Agarwal A, et al. World J Mens Health. 2019 Sep;37(3):296-312. https://doi.org/10.5534/wjmh.190055

Little is known about the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility. To compare the taxonomic and functional profiles of the gut, semen, and urine microbiomes of infertile and fertile men. We prospectively enrolled 25 men with primary idiopathic infertility and 12 healthy men with proven paternity, and we collected rectal swabs, semen samples, midstream urine specimens, and experimental controls. We performed comprehensive semen analysis, 16S rRNA sequencing for quantitative high-resolution taxonomy, and shotgun metagenomics with a median of 140 million reads per sample for functional metabolic pathway profiling. We identified a diverse semen microbiome with modest similarity to the urinary microbiome. Infertile men harbored increased seminal α-diversity and distinct β-diversity, increased seminal Aerococcus, and decreased rectal Anaerococcus. Prevotella abundance was inversely associated with sperm concentration, and Pseudomonas was directly associated with total motile sperm count. Vasectomy appeared to alter the seminal microbiome, suggesting a testicular or epididymal contribution. Anaerobes were highly over-represented in the semen of infertile men with a varicocele, but oxidative stress and leukocytospermia were associated with only subtle differences. Metagenomics data identified significant alterations in the S-adenosyl-L-methionine cycle, which may play a multifaceted role in the pathogenesis of infertility via DNA methylation, oxidative stress, and/or polyamine synthesis. This pilot study represents the first comprehensive investigation into the microbiome in male infertility. These findings provide the foundation for future investigations to explore causality and identify novel microbiome-based diagnostics and therapeutics for men with this complex and emotionally devastating disease. We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future.

Despite being first described two thousand years ago, the varicocele remains a controversial multifaceted disease process with numerous biological consequences including infertility, hypogonadism, and chronic orchidalgia. The underlying mechanisms remain poorly understood and likely include hypoxia, oxidative stress, hyperthermia, anatomical aberrations, and genetics as primary components. Despite a high prevalence amongst asymptomatic fertile men, varicoceles paradoxically also represent the most common correctable cause for male infertility. In this systematic review we discuss the rich historical aspects of the varicocele and the contemporary data regarding its clinical manifestations. We performed a systematic literature review with the goal of comparing outcomes and complication rates of each of the major surgical approaches as they relate to infertility and pain. We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant systematic literature review for manuscripts focused on varicocele and its biological consequences. We identified 112 studies suitable for qualitative analysis and included 56 of these for quantitative analysis, with an emphasis on infertility and chronic pain outcomes. Taken together, the clinical work to date suggests that the highest fertility rates and the lowest complication rates are associated with the microsurgical subinguinal surgical approach to varicocelectomy. In all, 26-40% of patients undergoing varicocelectomy will successfully achieve short-term spontaneous pregnancy, and up to 90% of all patients undergoing varicocelectomy for pain will have improvement and/or resolution of their symptoms. Taken together, the data support an ongoing role for varicocelectomy in both of these clinical arenas.

Purpose of review: Contrary to historic dogma, many tissues and organs in the human body contain a resident population of bacteria, fungi, and viruses collectively known as the microbiome. The microbiome plays a role in both homeostatic symbiosis and also pathogenic dysbiosis in a wide array of diseases. Our understanding of the relationship between the microbiome and male factor infertility is in its infancy but is slowly evolving. Recent findings: Recent literature indicates that semen (and likely the testis) is not sterile and contains a distinct microbiome, and these changes in its composition are associated with alterations in semen quality and fertility status. Preliminary investigation indicates that manipulating the human microbiome may have implications in improving semen parameters and fertility. Summary: In this review, we describe relationships between the microbiome and the genitourinary system, discuss the prior work on the relationship among bacteriospermia, leukocytospermia and male factor infertility, and summarize the current literature utilizing 16s rRNA-based next-generation sequencing on the seminal and testicular microbiome. We explore the specific microbial taxa implicated in various aspects of spermatic dysfunction and introduce preliminary evidence for therapeutic approaches to alter the microbiome and improve fertility status.

Opinion statement The adult mammalian heart has limited capacity for regeneration, and any major injury such as a myocardial infarction results in the permanent loss of up to 1 billion cardiomyocytes. The field of cardiac cell therapy aims to replace these lost contractile units with de novo cardiomyocytes to restore lost systolic function and prevent progression to heart failure. Arguably, the ideal cell for this application is the human cardiomyocyte itself, which can electromechanically couple with host myocardium and contribute active systolic force. Pluripotent stem cells from human embryonic or induced pluripotent lineages are attractive sources for cardiomyocytes, and preclinical investigation of these cells is in progress. Recent work has focused on the efficient generation and purification of cardiomyocytes, tissue engineering efforts, and examining the consequences of cell transplantation from mechanical, vascular, and electrical standpoints. Here we discuss historical and contemporary aspects of pluripotent stem cell-based cardiac cell therapy, with an emphasis on recent preclinical studies with translational goals.

This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that H19 methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.