and epigenetic modifications occur to bring about specific epigenetic profiles in spermatozoa. It has recently been suggested that the dysregulation of epigenetic modifications, in particular the methylation of sperm genomic DNA, may serve an important role in the development of numerous diseases. The present study is a comprehensive review on the topic of male infertility, aiming to elucidate the association between sperm genomic DNA methylation and poor semen quality in male infertility. In addition, the current status of the genetic and epigenetic determinants of spermatogenesis in humans is discussed. Contents1. Introduction 2. DNA methylation 3. DNA methylation and spermatogenesis 4. DNA methylation and genomic imprinting 5. DNA methylation and male infertility 6. Conclusion IntroductionEpigenetics is the study of genomic structural modifications that affect gene expression without altering the underlying nucleotide sequence (1-3). Epigenetic mechanisms involved in the regulation of gene expression include the regulation of non-coding RNA, chromatin remodeling, DNA methylation and histone modifications (4,5). Of these mechanisms, DNA methylation has been implicated in numerous biological functions, such as the development of spermatozoa and early embryos, and the repression of endogenous retrotransposons, while it also has a wide range of effects in gene expression (2,3,6). The dysregulation of DNA methylation has previously been associated with various human disorders, and has been shown to increase the risk of fertilization failure, dysfunction in embryogenesis, perinatal mortality, congenital abnormalities, preterm birth and low birth weight (7-11). The present review assesses the significance of DNA methylation in spermatogenesis in order to elucidate the association between the dysregulation of DNA methylation and male infertility. This may provide a basis for the prevention and treatment of male infertility, as well as permit the evaluation of the epigenetic quality of sperm in order to reduce the risk of epigenetic diseases in cases where conception is performed by assisted reproductive technology (ART). DNA methylationEpigenetic mechanisms are critical regulators of gene expression during spermatogenesis that may influence male fertility (12-14). Cytosine, a key DNA base, is methylated at the position, typically in the context of CpG dinucleotides. The methylation of constitutive heterochromatic and promoter regions is generally associated with reduced gene transcription (Fig. 1A) (15-18). Therefore, DNA methylation is a type of epigenetic modification that can effectively promote gene silencing (Fig. 1B). The methyl group for this chemical modif...

Male infertility is a complex, multifactorial and polygenic disease that contributes to ~50% cases of infertility. Previous studies have demonstrated that excess weight and obesity factors serve an important role in the development of male infertility. An increasing number of studies have reported that resveratrol may regulate the response of cells to specific stimuli that induce cell injury, as well as decrease germ cell apoptosis in mice or rats. In the present study, the semen quality and serum sex hormone levels were evaluated in 324 men, which included 73 underweight, 82 normal weight, 95 overweight and 74 obese men. All patients were referred to The Reproductive Medicine Center of Shanxi Women and Infants Hospital (Taiyuan, China) between January 2013 and January 2015. The aim of the present study was to investigate the effects of resveratrol treatment on the motility, plasma zinc concentration and acrosin activity of sperm from obese males. The sperm concentration, normal sperm morphology, semen volumes, DNA fragmentation rates and testosterone levels in men from the overweight and obese groups were markedly decreased when compared with men in the normal weight group. In addition, the progressive motility, seminal plasma zinc concentration and spermatozoa acrosin activity were notably decreased in the obese group compared with the normal weight group. However, estradiol levels were significantly increased in the overweight, obese and underweight groups compared with the normal weight group. Notably, semen samples from obese males with astenospermia treated with 0–100 µmol/l resveratrol for 30 min demonstrated varying degrees of improvement in sperm motility. When these semen samples were treated with 30 µmol/l resveratrol, sperm motility improved when compared to other doses of resveratrol. Therefore, 30 µmol/l resveratrol was selected for further experiments. Upon treatment of semen samples with resveratrol (30 µmol/l) for 30 min, the seminal plasma zinc concentration and spermatozoa acrosin activity increased significantly in the experimental group compared with the control group. These data suggest that male obesity negatively impacts on male reproductive potential, not only through altering hormone levels, but also by directly altering sperm function. In addition, resveratrol may have a therapeutic and protective effect against obesity-induced abnormalities in semen.

Background:Menopausal symptoms and sleep difficulty were physiological processes that were affected by genetic and other factors. This study was to investigate the prevalence of menopausal symptoms and sleep quality in menopausal transition (MT) and postmenopause (PM) women in Taiyuan, Shanxi.Methods:A community-based survey of women's menopausal symptoms and sleep quality was conducted between July 2012 and May 2013 at six municipal districts of Taiyuan, Shanxi. A sample of 2429 women aged 40–59 years was divided into four groups: early MT, late MT, early PM, and late PM. Sleep quality in the past 2 weeks before the interview was recorded. The data were analyzed using SPSS 16.0.Results:The prevalence of menopausal symptoms was 49.8%. Mild, moderate, and severe symptoms were observed in 28.9%, 18.5%, and 2.5% of participants, respectively. The highest prevalence of menopausal symptoms occurred in the early postmenopausal stage; the subsequences were the late postmenopausal stage and the early MT stage. Interestingly, among the 13 items of modified Kupperman index, the five most common symptoms were fatigue, arthralgia and myalgia, decreased libido, insomnia, and nervousness. Meanwhile, 55% perimenopausal women had poor sleep.Conclusions:Menopausal symptoms are common but mild among women in Taiyuan, Shanxi during MT and PM. In these stages, the prevalence of poor sleep is high.

IntroductionRecent studies have shown much progress in the research of exosomes in AIDs. However, there is no bibliometric analysis in this research field. This study aimed to provide a bibliometrics review of the knowledge structure and research hotspots of neutrophil extracellular traps (NETs) in autoimmune diseases (AIDs).MethodsArticles relevant to NETs in AIDs from 2010 to 2022 were retrieved through the Web of Science Core Collection (WoSCC) database. This bibliometric analysis was performed by VOSview, CiteSpace, and Scimago Graphica.ResultsA total of 289 papers analyzed in this research were from 493 organizations in 47 countries by 1537 authors. They were published in 133 journals and cited 20,180 citations from 2,465 journals. The number of annual publications in this field is growing steadily and rapidly, with the United States, China and Germany leading the research effort. Frontiers in Immunology and Journal of Immunology have significantly impacted research in this field. Kaplan, Mariana J, from the National Institutes of Health (The United States), has the most published articles, and Brinkmann, v, from Max Planck Institute for Infection Biology (Germany), is the most co-cited author. Systemic lupus erythematosus and rheumatoid arthritis are the leading topics in this field. The trend of clinical application in the future is the development of new therapies by controlling NETs in the progression of AIDs.ConclusionsOur study summarized the research trends and developments of NETs in AIDs in recent years and would provide a reference for scholars in this field.

Bladder cancer (BC) is one of the most common urogenital malignancies. However, present studies of its multiple gene interaction and cellular pathways remain unable to accurately verify the genesis and the development of BC. The aim of the present study was to investigate the genetic signatures of BC and identify its potential molecular mechanisms. The gene expression profiles of GSE31189 were downloaded from the Gene Expression Omnibus database. The GSE31189 dataset contained 92 samples, including 52 BC and 40 non-cancerous urothelial cells. To further examine the biological functions of the identified differentially expressed genes (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network was mapped using Cytoscape software. In total, 976 DEGs were identified in BC, including 457 upregulated genes and 519 downregulated genes. GO and KEGG pathway enrichment analyses indicated that upregulated genes were significantly enriched in the cell cycle and the negative regulation of the apoptotic process, while the downregulated genes were mainly involved in cell proliferation, cell adhesion molecules and oxidative phosphorylation pathways (P<0.05). From the PPI network, the 12 nodes with the highest degrees were screened as hub genes; these genes were involved in certain pathways, including the chemokine-mediated signaling pathway, fever generation, inflammatory response and the immune response nucleotide oligomerization domain-like receptor signaling pathway. The present study used bioinformatics analysis of gene profile datasets and identified potential therapeutic targets for BC.