Chemical Biology Letters <p>The Chemical Biology Letters publishes research advances in field of Medicinal Chemistry, Chemistry Biology Interface research, Chemical Biology, Biochemistry, Drug design, development and clincal application advances.</p> ScineceIn Publishing en-US Chemical Biology Letters 2347-9825 <p>The submitting authors confirms the transfer of copyright to the ScienceIn for the contents (including graphics and associated media) and understand the all authors agrees to the statement of copyright transfer as submission is being made with the consent of all authors.</p> Reproductive tract infection, inflammation and male infertility <p>Infection or inflammation in the reproductive tract either via pathogenic intrusion or systemic diseases, reportedly are closely associated with deterioration in male fertility parameters. There are various proposed mechanisms to explain how reproductive tract infection or inflammation may curb male fecundity. One of the prominent mechanisms is via the over‐production of reactive oxygen species (ROS) inducing testicular oxidative stress (OS). In normal conditions, testicular cells produce ROS at modest levels to maintain physiological<br />functions. However, in inflammatory state, the surge of pro‐inflammatory mediators, cytokines lead to infiltration of immune cells (as observed by increased seminal leukocytes number) and these leukocytes serve as major contributors in the increased seminal plasma ROS levels that overwhelm the testicular antioxidant capacities. This initiates oxidative damage to the testicular cells to impair sperm production, as well as sperm membrane damage, disruption of essential signalling cascades, sperm mitochondrial and nuclear DNA damage and thereby impairing overall sperm functions. There are number of studies reporting diversified hypothesis of infection/inflammation‐induced male reproductive problems. This article aims to review the available information and present a precise overview of possible mechanisms relating male reproductive tract inflammation and male infertility.</p> Pallav Sengupta Sulagna Dutta Ahmed T Alahmar Urban John Arnold D’souza Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 75 84 Current perspectives of Male Infertility induced by Immunomodulation due to Reproductive Tract Infections <p>Globally, approximately 15% of couples of reproductive ages suffer from reproductive sterility. Almost half of such cases involve male sterility which is normally an asymptomatic condition, and, in most cases, the condition is reversible with proper treatment. Uropathogens and ascending sexually transmitted infections (STIs) are recognised as one among many other causes of inflammatory diseases of male genital tract which in turn are common reason of male infertility. Thus, any suspicion of inflammatory infection of the male genital tract should be immediately diagnosed Followed by further clinical evaluation in order to rule out any pathogenic situation due to infection of male genital tract which can lead to male sterility. Proper recognition and timely treatment can help to overcome such problem.</p> Suvendu Ghosh Debosree Ghosh Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 85 91 Obesity, systemic inflammation and male infertility <p>Studies in the last few decades have explained the role of different factors in the induction of obesity and related complications, such as obesity-induced male infertility. Among these factors, the endocrine and inflammatory factors are the major contributors that lead to male reproductive issues in obese men. However, the exact mechanism by which obesity-induced systemic inflammation or endocrine disruption may affect testicular functions or semen parameters remains elusive. The obesogenic physiological environment drives immune responses towards TH-1 cells-dominated chronic inflammatory process, which adversely affects all the major organs including the testes, epididymis, and male accessory glands. The pro-inflammatory mediators including the cytokines interfere with the intricate reproductive regulations by the hypothalamic-pituitary-gonadal/testicular (HPG/HPT) axis and thereby affect testicular functions. Most prominently, impaired steroidogenesis and spermatogenesis lead to hypogonadotropic hypogonadism and poor semen parameters. Moreover, the inflammatory responses may stimulate the overproduction of reactive oxygen species (ROS) establishing testicular oxidative stress (OS), which in turn may cause hormonal haywire as well as direct damage to the spermatozoa including sperm membrane damage, mitochondrial and nuclear DNA fragmentation and epigenetic modifications. This article aims to review the updated literature and depict a concise concept on the association of obesity and male infertility through the incurrence of systemic inflammatory processes.</p> Koushik Bhattacharya Pallav Sengupta Sulagna Dutta Ivan Rolland Karkada Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 92 98 Inflammation and Ageing: Probable role in Male infertility <p>A close association between male reproductive tract infection and inflammation with male infertility has been observed in close prominence. Male reproductive tract infection may arise due to various reasons, leading to inflammation with release of inflammatory mediators. Interactions among the mediators with other regulators affect sperm function and in addition, oxidative stress may develop owing to altered spermatogenesis and steroidogenesis. An increased inflammatory condition is observed on advancement of age in males and the incidence of inflammation in male reproductive tract may vary greatly among elderly men. Ageing is a pro-inflammatory condition which give rise to mitochondrial damage, oxidative stress, immunosenescence, endocrinosenescence, finally leading to impairment of the normal sperm function. The study about impact of inflammation on ageing and further its impact on male health draws great significance due to its role as a predictor of pathogenesis in relation to male infertility as well as on overall adverse male health outcome.</p> Silpi Acharyya Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 99 112 Role of toll-like receptors in the reproductive tract inflammation and male infertility <p>Male reproductive system is immunoprivileged and has special immune microenvironment to protect the testicular cells including the germ cells. A wide range of microorganisms are identified that can infect male reproductive tissues via hematogenous dissemination as well as male genitourinary tract, and severely impair reproductive functions. Testis is equipped with unique innate immune system to overcome its immunoprivileged state in case of testicular microbial infection. The testicular cells, mainly the Leydig cells, Sertoli cells and germ cells reportedly express components of innate immune system and their counteracting regulatory system. The innate immune responses are mostly mediated by pattern recognition receptors (PRRs), among which the toll-like receptors (TLRs) have crucial role in the testis. Various TLRs have been shown to express in the testicular cells, especially in Leydig and Sertoli cells and initiate appropriate innate immune responses. If the intricate balance of immune responsiveness and suppression in the testicular tissue is disrupted, it may result in inflammation which is an essential etiological factor of male infertility. Since the concept on the association of TLRs with male infertility is unclear, the present review article aims to synthesize a concise overview on the expression, functions and signalling pathways of testicular TLRs and their impact upon male fertility.</p> Sulagna Dutta Pallav Sengupta Muhjah Falah Hassan Anupam Biswas Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 113 123 Role of leucocytes in reproductive tract infections and male infertility <p>Oxidative stress (OS), occurring as a result of redox imbalance, have been considered a leading cause of male infertility. Redox imbalance is mediated by excessive production of reactive oxygen species (ROS) exceeding the antioxidant capacity. In seminal plasma, the main contributor of ROS are the infiltrated and resident leukocytes, although modest seminal levels of ROS are always maintained by spermatozoa and other testicular cells. Leukocytes are common constituents of seminal plasma even in healthy and fertile men. However, it has been suggested that during an inflammatory process the number of seminal leucocytes increases and activated leading to leukocytospermia. It is usually associated with reproductive tract infections, and subsequently, its impact on male infertility should not be overlooked. In such condition, leukocyte mediated ROS production and induction of OS can significantly deteriorate sperm morphology and functions through lipid peroxidation. This chain of oxidative damage disrupts the sperm membrane, intracellular components, as well as damages sperm nuclear and mitochondrial DNA. These may account for reduced semen quality and lead to male infertility, although further detailed interventions are needed to draw conclusive remark on the association of seminal leukocytes with male infertility. Thus, the present review article aims to provide a precise overview of the exact roles and sources of seminal leukocytes, the mechanism by which they operate during an inflammatory and healthy microenvironment and their association with male infertility</p> Ooi Chai Theam Sulagna Dutta Pallav Sengupta Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 124 130 Cytokines and adipokines in the regulation of spermatogenesis and semen quality <p>Male reproductive tract inflammation/infection possibly has a direct association with the occurrence of male infertility. Semen quality has been reported to be markedly reduced in conditions of male reproductive tract inflammation owing to functional or anatomical alterations in the reproductive tract such as accessory glands dysfunctions, obstructions in sperm transport, or spermatogenic disruptions by the inflammatory microenvironment. The severity of the inflammatory process and the level of impairment in male reproductive functions are associated with the roles played by individual inflammatory mediators, prominently the cytokines, adipokines and the reactive oxygen species (ROS). The mutual interactions of these biologically active substances originating mostly from the activated seminal leukocytes adversely affect testicular functions and deteriorate semen quality. However, several aspects regarding the association of inflammation, pro-inflammatory mediators and male infertility need to be clarified. Thus, the current review aims to present the roles of cytokines and adipokines in the context of understanding the mechanisms of inflammation-induced alterations in semen quality.</p> Tulay Irez Sermin Bicer Elif Sahin Sulagna Dutta Pallav Sengupta Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 131 139 Role of Epigenetic Changes in Reproductive Inflammation and Male Infertility <p>Male infertility is a public health problem affecting one in twenty couples globally. This multifactorial reproductive health issue is a consequence of testicular failure, ejaculatory dysfunction, and altered sperm characteristics caused by a combination of (epi) genetic, environmental, and lifestyle factors. Abnormal epigenetic changes have been proposed as an important causative factor for infertility in men. Abnormal DNA methylation, histone modification, altered non-coding RNAs have been well documented as in pathological conditions such as oligospermia, azoospermia, asthenospermia and tetratospermia in males. Additionally, chronic inflammations in the male genital tract have long been linked with infertility, possibly via affecting the sperm epigenome or its surrounding microenvironment. This review article summarizes the relationship between epigenome, inflammation, and its contribution to male infertility.</p> Divya Adiga Sangavi Eswaran Sriharikrishnaa S Nadeem Khan G Shama Prasada Kabekkodu Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 140 155 Antioxidants, anti-inflammatory drugs and antibiotics in the treatment of reproductive tract infections and their association with male infertility <p>Male infertility is a multifactorial condition which in some cases are presented with unidentifiable underlying causes. Men with idiopathic or non-curable oligoasthenoteratozoospermia as well as with unexplained infertility may be provided with non-hormonal medical treatment which includes the use of anti-inflammatory, antioxidants, fibrinolytic compounds, vitamin supplementation, and oligo-elements, presuming that most of these cases are possibly caused by inflammation and/or oxidative stress. In the case of the known pathogenic mechanisms responsible for male infertility, the treatments include specific antibiotics targeting the exact pathogenic strains, anti-inflammatory drugs targeting particular infections, as well as the use of antioxidants, singly or in combinations to ameliorate the detected oxidative stress. Combined non-hormonal therapies have also shown to improve semen quality. Since there is a lack of consensus regarding the exact dose, duration and effects of non-hormonal treatment on male infertility, this review article aims to present a comprehensive summary of how antioxidants, anti-inflammatory drugs and antibiotics treatment in reproductive tract infections are associated with amelioration of male fertility parameters.</p> Emmanuel Izuka Ifeanyi Menuba Pallav Sengupta Sulagna Dutta Uchenna Nwagha Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 156 165 Reproductive Inflammatory Mediators and Male Infertility <p>Disruption of semen quality in cases of testicular and accessory gland infections, owe to altered spermatogenesis, sperm maturation and/or transport. The impact depends on the intensity, duration of progression, mediators of the inflammatory process and individual susceptibility to the infection. Interactions among the mediators with immunological cells and other regulators affect sperm function and have been reported to be associated with male infertility. However, the issue is still under debate and paves several dimensions of research in this realm. The summarized discussion of articles about the current knowledge on male reproductive tract inflammation and causative agents with its consequences on male reproductive functions have been included.</p> Sulagna Dutta Pallav Sengupta Bhupender S. Chhikara Copyright (c) 2020 ScienceIn Publishing 2020-03-16 2020-03-16 7 2 73 74