Impaired Semen Quality in Patients with Chronic Prostatitis.

Chronic prostatitis/chronic pelvic pain syndrome CP/CPPS is a rather common condition and in recent years many studies have shown contradictory results regarding its impact on semen quality. This prospective cohort study set out to investigate how CP/CPPS affected the parameters of semen in a prospective cohort of patients compared with the WHO 2021 reference group. From 2013 to 2022, a total of 1071 patients with suspicion of CP/CPPS received a comprehensive andrological examination.

Targeting Host Tyrosine Kinase Receptor EPHA2 Signaling Affects Uropathogen Infection in Human Bladder Epithelial Cells.

Urinary tract infections (UTIs) affect a major proportion of the world population but have limited non-antibiotic-based therapeutic and preventative strategies against UTIs. Facultative intracellular uropathogens such as strains of uropathogenic , , , are well-known uropathogens causing UTIs. These pathogens manipulate several host-signaling pathways during infection, which contributes to recurrent UTIs and inappropriate antibiotic application.

Interleukin-1 receptor associated kinase 1 (IRAK1) is epigenetically activated in luminal epithelial cells in prostate cancer.

The use of immune adjuvants such as toll-like receptor (TLR) agonists reflects a novel strategy in prostate cancer (PCa) therapy. However, interleukin-1 receptor associated kinase 1 (IRAK1), a central effector of TLR signaling, has been shown to be responsible for resistance to radiation-induced tumor cell death. In order to better understand the function and epigenetic regulation of IRAK1 in PCa, we performed cell culture experiments together with integrative bioinformatic studies using the latest single-cell RNA-sequencing data of human PCa and normal prostate (NOR), and data from The Cancer Genome Atlas.

Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells.

Non-mesenchymal pancreatic cells are a potential source for cell replacement. Their transdifferentiation can be achieved by triggering epigenetic remodeling through e. g.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome Leads to Impaired Semen Parameters, Increased Sperm DNA Fragmentation and Unfavorable Changes of Sperm Protamine mRNA Ratio.

Background: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a frequent disease affecting men of every age and accounting for a great number of consultations at urology departments. Previous studies suggested a negative impact of CP/CPPS on fertility. As increasing attention has been attributed to additional aspects, such as sperm DNA integrity and sperm protein alterations, besides the WHO standard semen analysis when assessing male fertility, in this prospective study, we aimed to further characterize the fertility status in CP/CPPS patients with a focus on these parameters.

H4K20me3 marks distal intergenic and repetitive regions in human mature spermatozoa.

Sperm histones represent an essential part of the paternally transmitted epigenome, but uncertainty exists about the role of those remaining in non-coding and repetitive DNA. We therefore analyzed the genome-wide distribution of the heterochromatic marker H4K20me3 in human sperm and somatic (K562) cells. To specify the function of sperm histones, we compared all H4K20me3-containing and -free loci in the sperm genome.

The Clinical Application and Potential Roles of Circulating Tumor Cells in Bladder Cancer and Prostate Cancer.

Circulating tumor cells (CTCs) are considered to be promising biomarkers in malignant diseases. Recently, molecular profiles of CTCs in prostate cancer (PCa) and the role of CTCs in neoadjuvant chemotherapy and transurethral resections of bladder cancer (BCa) are intensely studied. However, localized PCa and nonmuscle-invasive BCa are less investigated and discussed.

Elevated seminal plasma estradiol and epigenetic inactivation of and is associated with CP/CPPS.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III ( 50; median age 39.

Impairment of IGF2 gene expression in prostate cancer is triggered by epigenetic dysregulation of IGF2-DMR0 and its interaction with KLF4.

Background: Human cancer cells often exhibit impaired IGF2 expression and the underlying mechanisms are multifaceted and complex. Besides the well-known imprinting control region IGF2/H19-ICR, the involvement of a differentially methylated region in the promoter P0 of IGF2 gene (IGF2-DMR0) has been suggested. Here, we evaluate several mechanisms potentially leading to up- and/or down-regulation of IGF2 expression in prostate cancer and present a novel role of Kruppel-like factor 4 (KLF4) as a transcriptional regulator of IGF2 binding in IGF2-DMR0.

Unexplained recurrent miscarriages are associated with an aberrant sperm protamine mRNA content.

Study Question: Are unexplained recurrent miscarriages associated with abnormal protamine-1 and protamine-2 mRNA levels in spermatozoa?

Summary Answer: Both protamine-1 and protamine-2 mRNA levels as well as the protamine-1 to protamine-2 mRNA ratio in spermatozoa from men whose female partners experienced two or more consecutive miscarriages were significantly different compared to those from both healthy control men and subfertile couples undergoing IVF/ICSI.

What Is Known Already: Aberrant sperm protamine ratios are known to be associated with male-factor infertility. Data from this study suggest that the protamine mRNA ratio may additionally affect early embryo development.

The impact of autophagy in spermiogenesis.

Autophagy is an evolutionarily conserved self-digestion process which is essential to keep basal homeostasis in a cell. During this process, degradation and recycling of many cytoplasmic components including the long-lived, unnecessary or aggregated proteins and damaged organelles is achieved through lysosomal machinery. Autophagy has a critical role for lower eukaryotic organisms such as yeast to survive and adapt to nutrient starvation conditions.

Chronic Prostatitis Affects Male Reproductive Health and Is Associated with Systemic and Local Epigenetic Inactivation of C-X-C Motif Chemokine 12 Receptor C-X-C Chemokine Receptor Type 4.

Unlabelled: Background/Aims/Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has detrimental effects on the quality of life including the aspect of sexual dysfunction. The aim of the study was to identify if there was an adverse effect on the male genital compartment and if there are systemic or compartment-specific local signals for epigenetic dysregulation of inflammatory factors in CP/CPPS patients.

Methods: One hundred five NIH IIIb CP/CPPS patients and 41 healthy men were recruited and underwent investigations of urines, semen and blood.

Epigenetics in male reproduction: effect of paternal diet on sperm quality and offspring health.

Epigenetic inheritance and its underlying molecular mechanisms are among the most intriguing areas of current biological and medical research. To date, studies have shown that both female and male germline development follow distinct paths of epigenetic events and both oocyte and sperm possess their own unique epigenomes. Fertilizing male and female germ cells deliver not only their haploid genomes but also their epigenomes, which contain the code for preimplantation and postimplantation reprogramming and embryonal development.

Developmental origins of male subfertility: role of infection, inflammation, and environmental factors.

Male gamete development begins with the specification of primordial cells in the epiblast of the early embryo and is not complete until spermatozoa mature in the epididymis of adult males. This protracted developmental process involves extensive alteration of the paternal germline epigenome. Initially, epigenetic reprogramming in fetal germ cells results in removal of most DNA methylation, including parent-specific epigenetic information.

TET enzymes are successively expressed during human spermatogenesis and their expression level is pivotal for male fertility.

Study Question: Are ten-eleven-translocation (TET) 1-3 family enzymes involved in human spermatogenesis and do they impact male fertility?

Summary Answer: TET1, TET2 and TET3 are successively expressed at different stages of human spermatogenesis, and their expression levels associate with male fertility.

What Is Known Already: Spermatogenesis is a complex cell differentiation process accompanied by a drastic epigenetic remodeling. TET1-3 dioxygenases are essential for active DNA demethylation in the paternal pronucleus and in embryonic stem cells.

Uniformity of nucleosome preservation pattern in Mammalian sperm and its connection to repetitive DNA elements.

Nucleosome-to-protamine exchange during mammalian spermiogenesis is essential for compaction and protection of paternal DNA. It is interesting that, depending on the species, 1% to 15% of nucleosomes are retained, but the generalizability and biological function of this retention are unknown. Here, we show concordantly in human and bovine that nucleosomes remained in sperm chromatin predominantly within distal intergenic regions and introns and associated with centromere repeats and retrotransposons (LINE1 and SINEs).

Bacterial prostatitis.

Objectives: The prostatitis syndrome is classified into bacterial prostatitis (acute and chronic), chronic pelvic pain syndrome and asymptomatic prostatitis. The aim of this report is to review current management standards for bacterial prostatitis.

Methods: A research was performed on literature dealing with acute and chronic bacterial prostatitis.

Analysing the sperm epigenome: roles in early embryogenesis and assisted reproduction.

An understanding of the epigenetic mechanisms involved in sperm production and their impact on the differentiating embryo is essential if we are to optimize fertilization and assisted reproduction techniques in the future. Male germ cells are unique in terms of size, robustness, and chromatin structure, which is highly condensed owing to the replacement of most histones by protamines. Analysis of sperm epigenetics requires specific techniques that enable the isolation of high quality chromatin and associated nucleic acids.

Epigenetic down regulation of RASSF10 and its possible clinical implication in prostate carcinoma.

Background: Ras association domain family (RASSF) comprises several tumor suppressor genes, which are often epigenetically inactivated in human tumors. Here, we aim to analyze the relevance of the recently identified member RASSF10 in prostate carcinogenesis.

Methods: RASSF10 promoter methylation and mRNA expression were investigated by bisulfite-pyrosequencing and qRT-PCR, respectively, in prostate carcinoma (PCa) cell lines (LNCaP, 22Rv1, DU-145) and in 83 primary PCa and 53 primary benign prostatic hyperplasia (BPH) tissues obtained after radical prostatectomy.

Short-time glucose exposure of embryonic carcinoma cells impairs their function as terminally differentiated cardiomyocytes.

The fetal and postnatal phenotype is influenced by developmental conditions experienced prenatally. Among prenatal development metabolic factors are of particular importance as they are supposed to predispose for pathophysiological alterations later in life and to pioneer functional impairment in senescence (metabolic programming). Till now the mechanisms of metabolic programming are not well understood.

Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences.

Background: The Ras association domain family (RASSF) encodes for distinct tumor suppressors and several members are frequently silenced in human cancer. In our study, we analyzed the role of RASSF2, RASSF3, RASSF4, RASSF5A, RASSF5C and RASSF6 and the effectors MST1, MST2 and WW45 in thyroid carcinogenesis.

Results: Frequent methylation of the RASSF2 and RASSF5A CpG island promoters in thyroid tumors was observed.

Protein kinase A-mediated phosphorylation of the RASSF1A tumour suppressor at Serine 203 and regulation of RASSF1A function.

Epigenetic inactivation of the Ras-Association Domain Family 1A (RASSF1A) gene is one of the most frequent alterations detected in cancer. The tumour suppressor function of RASSF1A contributes to cell cycle progression, microtubule stabilisation and apoptotic signalling. Here we investigated the putative phosphorylation sites of RASSF1A and the functional consequences.

Frequent aberrant methylation of the imprinted IGF2/H19 locus and LINE1 hypomethylation in ovarian carcinoma.

Epigenetic alteration of tumor-related genes through changes of DNA methylation is a hallmark for carcinogenesis and aberrant DNA methylation modulates the activity of tumor suppressor genes, imprinted genes and repetitive elements. In ovarian carcinoma, frequent loss of imprinting or aberrant methylation of repetitive elements were reported, however, combined analysis were not performed. We analyzed the aberrant methylation of a differentially methylated region (DMR0) and a CTCF binding site of the IGF2-H19 locus and methylation of LINE1 and Satellite 2 in 22 primary ovarian carcinomas (OC) and controls by a quantitative bisulfite restriction analysis (QUBRA).