The role of Interleukin-4 in COVID-19 associated male infertility – A hypothesis

Renu, Kaviyarasi; Subramaniam, Mohana Devi; Chakraborty, Rituraj; Myakala, Haritha; Iyer, Mahalaxmi; Bharathi, G.; Kamalakannan, Siva; Vellingiri, Balachandar; Gopalakrishnan, Abilash Valsala

doi:10.1016/j.jri.2020.103213

Cited by 45 publications

(38 citation statements)

References 96 publications

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“…Therefore, based on these studies, it can be explained, how an increase in expression of inflammatory cytokines, including TNF-α, IL-1β and IL-6, has caused a decrease in BTB proteins expression including occludin, claudin-11 and connexin-43 in the COVID-19 group. Another study has reported that the levels of pro-inflammatory chemokines and cytokines, including IL-6, TNF-α, and MCP-1, play a noteworthy role in the immunopathology of SARS-CoV-2, in semen samples of COVID-19 patients increased [ 30 ]. However, one of the mechanisms underlying COVID-19-associated barrier disruption is increasing the susceptibility of testicular cells to interactions with other immune cells, leading to increased infiltration across the barrier 31).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Following this same line of thought, Renu et al demonstrated that while many carriers of the disease are asymptomatic, the deleterious reproductive effects in the infected man can be silent and, thus, make these conditions more serious due to a late diagnosis (Renu et al, 2020).…”

Section: Viral Infectionmentioning

confidence: 94%

“…The most serious cases of COVID-19 are accompanied by a high level of IL-6, with receptors expressed in testicular cells, which justifies male gonadal involvement and the appearance of orchitis as a complication of Sars-CoV-2 (Renu et al, 2020;Haghpanah et al, 2021).…”

Section: Physiopathologymentioning

confidence: 99%

Male infertility and COVID-19: Is there a relationship?

Goés

Araújo-Neto

Araújo

et al. 2021

RSD

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In the testicles, the expression of Angiotensin-Converting Enzyme 2 receptors makes it more susceptible to infection by Sars-CoV-2 and, therefore, to male infertility with significant health problems for the patient. Therefore, this study aimed to analyze the clinical pathophysiology and the mechanisms involved in the genesis of male infertility from COVID-19, through the critical analysis of the main scientific evidence on the subject presented so far. From an integrative review of the literature containing 30 studies selected using inclusion criteria in the period 2020-2021, the direct and indirect impacts on male fertility in pathophysiological and psychosocial terms were observed in this study, in addition to therapeutic options, guidelines host and efficient semiological approach. Thus, the impact of the pandemic, even after one year, is immeasurable. Additional studies to reveal the real consequences and the mechanism by which the disease can affect male fertility are still needed. It is essential to pay more attention to male genital exams in patients with COVID-19. The psychobiological consequences of the pandemic in infertile patients should not be underestimated.

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“…In COVID-19, T helper type 2 cells activate the IL-4 (through IgG and IgE) and mediate the apoptosis which may cause male infertility. On the other hand, IL-4 decreases the level of the ACE-2 which leads to male infertility in COVID-19 [ 82 ]. High level of IL-6S is observed in severe cases of COVID-19 and its receptors are highly expressed in testicular cells [ 83 ].…”

Section: Testicular Immunitymentioning

confidence: 99%

The probable destructive mechanisms behind COVID-19 on male reproduction system and fertility

Moshrefi

Ghasemi-Esmailabad

Ali

et al. 2021

J Assist Reprod Genet

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Purpose The present study aims to summarize the current understanding of probable mechanisms and claims of adverse effects of SARS-CoV-2 on male fertility potential. Methods Our search was including original articles, reviews, guidelines, letters to the editor, comments on guidelines, and editorials, regarding the male reproductive system. We used the words SARS-CoV-2, coronavirus, severe acute respiratory syndrome coronavirus 2, “2019 ncov,” testis, sperm, male factor infertility, fertility treatment, semen, assisted reproductive technology (ART), sexual transmission, and ACE2. Results Data showed coronavirus affects men more than women because of more expression of 2019 nCoV receptors (ACE2 and TMPRSS2) in testicular cells. Also, “Bioinformatics Analysis” suggests that sperm production may be damaged, since “Pseudo Time Analysis” has shown disruption in spermatogenesis. “Gene Ontology” (GO) showed an increase in viral reproduction and a decrease in sperm production-related terms. Recently, SARS-COV-2 mRNA and protein were detected in the semen of patients that had recovered from SARS-CoV-2 infection. Therefore, the probable disruption of blood-testis barrier (BTB) in febrile diseases is suspected in the acute phase of the disease enabling viral entry into the testes. Not only is spermatogenesis disturbed, but also disturbs gonadotropin, androgens, and testosterone secretion during SARS-CoV-2 infection. No sexual transmission has been reported yet; however, detection of the virus in semen still makes the sexual transmission an open question. Conclusion There is a concern that male fertility may be disturbed after the SARS-CoV-2 infection. Therefore, follow-up of the reproductive functions and male fertility may be necessary in recovered cases, especially in aged men.

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The role of Interleukin-4 in COVID-19 associated male infertility – A hypothesis

Cited by 45 publications

References 96 publications

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

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

Male infertility and COVID-19: Is there a relationship?

The probable destructive mechanisms behind COVID-19 on male reproduction system and fertility

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