Muhsin J. M, Yousif S. O, Hadi A. M, Hamad M. H. Male Infertility and Viral Infection: Interference Role of the Human Herpesvirus Types (3 – 6) With Disturbances Effects of Some Cytokines Hypersecretion and Seminal Oxidative Defense System in the Infertility Etiopathogenesis of Some Idiopathic Infertile Iraqi Patients. Biomed Pharmacol J 2019;12(3).
Manuscript received on :4-Jun-2019
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Published online on: 16-09-2019
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Jasim Mohammed Muhsin1, Sura O. Yousif2, Ameer M. Hadi3 and Mohammed Haider Hamad4

1Health and Medical Technology College -Middle Technical University - Baghdad - Iraq.

2Technical Institute-Suwaira - Middle Technical University - Wasit - Iraq.

3DNA Research Center -Babylon University - Babylon - Iraq.

4College of Al Mustaqbal University.

Corresponding Author E-mail: jasim.muhsin99@gmail.com

DOI : https://dx.doi.org/10.13005/bpj/1747

Abstract

To study the role of potential relationship of chronic human herpes virus types (3 – 6) infection and their correlation with the up-regulation of some cytokines (IL-2, IL-10 and IFN gamma) and effect of (8-OHdG) and (TAOC) levels onto male infertility. A Case – control study with semen samples which were collected by masturbation during the routine semen analysis of a total ninety age-matched participants as; fertile males 35 (38.9%) with proven fertility as a normal semen quality and infertile males 55 (61.1%) with at least one year of infertility and poor semen quality. All semen biomarkers of Human herpes viruses (HHVs): Varicella zoster virus (VZV-IgG), Epstein-Barr virus (EBV-IgG), Cytomegalovirus (CMV-IgG), Human herpes virus type 6 (HHV6-IgG), Interlukin-2 (IL-2), Interlukin-10 (IL-10), Interferon-gamma (IFN-γ), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and Total Antioxidant Capacity (TAOC) which were included in the study had been estimated by quantitative ELISA based method and the correlations with sperms parameters were evaluated. The main significant outcomes in this study of the infertile males group 55 (61.1%) were: high percentages of seminal IgG; N (%; Mean±SD) were detected of HHV6, 48 (53.3%;1.26± 0.51) then CMV, 39 (43.3%;1.51± 0.95) followed by EBV, 34 (37.8%; 2.20±1.47), and the highest abnormal cytokines levels were estimated in; 44 (48.9%; 112.62±38.64) and 40 (44.4%; 22.75±10.65) for IFN-γ and IL-10 respectively. Furthermore, High 8-OHdG level was detected in 47 (52.2%;7.29±2.15) and very low level of TAOC was detected in 16 (17.8%;19.34±12.17). Significant negative correlation between semen biomarkers and standard sperms parameters was found which were represented by: 45 (50.0%) of total sperms count less than (33 million ml), 52 (57.8%) of progressive motile sperms less than (31%). Finally, about 33 (24.4%) of abnormal sperm morphology was detected. Our results hypothesized that chronic asymptomatic viral infection with increasing of cytokines concentrations consequently disturbance the semen oxidative status, antioxidant defense systems that induce sperms DNA damage then might be collectively act as a co-factors on the etiology of the male infertility.

Keywords

Antioxidant Status; Cytokines; Human Herpes Virus; Infertility; Oxidative Stress

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Muhsin J. M, Yousif S. O, Hadi A. M, Hamad M. H. Male Infertility and Viral Infection: Interference Role of the Human Herpesvirus Types (3 – 6) With Disturbances Effects of Some Cytokines Hypersecretion and Seminal Oxidative Defense System in the Infertility Etiopathogenesis of Some Idiopathic Infertile Iraqi Patients. Biomed Pharmacol J 2019;12(3).

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Muhsin J. M, Yousif S. O, Hadi A. M, Hamad M. H. Male Infertility and Viral Infection: Interference Role of the Human Herpesvirus Types (3 – 6) With Disturbances Effects of Some Cytokines Hypersecretion and Seminal Oxidative Defense System in the Infertility Etiopathogenesis of Some Idiopathic Infertile Iraqi Patients. Biomed Pharmacol J 2019;12(3). Available from: http://biomedpharmajournal.org/?p=28482

Introduction

Male infertility is a multifactorial challenging with a big concern and a significant clinical problems worldwide, which affects about (8–12%) of partners globally. “Male factor” take about a fifty percent of all infertility cases, which exhibit abnormal sperm parameters in about two percent of them which represented by; low sperm concentration, changing of semen pH, poor progressive sperms motility, abnormal morphology, defect of vitality or a combination of them or even failure to produce sperms and erectile dysfunction. Even more the average of infertility cases in less developed countries are higher and it noticed that infectious diseases were took a huge percentage of these cases [1]. Additionally, most of acute or chronic infections in the seminal tract are among the most communal reasons of male infertility. Besides, some of the infertile cases had been with asymptomatic infection and about a fifty percent of infertility cases are idiopathic [2].

Human herpes viruses (HHVs) are a common sexually transmissible viruses with possible effect on male infertility factor either directly by the viral toxic effect onto genital tract cells or indirectly by local or systemic infectious or immunological responses. So that, (EBV), (CMV) and (HHV-6) of herpesviradae family are commonly found in semen, but the influence of these viral agents on male fertility has not been broadly explored. Several studies have estimated the CMV prevalence in about (0 – 62.5%) of human semen samples in a many countries [3]. Another study determined the incidence of viral DNA was 3.4% for EBV, 5.2% for CMV, 6.5% for HHV-6 with different values for viral co-infection among them [2].  Few studies had examined the existence of VZV in semen samples of infertile men, so it had been indicated that the male genital tract may act as a reservoir for variable infectious agents [4]. Despite of these significant outcomes still the main role of HHVs in male infertility unexplained clearly.

Furthermore, cytokines are regulatory proteins involved in multiple immune responses with controversial effects onto testicular cells functions which are physiologically produced up there. And, there is compelling evidence that most of cytokines, play a significant regulatory role in the testis development and normal function of the testicular cells. Pro-inflammatory cytokines such as IL-2 and IFN-γ have direct effects on differentiation of spermatogenic cell, testicular steroidogenesis and spermatogenesis while anti-inflammatory cytokines such as IL-10 also associated with testicular development. Thus, dysregulation of cytokine expression during infection or illness may participate into the disruption of testicular function and effect on male fertility [5,6]

Moreover, oxidative stress is a significant factor and effects on the rates of male fertility. High seminal Reactive Oxygen Species (ROS) concentration in semen can effect on the antioxidant defense system of total antioxidant capacity (TAOC) in seminal plasma and spermatozoa to produce oxidative stress and may influences on sperm function. Many studies proposed that ROS interfere with DNA sperms integrity, therefore, sperm DNA damage is closely associated with male infertility as 8-hydroxy-2′-deoxyguanosine (8-OHdG) which was considered a sensitive indicator of oxidative sperms DNA damage caused by ROS in human semen samples [7-9].

Therefore, the aims of this study were to provide a knowledge about the interferences of some human herpes viruses (HHVs) as chronic infection or with reactivation cycle and up-regulation of some cytokines expression in accordance with uncontrolled oxidative stress which maybe collectively act as a co-factors in the causes of infertility in a randomized asymptomatic infertile males.

Material and methods

Participants and sampling 

Seminal fluid samples were collected from ninety volunteers who were attending Kamal El-Samurai Hospital (Baghdad) from November 2018 to February 2019, (aged 23 – 44): consisting of (n=35; 38.9%) healthy controls who were experienced the fatherhood and (n=55; 61.1%) infertile patients with primary infertility (had no baby after one year of unprotected intercourse; idiopathic i

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