SARS-CoV-2-induced cytokine storm drives prolonged testicular injury and functional impairment in mice that are mitigated by dexamethasone

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012804 - e1012804

Published: Jan. 7, 2025

Compromised male reproductive health, including reduced testosterone and sperm count, is one of the long COVID symptoms in individuals recovering from mild-severe disease. COVID-19 patients display testicular injury acute stage altered serum fertility markers recovery phase, however, long-term implications on testis remain unknown. This study characterized consequences SARS-CoV-2 function. The K18-hACE2 mice that survived infection were followed for month after function assessed at different stages recovery. impact key testes function-related hormones was measured. efficacy inflammation-suppressing drug preventing also evaluated. morphological defects like sloughing spermatids into lumen increased apoptotic cells sustained 2–4 weeks correlated with inflammation immune cell infiltration. Transcriptomic analysis revealed dysregulation inflammatory, death, steroidogenic pathways. Furthermore, levels associated a transient reduction count fertility. Most impairments resolved within infection. Importantly, dexamethasone treatment attenuated damage, inflammation, Our results implicate virus-induced cytokine storm as major driver functional impairments, timely prevention which limits damage. These findings serve model evaluating therapeutics may guide clinical strategies to improve health outcomes post-SARS-CoV-2

Language: Английский

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Impact of COVID-19 on testicular function: a systematic review and meta-analysis

Endocrine, Journal Year: 2024, Volume and Issue: 85(1), P. 44 - 66

Published: Feb. 12, 2024

Studies investigating the effects of SARS-CoV-2 on male reproductive function are few and heterogeneous, results often conflicting. This systematic review meta-analysis was carried out studies conducted in men with active or anamnestic infection to evaluate its consequences sex hormone profile semen parameters.

Language: Английский

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The Aftermath of COVID-19: Exploring the Long-Term Effects on Organ Systems

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 913 - 913

Published: April 20, 2024

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions people all over the world. Previous studies have shown PASC impacts 10% infected patients which 50–70% are hospitalised. It has also been 10–12% those vaccinated against COVID-19 were affected by and its complications. The severity later development symptoms positively associated with early intensity infection. Results: generated health complications caused involve vast variety organ systems. Patients diagnosed neuropsychiatric neurological symptoms. cardiovascular system involved several diseases such as myocarditis, pericarditis, coronary artery reported. Chronic hematological problems thrombotic endothelialitis hypercoagulability described conditions could increase risk clotting disorders coagulopathy in patients. Chest pain, breathlessness, cough respiratory long-COVID causing distress syndrome. observed immune notable, involving diseases. renal was impacted, resulted raising issues, fibrosis, sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, male infertility. Symptoms diarrhea, nausea, loss appetite, taste among reported observations due gastrointestinal disorders. Skin abnormalities might be an indication long-term implications persistent cutaneous complaints linked PASC. Conclusions: Long-COVID multidimensional syndrome considerable public implications, affecting physiological systems demanding thorough medical therapy, more study address underlying causes effects needed.

Language: Английский

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COVID-19 associates with semen inflammation and sperm quality impairment that reverses in the short term after disease recovery

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: July 11, 2023

Introduction: COVID-19 exerts deleterious effects on the respiratory, cardiovascular, gastrointestinal, and central nervous systems, causing more severe disease in men than women. However, cumulative reported data about putative consequences male reproductive tract fertility are controversial. Furthermore, long-term of SARS-CoV-2 infection still uncertain. Methods: In this study, we prospectively evaluated levels inflammatory cytokines leukocytes semen sperm quality parameters a cohort 231 reproductive-aged patients, unvaccinated, who had recovered from mild or 62 healthy control individuals. Sperm was assessed early (less 3 months) long (more up to 6 after having COVID-19. Interestingly, unlike most studies, available extensive background baseline patients' allowed performing accurate analysis quality. Results: Significantly higher IL-1β, TNF IFNγ were detected patients recently and/or with respect individuals indicating inflammation. Moreover, showed significantly reduced volume, lower total counts, impaired motility viability. all observed alterations returned values months recovery. Discussion: These results indicate that associates inflammation disease. seems not include detrimental potential since reversible 1-2 spermatogenesis cycles. constitute compelling evidence allowing better understanding associated sequelae, fundamental for collection assisted reproduction.

Language: Английский

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pH Homeodynamics and Male Fertility: A Coordinated Regulation of Acid-Based Balance during Sperm Journey to Fertilization

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 685 - 685

Published: June 12, 2024

pH homeostasis is crucial for spermatogenesis, sperm maturation, physiological function, and fertilization in mammals. HCO3− H+ are the most significant factors involved regulating male reproductive system. Multiple pH-regulating transporters ion channels localize testis, epididymis, spermatozoa, such as (solute carrier family 4 solute 26 transporters), carbonic anhydrases, H+-transport enzymes (e.g., Na+-H+ exchangers, monocarboxylate transporters, H+-ATPases, voltage-gated proton channels). Hormone-mediated signals impose an influence on production of some or NBCe1, SLC4A2, MCT4, etc. Additionally, including sperm-specific cationic Ca2+ (CatSper) K+ (SLO3) directly indirectly regulated by pH, exerting specific actions spermatozoa. The slightly alkaline testicular conducive to whereas epididymis’s low concentration acidic lumen favorable maturation storage. Spermatozoa increases substantially after being fused with seminal fluid enhance motility. In female tract, subjected increasing concentrations uterine fallopian tube, causing a rise intracellular (pHi) leading hyperpolarization plasma membranes, capacitation, hyperactivation, acrosome reaction, ultimately fertilization. regulation initiated SLC26A3, SLC26A8, NHA1, sNHE, CFTR localized proven certain be fertility. This review intends present key characteristics pHi testes, efferent duct, fluid, well associated mechanisms during journey fertilization, proposing insights into outstanding subjects future research trends.

Language: Английский

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Single-cell transcriptome-wide Mendelian randomization and colocalization reveals immune-mediated regulatory mechanisms and drug targets for COVID-19

EBioMedicine, Journal Year: 2025, Volume and Issue: 113, P. 105596 - 105596

Published: Feb. 10, 2025

Language: Английский

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The Epididymis as a Target for Toxicants

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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The Aftermath of COVID-19: Exploring Long-Term Effects on the Organ Systems

Published: April 3, 2024

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions people all over the world. Previous studies have shown PASC impacts 10% infected patients which 50-70% are hospitalized. It has also been 10-12% those vaccinated against COVID-19 were affected with and its complications. The severity later development symptoms positively associated early intensity infection. Results: generated health complications caused by involve vast variety organ systems. Patients diagnosed neuropsychiatric neurological symptoms. Cardiovascular system involved several diseases such as myocarditis, pericarditis, coronary artery reported. Chronic hematological problems thrombotic endothelialitis hypercoagulability described condition could increase risk clotting disorders coagulopathy in patients. Chest pain, breathlessness, cough respiratory long causing distress syndrome. observed immune notable, involving diseases. Renal was impacted result raising issues, fibrosis, sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, male infertility. Symptoms diarrhea, nausea, loss appetite taste among reported observations due gastrointestinal disorders. Skin abnormalities might be an indication long-term implications persistent cutaneous complaints linked PASC. Conclusions: Long COVID multidimensional syndrome considerable public implications, affecting physiological systems demanding thorough medical therapy well more study address underlying causes effects.

Language: Английский

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Unlocking Genetic Mysteries during the Epic Sperm Journey toward Fertilization: Further Expanding Cre Mouse Lines

Biomolecules, Journal Year: 2024, Volume and Issue: 14(5), P. 529 - 529

Published: April 28, 2024

The spatiotemporal expression patterns of genes are crucial for maintaining normal physiological functions in animals. Conditional gene knockout using the cyclization recombination enzyme (Cre)/locus crossover P1 (Cre/LoxP) strategy has been extensively employed functional assays at specific tissue or developmental stages. This approach aids uncovering associations between phenotypes and regulation while minimizing interference among distinct tissues. Various Cre-engineered mouse models have utilized male reproductive system, including Dppa3-MERCre primordial germ cells, Ddx4-Cre Stra8-Cre spermatogonia, Prm1-Cre Acrv1-iCre haploid spermatids, Cyp17a1-iCre Leydig cell, Sox9-Cre Sertoli Lcn5/8/9-Cre differentiated segments epididymis. Notably, specificity functioning stage Cre recombinases vary, efficiency driven by depends on endogenous promoters with different sequences as well constructed vectors, even when controlled an identical promoter. generated via traditional CRISPR/Cas9 also exhibit properties. review focuses applied to Cre-targeting strategies, model screening, practical challenges encountered, particularly novel strains over past decade. It aims provide valuable references studies conducted system.

Language: Английский

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Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: May 22, 2024

SARS-CoV-2 is the causative virus of devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts therapeutic interventions, fight against continues as rapid emergence different variants concern increasing challenge long COVID-19, raising a vast demand to understand pathomechanisms its long-term sequelae develop strategies beyond per se . Notably, addition itself, replication cycle clinical severity also governed by host factors. In this review, we therefore comprehensively overview pathogenesis from perspective factors host-virus interactions. We sequentially outline pathological implications molecular interactions between multi-organ multi-system summarize current agents targeting for treating these diseases. This knowledge would be key identification new pathophysiological aspects mechanisms, development actionable targets tackling sequelae.

Language: Английский

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