Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia) can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia.

Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia–reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs.

Reactive oxygen species such as superoxide anion radicals (O2 (-) ) and hydrogen peroxide (H2 O2 ) have for long time been recognized as undesirable by-products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiological conditions such as those activated in hypoxic microenvironments. The molecular response to hypoxia requires fast-acting mechanisms acting within a wide range of partial pressures of oxygen (O2 ). Intracellular O2 sensing is an evolutionary preserved feature, and the best characterized molecular responses to hypoxia are mediated through transcriptional activation. The transcription factor, hypoxia-inducible factor 1 (HIF-1), is a critical mediator of these adaptive responses, and its activation by hypoxia involves O2 -dependent posttranslational modifications and nuclear translocation. Through the induction of the expression of its target genes, HIF-1 coordinately regulates tissue O2 supply and energetic metabolism. Other transcription factors such as nuclear factor κB are also redox sensitive and are activated in pro-oxidant and hypoxic conditions. The purpose of this review is to summarize new developments in HIF-mediated O2 sensing mechanisms and their interactions with reactive oxygen species-generating pathways in normal and abnormal physiology.

Hypobaric hypoxia (HH), an environmental condition of high altitude encountered by mountaineers, miners, and observatory, rural health, border patrol, and rural education workers, jeopardizes normal physiologic functions in humans. The present study was conducted to evaluate the effects of intermittent HH (IHH; equivalent to 4600 m above mean sea level) on oxidative stress and the protective role of dietary ascorbic acid on rat testis and epididymis. Ten-week-old male Wistar rats were assigned to 1 of 6 groups: 1) normobaric (Nx), 2) Nx + physiologic solution (Nx + PS), 3) Nx + ascorbic acid (Nx + AA), 4) IHH, 5) IHH + PS, or 6) IHH + AA. Animals subjected to IHH were exposed for 96 hours followed by normobaric conditions for 96 hours for a total of 32 days. The control groups (2 and 5) were injected with doses of PS, and the treated groups (3 and 6) were injected with doses of AA (10 mg 6kg 21 body weight) at an interval of 96 hours. Rats were sacrificed on day 32 after initiation of the protocol. The testis and epididymis were collected to determine the activity and expression of glutathione reductase and the levels of lipid peroxide formation. An epididymal sperm count was also performed in each animal. The results of this study revealed that IHH induced lipid peroxidation, a reduction in glutathione reductase activity in testis and epididymis, and a significant decrease in epididymal sperm count. Treatment with AA prevented these changes. In conclusion, AA was capable of decreasing oxidative stress in testis and epididymis under IHH. This protection by AA of the IHH-induced lipid peroxidation can be explained in part by the preservation of glutathione reductase activity in these organs.

Since the 1970s, the establishment and development of the biotech industry has improved exponentially, allowing the commercial production of biopharmaceutical proteins. Nowadays, new recombinant protein production is considered a multibillion-dollar market, in which about 25% of commercial pharmaceuticals are biopharmaceuticals. But to achieve a competitive production process is not an easy task. Any production process has to be highly productive, efficient and economic. Despite that the perfect host is still not discovered, several research groups have chosen Pichia pastoris as expression system for the production of their protein because of its many features. The attempt of this review is to embrace several research lines that have adopted Pichia pastoris as their expression system to produce a protein on an industrial scale in the health care industry.