Abstract:Low testicular volume (TV) is associated with a decreased testicular function. Several studies explored the conventional sperm parameters and the endocrine function in patients with low TV. No other parameters have been examined. On the basis of these premises, the aim of this study was to evaluate a non-conventional seminal parameter: seminal lymphocyte characterisation in men with low TV compared with that of subjects with normal TV. A further comparison was made between fertile men and infertile patients wi… Show more
“…The systematic immunohistochemical analysis of testis biopsies from infertile patients with azoospermia indicated that immune cells were mainly infiltrated by CD3 + T cells, instead of CD20 + B cells and CD11c+ dendritic cells, regardless of the degree of inflammation [25]. In patients with a low testicular volume, a positive linear relationship was observed between CD45 lymphocytes infiltration and sperm parameters, such as the percentage of immature germ elements, phosphatidylserine externalization, early apoptosis, and abnormal morphology [26]. In a systematic re-examination of tissue samples obtained from chronic orchitis with infertility, the infiltration of T lymphocytes was recorded in as many as 56.3% of cases [27].…”
The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literature on different T subtypes (regulatory T cells, helper T cells, cytotoxic T cells, γδ T cells, and natural killer T cells) in human and animal testes that support their regulatory roles in infertility and the orchitis pathology. While many in vitro studies have indicated the regulation potential of functional T cell subsets and their possible interaction with Sertoli cells, Leydig cells, and spermatogenesis, both under physiological and pathological processes, there have been no in situ studies to date. Nevertheless, the normal distribution and function of T cell subsets are essential for the immune privilege of the testes and intact spermatogenesis, and T cell-mediated immune response drives testicular inflammation. The distinct function of different T cell subsets in testicular homeostasis and the orchitis pathology suggests a considerable potential of targeting specific T cell subsets for therapies targeting chronic orchitis and immune infertility.
“…The systematic immunohistochemical analysis of testis biopsies from infertile patients with azoospermia indicated that immune cells were mainly infiltrated by CD3 + T cells, instead of CD20 + B cells and CD11c+ dendritic cells, regardless of the degree of inflammation [25]. In patients with a low testicular volume, a positive linear relationship was observed between CD45 lymphocytes infiltration and sperm parameters, such as the percentage of immature germ elements, phosphatidylserine externalization, early apoptosis, and abnormal morphology [26]. In a systematic re-examination of tissue samples obtained from chronic orchitis with infertility, the infiltration of T lymphocytes was recorded in as many as 56.3% of cases [27].…”
The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literature on different T subtypes (regulatory T cells, helper T cells, cytotoxic T cells, γδ T cells, and natural killer T cells) in human and animal testes that support their regulatory roles in infertility and the orchitis pathology. While many in vitro studies have indicated the regulation potential of functional T cell subsets and their possible interaction with Sertoli cells, Leydig cells, and spermatogenesis, both under physiological and pathological processes, there have been no in situ studies to date. Nevertheless, the normal distribution and function of T cell subsets are essential for the immune privilege of the testes and intact spermatogenesis, and T cell-mediated immune response drives testicular inflammation. The distinct function of different T cell subsets in testicular homeostasis and the orchitis pathology suggests a considerable potential of targeting specific T cell subsets for therapies targeting chronic orchitis and immune infertility.
“…Infiltration of CD45+ cells were observed in the chronically infected immunosuppressed pigs. CD45+ lymphocyte infiltration is directly associated with abnormal sperm morphology and early apoptosis of the sperm cells (51,52). Infiltration of CD45 in HEV infected mice testis has been attributed to the breakage of the BTB caused by HEV infection (15).…”
Hepatitis E virus (HEV) is an expanding zoonotic viral disease threat. Although HEV causes acute viral hepatitis, it is increasingly being recognized as a systemic pathogen with detection and damage in extrahepatic tissues. The presence of HEV RNA in the semen of chronically infected human patients in the absence of viremia and fecal shedding and presence of HEV in the sperm head underscores the need to understand the interaction of HEV within the male reproduction system. Male accessory glands secrete biofluids necessary for sperm nourishment and to neutralize the acidity of the vagina. The role of male accessory glands in the dissemination and persistence of HEV infection have not been studied. Using an immunosuppressed pig model for chronic HEV infection, we demonstrate infectious HEV in mature sperm cells altering the sperm motility and morphology. HEV isolated from sperm cells remained infectious in human hepatoma cells. Spermatic fluid contained lower virus titers than the sperm cells from chronically infected pigs highlighting that the sperm cells themselves can associate with the virus. Evaluation of the male accessory glands demonstrated viral replication, infiltration of CD45 leukocytes, and apoptosis associated with HEV infection. A decrease in serum testosterone levels was evident in the HEV infected pigs. Even though a lower viral RNA titer was seen in serum and feces of chronically infected, immunosuppressed and ribavirin treated pigs, high viral RNA and infectious particles in sperm is a concern. Our findings necessitate further studies defining the mechanism of sperm cell invasion by HEV, length of HEV survival in sperm cells during chronic HEV infection, and risk of sexual transmission of HEV during both acute and chronic phases of infection.Author SummaryHepatitis E virus, a leading cause of acute viral hepatitis, causes both acute and chronic infection in humans. Recent advances within the HEV field have demonstrated extrahepatic diseases associated with HEV. More recent findings have revealed infectious HEV in the vagina, Sertoli cells, and ejaculate of humans, and sperm cells of pigs. We demonstrate that the male accessory sex glands may have a role in the persistence of HEV infection during chronic infections. We utilized an established immunosuppressed pig model and treated pigs with ribavirin to study the presence of virus in the sperm cells. We demonstrated high viral RNA loads and infectious particles associated with sperm cells. Our study further highlights the importance of the testis, as an immune privileged site, in the maintenance of chronic HEV infection. New studies to evaluate the mechanisms by which HEV associates with sperm cells, the length of HEV survival in sperm cell fractions, and consideration of the testes as a potential HEV reservoir are necessary.
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