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This chapter explores the possibility that capacitation and apoptosis are linked processes joined by their common dependence on the continued generation of reactive oxygen species (ROS). According to this model capacitation is initiated in spematozoa following their release into the female reproductive tract as a consequence of intracellular ROS generation, which stimulates intracellular cAMP generation, inhibits tyrosine phosphatase activity and enhances the formation of oxysterols prior to their removal from the sperm surface by albumin. The continued generation of ROS by capacitating populations of spermatozoa eventually overwhelms the limited capacity of these cells to protect themselves from oxidative stress. As a result the over-capacitation of spermatozoa leads to a state of senescence and the activation of a truncated intrinsic apoptotic cascade characterized by enhanced mitochondrial ROS generation, lipid peroxidation, motility loss, caspase activation and phosphatidylserine externalization. The latter may be particularly important in instructing phagocytic leukocytes that the removal of senescent, moribund spermatozoa should be a silent process unaccompanied by the generation of proinflammatory cytokines. These observations reveal the central role played by redox chemistry in defining the life and death of spermatozoa. A knowledge of these mechanisms may help us to engineer novel solutions to both support and preserve the functionality of these highly specialized cells. [ABSTRACT FROM AUTHOR]

One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high levels of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair (BER) pathway, 8-oxoguanine glycosylase 1 (OGG1). The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins (APE1, XRCC1) needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceived in vitro and serves as a driver for current research into the origins of free radical generation in the germ line. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels. This is a cross-sectional study conducted at Androscience, Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo, Brazil, with 508 male patients, aged 18-60 years, from 2007 to 2017. Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria. Patients were divided into normozoospermic group (NZG, n = 124) and a group with seminal abnormalities (SAG, n = 136). Evaluation included complete physical examination, past medical history, habits and lifestyle factors, two complete seminal analysis with sperm functional tests, serum levels of 25-hydroxy-vitamin D 3 (25(OH)VD 3 ), total and free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR) index, and karyotype. The mean concentration of 25(OH)VD 3 was significantly lower in the SAG (P < 0.001) and positively correlated with all baseline seminal parameters and total testosterone levels. In addition, serum vitamin D 3 concentration was found to be positively correlated with sperm concentration (β= 2.103; P < 0.001), total number of spermatozoa with progressive motility (β = 2.069; P = 0.003), total number of motile spermatozoa (β = 2.571; P = 0.015), and strict morphology (β = 0.056; P = 0.006), regardless of other variables. This is the first comparative study to address the issue of serum vitamin D 3 content between normozoospermic patients and those with sperm abnormalities. It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality, male reproductive potential, and testosterone levels., Competing Interests: None