Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?

Pascolo, Lorella; Zito, Gabriella; Zupin, Luisa; Luppi, Stefania; Giolo, Elena; Martinelli, Monica; Rocco, Daniela De; Crovella, Sérgio; Ricci, Giuseppe

doi:10.3390/microorganisms8101492

Cited by 27 publications

(37 citation statements)

References 166 publications

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“…Brodin has discussed the immune-system differences between old and young people and men and women and other associated immunological factors towards the disease presentations and severity [172]. As per the previous studies, a disturbance in fertility in male patients is also expected due to the hormone-regulated expression of the ACE2 receptor [173]. However, the relationship between SARS-CoV-2 and renin-angiotensin system (RAS) in male reproductive apparatus is still unclear.…”

Section: Degree Of Difference In Cytokines Storm In Relation To Age Sex and Co-morbiditiesmentioning

confidence: 96%

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

et al. 2021

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The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

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Section: Degree Of Difference In Cytokines Storm In Relation To Age Sex and Co-morbiditiesmentioning

confidence: 96%

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

et al. 2021

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“…All available studies indicate that COVID-19 could influence male reproductive health and it is suggested that the effect of SARS-CoV-2 in the male reproductive system should be considered [ 13 ]. Accordingly, this study was designed to elucidate the impacts of SARS-CoV-2 on the male reproductive system by investigating damage of BTB and histological change in human testis.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 disrupts the blood–testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins

et al. 2021

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Objective Junctional proteins are the most important component of the blood-testis barrier and maintaining the integrity of this barrier is essential for spermatogenesis and male fertility. The present study elucidated the effect of SARS-CoV-2 infection on the blood–testis barrier (BTB) in patients who died from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications. Methods In this study, lung and testis tissue was collected from autopsies of COVID-19 positive ( n = 10) and negative men ( n = 10) and was taken for stereology, immunocytochemistry, and RNA extraction. Results Evaluation of the lung tissue showed that the SARS-CoV-2 infection caused extensive damage to the lung tissue and also increases inflammation in testicular tissue and destruction of the testicular blood barrier. Autopsied testicular specimens of COVID-19 showed that COVID-19 infection significantly changes the spatial arrangement of testicular cells and notably decreased the number of Sertoli cells. Moreover, the immunohistochemistry results showed a significant reduction in the protein expression of occluding, claudin-11, and connexin-43 in the COVID-19 group. In addition, we also observed a remarkable enhancement in protein expression of CD68 in the testes of the COVID-19 group in comparison with the control group. Furthermore, the result showed that the expression of TNF-α, IL1β, and IL6 was significantly increased in COVID-19 cases as well as the expression of occludin, claudin-11, and connexin-43 was decreased in COVID-19 cases. Conclusions Overall, the present study demonstrated that SARS-CoV-2 could induce the up-regulation of the pro-inflammatory cytokine and down-regulation of junctional proteins of the BTB, which can disrupt BTB and ultimately impair spermatogenesis.

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“…Coronaviruses are a family of positive-sense singlestranded RNA viruses that cause infections in birds and mammals as well as humans, inducing respiratory, hepatic, neurological and gastrointestinal diseases [1]. The novel coronavirus SARS-CoV-2 causes pneumonia, a severe acute respiratory disease .…”

Section: Introductionmentioning

confidence: 99%

Molecular diagnosis of SARS-CoV-2 in seminal fluid

Paoli

Pallotti

Nigro

et al. 2021

J Endocrinol Invest

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Purpose Due to relevant repercussions on reproductive medicine, we aimed to evaluate feasibility of RT-PCR as a detection method of SARS-CoV-2 RNA in seminal fluid. Methods A qualitative determination of the RT-PCR assays in semen was performed through different approaches: (1) efficiency of RNA extraction from sperm and seminal plasma was determined using PRM1 and PRM2 mRNA and a heterologous system as control; (2) samples obtained by diluting viral preparation from a SARS-CoV-2 panel (virus cultured in Vero E6 cell lines) were tested; (3) viral presence in different fractions of seminal fluid (whole sample, seminal plasma and post-centrifugation pellet) was evaluated. Semen samples from mild and recovered COVID-19 subjects were collected by patients referring to the Infectious Disease Department of the Policlinico Umberto I Hospital - “Sapienza” University of Rome. Control subjects were recruited at the Laboratory of Seminology-Sperm Bank “Loredana Gandini'' of the same hospital. Results The control panel using viral preparations diluted in saline and seminal fluid showed the capability to detect viral RNA presence with Ct values depending on the initial viral concentration. All tested semen samples were negative for SARS-CoV-2, regardless of the nasopharyngeal swab result or seminal fluid fraction. Conclusion These preliminary data show that RT-PCR for SARS-CoV-2 RNA testing appears to be a feasible method for the molecular diagnosis of SARS-CoV-2 in seminal fluid, supported by results of the control panel. The ability to detect SARS-CoV-2 in semen is extremely important for reproductive medicine, especially in assisted reproductive technology and sperm cryopreservation.

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Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?

Cited by 27 publications

References 166 publications

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

COVID-19 disrupts the blood–testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins

Molecular diagnosis of SARS-CoV-2 in seminal fluid

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