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Mumps virus infection in adolescent males may cause infertility! Why?

Abstract

When someone talks about the Mumps virus, we all remember that time when the cheeks of the neighborhood playmates became painfully puffed up like puffy fish – following an inflammatory response that culminated in the swelling of the parotid glands – Mumps parotitis. However, one of the distinctive features of mumps infection is its potential to invade the testes, resulting in orchitis (inflammation of the testes). Notably, this testicular involvement is most observed in post-pubertal males, specifically around the age of twelve. This article explores the underlying scientific factors contributing to the preferential targeting of the testes by the mumps virus during adolescence.

Introduction:

Mumps, a highly contagious viral infection caused by the mumps virus, has been recognized since ancient times. The virus typically spreads through respiratory droplets and primarily affects the salivary glands, leading to parotitis. However, one of the complications associated with mumps is orchitis, which is characterized by inflammation of one or both testes. Surprisingly, testicular involvement primarily occurs during puberty, with a peak incidence around the age of twelve. Why? We will explain this enigmatic phenomenon in the subsequent paragraphs.

Immune Privilege of the Testes:

The testes possess a unique immunological environment, often referred to as immune privilege, which allows them to maintain spermatogenesis (formation of sperms) while minimizing immune-mediated damage. The immune privilege is primarily attributed to the blood-testis barrier (BTB), which physically separates the developing germ cells from the immune system. This barrier prevents immune cells, including lymphocytes and antibodies, from freely accessing the seminiferous tubules, where spermatogenesis occurs. During puberty, the BTB undergoes restructuring to accommodate the maturation of sperm cells. This temporary weakening of the BTB might provide an opportunity for the mumps virus to breach the barrier and invade the testes.

Expression of Mumps Virus Receptors:

Viruses must first bind to specific receptors on the host cell surface to successfully infect a target cell. The mumps virus utilizes the sialic acid residues present on cell surface glycoproteins as entry receptors. Notably, the testicular tissues, including the seminiferous tubules, exhibit high levels of the sialic acid receptor, rendering them susceptible to mumps virus infection. The enhanced expression of these receptors during puberty may facilitate viral attachment and entry into the testicular cells, leading to orchitis.

Hormonal Factors:

Puberty is a critical period characterized by significant hormonal changes, including increased luteinizing hormone (LH) and testosterone secretion. Testosterone plays a crucial role in the maturation and maintenance of the male reproductive system. Interestingly, studies have shown that testosterone levels are positively correlated with mumps virus replication and the severity of orchitis. The exact mechanisms underlying this relationship are not yet fully understood. However, it is plausible that the increased testosterone levels during puberty enhance viral replication and promote the development of testicular inflammation.

Host Immune Response:

The immune response plays a crucial role in the outcome of viral infections. Notably, the immune response mounted against the mumps virus in the testes may contribute to the development of orchitis. It is postulated that the immune response to the mumps virus may induce a local inflammatory cascade, causing damage to the testicular tissues. Furthermore, the presence of autoimmunity against testicular antigens triggered by the viral infection may also contribute to the testicular inflammation observed during mumps orchitis.

Conclusion:

The preferential targeting of the testes by the mumps virus during puberty, resulting in orchitis, involves a combination of factors. The unique immunological characteristics of the testes, including the transient weakening of the BTB, the expression of virus receptors, hormonal changes during puberty, and the host immune response, collectively contribute to the susceptibility of the testes to infection. Further research is needed to elucidate the intricate interplay between these factors and develop strategies for prevention and treatment of mumps orchitis. Now, you should have your boy-child vaccinated against the Mumps virus.

IAmDrSsekandi

MBChB (MUK), Graduate Fellow, Department of Physiology, Makerere University Founder and Content Creator Peer reviewer, Associate Editor

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