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Despite that the SARS-CoV-2 pandemic has been controlled, it has affected a large proportion of the population, raising some concerns about potential sequelae in men at reproductive age. To contribute to the clarification of this issue, we performed a retrospective study comparing semen parameters values before and after confirmed SARS-CoV-2 infection in a large cohort of infertile men, compared to a control group that did not undergo SARS-CoV-2 infection. Wilcoxon test on paired samples and general linear regression model showed that SARS-CoV-2 infection has a detrimental effect on semen volume values (p < 0.005). However, semen volume seems to be significantly lower only during the first spermatogenic cycle after SARS-COV-2 infection (p < 0.005) and mainly in unvaccinated patients (p < 0.05). In addition, we detected alterations in progressive motility in patients infected with the alpha SARS-COV-2 strain (p < 0.05). In conclusion, our results show that although SARS-CoV-2 has a small effect on semen volume and sperm motility in infertile men, depending on the infectious strain or vaccination status, pre-infection values of semen parameters appear to be restored over one spermatogenic cycle after infection. [ABSTRACT FROM AUTHOR]

Primary open-angle glaucoma (POAG) is a complex disease with a strong hereditably component. Several genetic variants have recently been associated with POAG, partially due to technological improvements such as next-generation sequencing (NGS). The aim of this study was to genetically analyze patients with POAG to determine the contribution of rare variants and hypomorphic alleles associated with glaucoma as a future method of diagnosis and early treatment. Seventy-two genes potentially associated with adult glaucoma were studied in 61 patients with POAG. Additionally, we sequenced the coding sequence of CYP1B1 gene in 13 independent patients to deep analyze the potential association of hypomorphic CYP1B1 alleles in the pathogenesis of POAG. We detected nine rare variants in 16% of POAG patients studied by NGS. Those rare variants are located in CYP1B1, SIX6, CARD10, MFN1, OPTC, OPTN, and WDR36 glaucoma-related genes. Hypomorphic variants in CYP1B1 and SIX6 genes have been identified in 8% of the total POAG patient assessed. Our findings suggest that NGS could be a valuable tool to clarify the impact of genetic component on adult glaucoma. However, in order to demonstrate the contribution of these rare variants and hypomorphic alleles to glaucoma, segregation and functional studies would be necessary. The identification of new variants and hypomorphic alleles in glaucoma patients will help to configure the genetic identity of these patients, in order to make an early and precise molecular diagnosis. [ABSTRACT FROM AUTHOR]

Proteomic methodologies offer a robust approach to identify and quantify thousands of proteins from semen components in both fertile donors and infertile patients. These strategies provide an unprecedented discovery potential, which many research teams are currently exploiting. However, it is essential to follow a suitable experimental design to generate robust data, including proper purification of samples, appropriate technical procedures to increase identification throughput, and data analysis following quality criteria. More than 6000 proteins have been described so far through proteomic analyses in the mature sperm cell, increasing our knowledge on processes involved in sperm function, intercommunication between spermatozoa and seminal fluid, and the transcriptional origin of the proteins. These data have been complemented with comparative studies to ascertain the potential role of the identified proteins on sperm maturation and functionality, and its impact on infertility. By comparing sperm protein profiles, many proteins involved in the acquisition of fertilizing ability have been identified. Furthermore, altered abundance of specific protein groups has been observed in a wide range of infertile phenotypes, including asthenozoospermia, oligozoospermia, and normozoospermia with unsuccessful assisted reproductive techniques outcomes, leading to the identification of potential clinically useful protein biomarkers. Finally, proteomics has been used to evaluate alterations derived from semen sample processing, which might have an impact on fertility treatments. However, the intrinsic heterogeneity and inter-individual variability of the semen samples have resulted in a relatively low overlap among proteomic reports, highlighting the relevance of combining strategies for data validation and applying strict criteria for proteomic data analysis to obtain reliable results. This mini-review provides an overview of the most critical steps to conduct robust sperm proteomic studies, the most relevant results obtained so far, and potential next steps to increase the impact of sperm proteomic data. [ABSTRACT FROM AUTHOR]

Neurological disorders (ND) are diseases that affect the brain and the central and autonomic nervous systems, such as neurodevelopmental disorders, cerebellar ataxias, Parkinson's disease, or epilepsies. Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. Whole exome sequencing (WES) is widely regarded as the current technology of choice for diagnosing monogenic ND. The introduction of NGS allows for rapid and inexpensive large-scale genomic analysis and has led to enormous progress in deciphering monogenic forms of various genetic diseases. The simultaneous analysis of several potentially mutated genes improves the diagnostic process, making it faster and more efficient. The main aim of this report is to discuss the impact and advantages of the implementation of WES into the clinical diagnosis and management of ND. Therefore, we have performed a retrospective evaluation of WES application in 209 cases referred to the Department of Biochemistry and Molecular Genetics of the Hospital Clinic of Barcelona for WES sequencing derived from neurologists or clinical geneticists. In addition, we have further discussed some important facts regarding classification criteria for pathogenicity of rare variants, variants of unknown significance, deleterious variants, different clinical phenotypes, or frequency of actionable secondary findings. Different studies have shown that WES implementation establish diagnostic rate around 32% in ND and the continuous molecular diagnosis is essential to solve the remaining cases. [ABSTRACT FROM AUTHOR]