SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients.

BACKGROUND: Short- and long-term implications of SARS-CoV-2 on the quality of the sperm and the results of this on fertility remain largely unknown due to lack of longitudinal studies. In this longitudinal observational cohort study, we aimed to analyse the differential effect and the impact of SARS-CoV-2 infection on different semen quality parameters. METHODS: Sperm quality was assessed using the World Health Organization criteria, DNA damage to sperm cells by quantifying the DNA fragmentation index (DFI) and the high-density stainability (HDS), IgA- and IgG-anti-sperm antibodies (ASA) were assessed with light microscopy. FINDINGS: SARS-CoV-2 infection was associated with sperm parameters that were independent of spermatogenic cycle like progressive motility, morphology, DFI and HDS, as well as spermatogenic cycle dependent parameters such as sperm concentration. Detection of IgA- and IgG-ASA allowed classification of patients in three different groups according to its sequence of appearance in sperm during post-COVID-19 follow-up. The maximum progressive motility was lowest during follow-up in patients without ASA (41.9%), intermediate in patients with only IgA-ASA (46.2%) and highest inpatients who had both IgA- and IgG-ASA (54.9%). INTERPRETATION: SARS-CoV-2 infection was associated with changes of all analysed sperm parameters to a different degree which is also observed in their return to normality and is suggestive of individual variations in the patient's immune system performance. Firstly, sperm production is decreased through temporal immune mediated arrest of active meiosis, and secondly immune induced sperm DNA damage prevents fertilization if transferred to the oocyte. Both mechanisms are temporal, and most sperm parameters return to baseline after infection. FUNDING: AML (R20-014), Femicare.

Effect of BNT162b2 mRNA COVID-19 vaccine on sperm morphokinetics and DNA integrity: A prospective observational study in Japan

Objective: To assess whether the coronavirus disease 2019 (COVID-19) mRNA vaccine affects sperm morphokinetics using a computer-assisted semen analyzer and other semen parameters using a sperm chromatin structure assay. Method(s): Healthy male volunteers in two Japanese clinics between May 2021 and December 2021 were prospectively analyzed. Participants donated sperm twice, two days apart, in the following phases: before vaccination, 2 weeks after the first vaccine dose, and 2, 4, and 12 weeks after the second dose. Basic sperm parameters, sperm motility characteristics, and the percentage of DNA-damaged sperm were compared among the different phases. Result(s): Ninety-six semen samples from ten volunteers, who were vaccinated with the BNT162b2 mRNA vaccine, were evaluated. There were no significant differences between any phases in basic semen findings and parameters of the sperm chromatin structure assays. Regarding sperm motion characteristics, the average linear velocity, beat-cross frequency, and sperm motility index significantly decreased after the second vaccine dose (P=0.018, P=0.003, and P=0.027, respectively), with no significant differences between any two phases by post-hoc pairwise comparisons. Conclusion(s): After COVID-19 mRNA vaccination, while sperm motion characteristics might fluctuate, no apparent deterioration of basic sperm parameters or sperm DNA integrity was observed. Given the adverse effects of COVID-19 on sperm, our findings suggest that there might be no reason to refrain from vaccination for healthy individuals.Copyright © 2023 Asian Pacific Journal of Reproduction Produced by Wolters Kluwer- Medknow.

Dynamics of Viral and Host 3D Genome Structure upon Infection.

Eukaryotic chromatin is highly organized in the 3D nuclear space and dynamically regulated in response to environmental stimuli. This genomic organization is arranged in a hierarchical fashion to support various cellular functions, including transcriptional regulation of gene expression. Like other host cellular mechanisms, viral pathogens utilize and modulate host chromatin architecture and its regulatory machinery to control features of their life cycle, such as lytic versus latent status. Combined with previous research focusing on individual loci, recent global genomic studies employing conformational assays coupled with high-throughput sequencing technology have informed models for host and, in some cases, viral 3D chromosomal structure re-organization during infection and the contribution of these alterations to virus-mediated diseases. Here, we review recent discoveries and progress in host and viral chromatin structural dynamics during infection, focusing on a subset of DNA (human herpesviruses and HPV) as well as RNA (HIV, influenza virus and SARS-CoV-2) viruses. An understanding of how host and viral genomic structure affect gene expression in both contexts and ultimately viral pathogenesis can facilitate the development of novel therapeutic strategies.

6th International Leh Symposium

The proceedings contain 49 papers. The topics discussed include: eliminating senescent cells can promote pulmonary hypertension development and progression;roles of chromatin structure, transcription factors, and epigenetic regulators in the persistently activated phenotype of pulmonary vascular cells in hypoxia- induced pulmonary hypertension;Tibetan adaptation to high altitude: what we know and what is still missing?;age differences in cardiopulmonary adaptations to high altitude and Tibetan women's reproductive success;endothelial pas domain protein 1 variants regulate adaptation and maladaptation mechanisms under hypoxia;hemoglobin increase with altitude in different world regions;membrane and capillary component of lung diffusion capacity in high-altitude natives;hypoxia conditioning for preacclimatization, prophylaxis, and therapy;and COVID-19 with respect to protection or risk at high altitude: a global perspective.

Breaking boundaries: Pan BETi disrupt 3D chromatin structure, BD2-selective BETi are strictly epigenetic transcriptional regulators.

BACKGROUND: Bromodomain and extraterminal proteins (BETs) are more than just epigenetic regulators of transcription. Here we highlight a new role for the BET protein BRD4 in the maintenance of higher order chromatin structure at Topologically Associating Domain Boundaries (TADBs). BD2-selective and pan (non-selective) BET inhibitors (BETi) differentially support chromatin structure, selectively affecting transcription and cell viability. METHODS: Using RNA-seq and BRD4 ChIP-seq, the differential effect of BETi treatment on the transcriptome and BRD4 chromatin occupancy of human aortic endothelial cells from diabetic patients (dHAECs) stimulated with TNFα was evaluated. Chromatin decondensation and DNA fragmentation was assessed by immunofluorescence imaging and quantification. Key dHAEC findings were verified in proliferating monocyte-like THP-1 cells using real time-PCR, BRD4 co-immunoprecipitation studies, western blots, proliferation and apoptosis assays. FINDINGS: We discovered that 1) BRD4 co-localizes with Ying-Yang 1 (YY1) at TADBs, critical chromatin structure complexes proximal to many DNA repair genes. 2) BD2-selective BETi enrich BRD4/YY1 associations, while pan-BETi do not. 3) Failure to support chromatin structures through BRD4/YY1 enrichment inhibits DNA repair gene transcription, which induces DNA damage responses, and causes widespread chromatin decondensation, DNA fragmentation, and apoptosis. 4) BD2-selective BETi maintain high order chromatin structure and cell viability, while reducing deleterious pro-inflammatory transcription. INTERPRETATION: BRD4 plays a previously unrecognized role at TADBs. BETi differentially impact TADB stability. Our results provide translational insight for the development of BETi as therapeutics for a range of diseases including CVD, chronic kidney disease, cancer, and COVID-19.