Herpes simplex virus inoculation in murine rete testis results in irreversible testicular damage

Малолина, Е. А.; Kulibin, A. Yu.; Naumenko, Victor; Гущина, Е. А.; Завалишина, Л Э; Кущ, А А

doi:10.1111/iep.12071

Cited by 19 publications

(13 citation statements)

References 19 publications

(32 reference statements)

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“…Antiviral treatment of infertile male patients positive for HSV in semen has resulted in successful pregnancies (El Borai et al ., ; Kotronias & Kapranos, ). In vitro and animal models of testicular HSV infection have shown virus‐induced disturbance of spermatogenesis followed by sterility (Naumenko et al ., , ; Malolina et al ., , ).…”

Section: Introductionmentioning

confidence: 97%

Detection and quantification of human herpes viruses types 4–6 in sperm samples of patients with fertility disorders and chronic inflammatory urogenital tract diseases

et al. 2014

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SUMMARYAcute and chronic infections of the seminal tract are among the most common causes of male infertility. As at least half of male infertility cases are classified as idiopathic, some of these cases might be attributed to asymptomatic infection. The detection and quantification of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpes virus type 6 (HHV-6) DNA in semen samples were performed. A total of 232 patients were divided into five groups: (i) infertile men with varicocoele; (ii) men with idiopathic infertility; (iii) infertile men with chronic inflammatory urogenital tract diseases (IUTD); (iv) fertile men with IUTD and (v) men whose partners had a history of pregnancy loss. In the study population, the prevalence of viral DNA was 17.7, 3.4% for EBV, 5.2% for CMV, 6.5% for HHV-6, 0.43% for EBV + CMV, 0.87% for EBV + HHV-6 and 1.3% for CMV + HHV-6. The median viral loads for EBV, CMV and HHV-6 were 500, 2250 and 250 copies/mL respectively. Of the sperm cell fractions, derived from infected samples 87.5% contained viral DNA. No association between EBV and fertility disorders or IUTD was found. CMV detection was much higher in the group of patients with infertility and concomitant IUTD compared with the other groups combined (18.5% vs. 5.4%, p = 0.03) and associated with reduced sperm cell count (39.5 9 10 6 /mL vs. 72.5 9 10 6 /mL, p = 0.036). Immunostaining of spermatozoa from infected samples and in vitro-infected cells detected CMV in sperm heads, tails and connecting pieces and revealed attachment to sperm membrane and intracellular localization. HHV-6 was the more common in fertile men with chronic IUTD than in the other groups combined (19% vs. 6.3%, p = 0.018) and had no effect on sperm parameters. The results suggest that both CMV and HHV-6 may contribute to the aetiology of IUTD and, moreover, CMV-associated IUTD can lead to male sterility.

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Section: Introductionmentioning

confidence: 97%

Detection and quantification of human herpes viruses types 4–6 in sperm samples of patients with fertility disorders and chronic inflammatory urogenital tract diseases

et al. 2014

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“…) and viral infections (Malolina et al. ) coincide with the fact that tubular involvement is a sequential process in which germinal epithelium disorganization and detachment, accompanied by an arrest in spermatogenesis, occur. Additionally, germinal epithelium thinning was obvious, and multinucleated germ cells and pyknotic cells appeared inside the tubular lumen.…”

Section: Discussionmentioning

confidence: 99%

Sequential testicular atrophy involves changes in cellular proliferation and apoptosis associated with variations in aromatase P450 expression levels in Irs‐2‐deficient mice

et al. 2018

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Insulin receptor substrate 2 (Irs‐2) is an intracellular protein susceptible to phosphorylation after activation of the insulin receptor. Its suppression affects testis development and its absence induces peripheral resistance to insulin. The aim of this study was to identify changes induced by the deletion of Irs‐2 in the testicular structure and by the altered expression of cytochrome P450 aromatase, a protein necessary for the development and maturation of germ cells. Adult knockout (KO) mice (Irs‐2−/−, 6 and 12 weeks old) and age‐matched wild‐type (WT) mice were used in this study. Immunohistochemistry and Western blot analyses were performed to study proliferation (PCNA), apoptosis (active caspase‐3) and P450 aromatase expression in testicular histological sections. Deletion of Irs‐2 decreased the number of epithelial cells in the seminiferous tubule and rete testis. Aberrant cells were frequently detected in the epithelia of Irs‐2−/− mice, accompanied by variations in spermatogonia, which were shown to exhibit small hyperchromatic nuclei as well as polynuclear and anuclear structures. The amount of cell proliferation was significantly lower in Irs‐2−/− mice than in WT mice, whereas apoptotic processes were more common in Irs‐2−/− mice. Aromatase P450 reactivity was higher in 6‐week‐old KO mice than in WT mice of the same age and was even higher at 12 weeks. Our results suggest that Irs‐2 is a key element in spermatogenesis because silencing Irs‐2 induces the sequential development of testicular atrophy. The effects are observed mainly in germ cells present in the seminiferous tubule, which may be due to changes in cytochrome P450 aromatase expression.

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“…HSV-2 can cause inflammatory disease of the genitourinary system of males, infects male sex cells, and is associated with poor sperm quality and decreased sperm concentration and motility. Finally, in a model of ascending urogenital HSV infection in mice, acute viral infection results in irreversible atrophy of the germinal epithelium, orchitis and infertility ( 35 , 36 ), but studies in natural hosts of herpesviruses are lacking.…”

Section: Introductionmentioning

confidence: 99%

Histopathologic Findings Following Experimental Equine Herpesvirus 1 Infection of Horses

et al. 2019

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Histopathological differences in horses infected with equine herpesvirus type 1 (EHV-1) of differing neuropathogenic potential [wild-type (Ab4), polymerase mutant (Ab4 N752), EHV-1/4 gD mutant (Ab4 gD4)] were evaluated to examine the impact of viral factors on clinical disease, tissue tropism and pathology. Three of 8 Ab4 infected horses developed Equine Herpesvirus Myeloencephalopathy (EHM) requiring euthanasia of 2 horses on day 9 post-infection. None of the other horses showed neurologic signs and all remaining animals were sacrificed 10 weeks post-infection. EHM horses had lymphohistiocytic vasculitis and lymphocytic infiltrates in the lungs, spinal cord, endometrium and eyes. EHV-1 antigen was detected within the eyes and spinal cord. In 3/6 of the remaining Ab4 infected horses, 4/9 Ab4 N752 infected horses, and 8/8 Ab4 gD4 infected horses, choroiditis was observed. All males had interstitial lymphoplasmacytic and/or histiocytic orchitis and EHV-1 antigen was detected. In conclusion, only animals sacrificed due to EHM developed overt vasculitis in the CNS and the eye. Mild choroiditis persisted in many animals and appeared to be more common in Ab4 gD4 infected animals. Finally, we report infiltrates and changes in the reproductive organs of all males associated with EHV-1 antigen. While the exact significance of these changes is unclear, these findings raise concern for long-term effects on reproduction and prolonged shedding of virus through semen.

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Herpes simplex virus inoculation in murine rete testis results in irreversible testicular damage

Cited by 19 publications

References 19 publications

Detection and quantification of human herpes viruses types 4–6 in sperm samples of patients with fertility disorders and chronic inflammatory urogenital tract diseases

Detection and quantification of human herpes viruses types 4–6 in sperm samples of patients with fertility disorders and chronic inflammatory urogenital tract diseases

Sequential testicular atrophy involves changes in cellular proliferation and apoptosis associated with variations in aromatase P450 expression levels in Irs‐2‐deficient mice

Histopathologic Findings Following Experimental Equine Herpesvirus 1 Infection of Horses

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