Anandan Das

Reactive oxygen species (ROS) are oxygen-containing molecules which are reactive in nature and are capable of independent existence in the body. ROS comprise mostly of free radicals that contain at least one unpaired electron. Endogenous sources are the foremost birthplaces of ROS, which include mitochondrial electron transport chain, endoplasmic reticulum and peroxisome. Conversely, numerous enzymatic pathways such as xanthine oxidase and cyclooxygenase systems are among the prominent generators of cellular ROS. Major sources of ROS in the female reproductive tract include Graafian follicles, follicular fluid, fallopian tube, peritoneal cavity and endometrium. On the contrary, leukocytes, immature spermatozoa and varicocele are the key originators of ROS in the male reproductive system. For the sake of maintaining a proper oxidative balance, cells have evolved a variety of antioxidative molecules. From the physiological perspective, ROS and antioxidants are actively involved in the regulation of myriad female reproductive processes, such as cyclic luteal and endometrial changes, follicular development, ovulation, fertilization, embryonic implantation, maintenance of pregnancy and parturition. Similarly, physiological amounts of ROS are crucial in the accomplishment of various male reproductive functions as well, which include spermatozoa maturation, capacitation, hyperactivation and acrosome reaction. This chapter highlights the birthplaces of ROS in the female and male reproductive tract along with mechanisms of their production. This chapter will also put forward specific physiological roles of these reactive molecules in upholding the structural integrity and functionality of both the reproductive systems. Keywords Oxidative stress Free radicals Female Endometrium Ovulation Implantation Male Spermatozoa Hyperactivation Acrosome reaction

Radiotherapy, a popular cancer management procedure, negatively impacts reproductive health particularly by reducing the fertility potential. The purpose of this study was to analyze the research trend in radiotherapy associated with male infertility over the past 20 years (2000-May 2021). SCOPUS database was used to retrieve relevant scientometric data (publication per year, affiliation, journals, countries, type of document and area of research) for different subgenres of radiotherapy and male infertility. A total of 275 articles were published related to radiotherapy and male infertility, with the United States being the most dominant country in research output in this field. Radiotherapy and male infertility research have shown positive growth over the last two decades. In-depth analysis revealed that publications (n) related to radiotherapy and male infertility research mainly focused its impact on semen parameters (n = 155) and fertility preservation techniques (n = 169). Our scientometric results highlight a limited research focus on the field of radiotherapy and its impact on male reproductive hormones. Furthermore, a significant lack of research was noticed in the area of omics and male reproductive organs linked to radiotherapy. Substantial research is warranted to further decipher the effect of radiotherapy, at molecular level, leading to male infertility.

Hypogonadism is an endocrine disorder characterized by inadequate serum testosterone production by the Leydig cells of the testis. It is triggered by alterations in the hypothalamic–pituitary–gonadal axis. Erectile dysfunction (ED) is another common disorder in men that involves an alteration in erectile response–organic, relational, or psychological. The incidence of hypogonadism and ED is common in men aged over 40 years. Hypogonadism (including late-onset hypogonadism) and ED may be linked to several environmental factors-induced oxidative stresses. The factors mainly include exposure to pesticides, radiation, air pollution, heavy metals and other endocrine-disrupting chemicals. These environmental risk factors may induce oxidative stress and lead to hormonal dysfunctions. To better understand the subject, the study used many keywords, including “hypogonadism”, “late-onset hypogonadism”, “testosterone”, “erectile dysfunction”, “reactive oxygen species”, “oxidative stress”, and “environmental pollution” in major online databases, such as SCOPUS and PUBMED to extract relevant scientific information. Based on these parameters, this review summarizes a comprehensive insight into the important environmental issues that may have a direct or indirect association with hypogonadism and ED in men. The study concludes that environmental factors-induced oxidative stress may cause infertility in men. The hypothesis and outcomes were reviewed critically, and the mechanistic approaches are applied through oxidant-sensitive pathways. This study also provides reccomendations on future therapeutic interventions and protective measures against such adverse environmental factors-induced hypogonadism and ED.

Pandemics are regarded as large-scale outbreaks of infectious disease that has the potential to significantly increase morbidity and mortality over a wide geographical area, which is accompanied by economic, social and political disruption. The likelihood of pandemic, especially caused by viral infectious diseases has increased over the past few years. The 21st century is just two decades old but it has already witnessed some of the deadliest viral pandemics having far-reaching consequences. These include Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) (2002), Influenza A virus subtype H1N1 (H1N1) (2009), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (2012) and Ebola virus (2013) and the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) (2019-present). The viruses may adopt various mechanisms to invade and hijack the cellular machinery of the host cell, followed by infection-mediated immunomodulation and progressive inflammation, which in turn, may affect the functioning of different organ systems of the body. Although effective commercial vaccines are unavailable for most of these viruses, those against SARS-CoV-2 are being developed at an unprecedented speed with few of the vaccines already being approved for commercial distribution. Significant policy attention is required to limit the outbreak of such pandemics and to expand and sustain investment to build preparedness and health capacity.

Coronavirus disease 2019 (COVID-19) has emerged as a new public health crisis, threatening almost all aspects of human life. Originating in bats, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted to humans through unknown intermediate hosts, where it is primarily known to cause pneumonia-like complications in the respiratory system. Organ-to-organ transmission has not been ruled out, thereby raising the possibility of the impact of SARS-CoV-2 infection on multiple organ systems. The male reproductive system has been hypothesized to be a potential target of SARS-CoV-2 infection, which is supported by some preliminary evidence. This may pose a global threat to male fertility potential, as men are more prone to SARS-CoV-2 infection than women, especially those of reproductive age. Preliminary reports have also indicated the possibility of sexual transmission of SARS-CoV-2. It may cause severe complications in infected couples. This review focuses on the pathophysiology of potential SARS-CoV-2 infection in the reproductive organs of males along with their invasion mechanisms. The risks of COVID-19 on male fertility as well as the differences in vulnerability to SARS-CoV-2 infection compared with females have also been highlighted.

The twenty-first century has witnessed some of the deadliest viral pandemics with far-reaching consequences. These include the Human Immunodeficiency Virus (HIV) (1981), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) (2002), Influenza A virus subtype H1N1 (A/H1N1) (2009), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (2012) and Ebola virus (2013) and the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) (2019-present). Age- and gender-based characterizations suggest that SARS-CoV-2 resembles SARS-CoV and MERS-CoV with regard tohigher fatality rates in males, and in the older population with comorbidities. The invasion-mechanism of SARS-CoV-2 and SARS-CoV, involves binding of its spike protein with angiotensin-converting enzyme 2 (ACE2) receptors; MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), whereas H1N1 influenza is equipped with hemagglutinin protein. The viral infections-mediated immunomodulation, and progressive inflammatory state may affect the functions of several other organs. Although no effective commercial vaccine is available for any of the viruses, those against SARS-CoV-2 are being developed at an unprecedented speed. Until now, only Pfizer/BioNTech’s vaccine has received temporary authorization from the UK Medicines and Healthcare products Regulatory Agency. Given the frequent emergence of viral pandemics in the 21st century, proper understanding of their characteristics and modes of action are essential to address the immediate and long-term health consequences.