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MANAGEMENT OF SPERM DNA DAMAGE In addition to the development of novel procedures for sperm isolation and recovery, we might also explore measures to better manage sperm DNA damage, in cases where the etiology is known. For example, if oxidative stress is centrally involved in the etiology of sperm DNA damage, we might ask what factors are involved in creating such stress to the point that both the genetic and epigenetic integrity of the spermatozoa are significantly compromised. Keywords: clinical; DNA damage; etiology; management; oxidative stress; spermatozoa EN clinical DNA damage etiology management oxidative stress spermatozoa 1541 1544 4 10/24/23 20231101 NES 231101 Since the pioneering studies by Don Evenson and colleagues first opened our eyes to the existence of DNA damage in subpopulations of human spermatozoa,[1] important questions have been raised concerning the causes, clinical significance, and resolution of this phenomenon.[2] In this Special Issue of Andrology, we have brought together a collection of cutting-edge research articles and reviews, reflecting the most recent advances in this area. [Extracted from the article]

This review surveys the causes and consequences of DNA damage in the male germ line from spermatogonial stem cells to fully differentiated spermatozoa. Within the stem cell population, DNA integrity is well maintained as a result of excellent DNA surveillance and repair; however, a progressive increase in background mutation rates does occur with paternal age possibly as a result of aberrant DNA repair as well as replication error. Once a germ cell has committed to spermatogenesis, it responds to genetic damage via a range of DNA repair pathways or, if this process fails, by the induction of apoptosis. When fully‐differentiated spermatozoa are stressed, they also activate a truncated intrinsic apoptotic pathway which results in the activation of nucleases in the mitochondria and cytoplasm; however, the physical architecture of these cells prevents these enzymes from translocating to the nucleus to induce DNA fragmentation. Conversely, hydrogen peroxide released from the sperm midpiece during apoptosis is able to penetrate the nucleus and induce DNA damage. The base excision repair pathway responds to such damage by cleaving oxidized bases from the DNA, leaving abasic sites that are alkali‐labile and readily detected with the comet assay. As levels of oxidative stress increase and these cells enter the perimortem, topoisomerase integrated into the sperm chromatin becomes activated by SUMOylation. Such activation may initially facilitate DNA repair by reannealing double strand breaks but ultimately prepares the DNA for destruction by nucleases released from the male reproductive tract. The abasic sites and oxidized base lesions found in live spermatozoa are mutagenic and may increase the mutational load carried by the offspring, particularly in the context of assisted conception. A variety of strategies are described for managing patients expressing high levels of DNA damage in their spermatozoa, to reduce the risks such lesions might pose to offspring health. [ABSTRACT FROM AUTHOR]

Keywords: oxidative stress; reactive oxygen species; seminal plasma; sperm EN oxidative stress reactive oxygen species seminal plasma sperm 1579 1580 2 10/24/23 20231101 NES 231101 Spermatozoa are particularly vulnerable to oxidative attack because they are so well endowed with long chain polyunsaturated fatty acids, designed give the plasma membrane the fluidity it needs to participate in the membrane fusion events associated with fertilization. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. [Extracted from the article]

As COVID‐19 infections wreak havoc across the globe, attention has rightly been focused on the vital organ systems (lung, kidney and heart) that are vulnerable to viral attack and contribute to the acute pathology associated with this disease. However, we should not lose sight of the fact that COVID‐19 will attack any cell type in the body expressing ACE2 ‐ including human spermatozoa. These cells possess the entire repertoire of receptors (AT1R, AT2R, MAS) and ligand processing enzymes (ACE1 and ACE2) needed to support the angiotensin signalling cascade. The latter not only provides COVID‐19 with a foothold on the sperm surface but may also promote integration, given the additional presence of a range of proteases (TMPRSS2, TMPRSS11B, TMPRSS12, furin) capable of promoting viral fusion. This article reviews the roles played by these various cellular constituents in maintaining the vitality of human spermatozoa and their competence for fertilization. The reproductive consequences of a viral attack on these systems, in terms of fertility and the risk of sexual transmission, are currently unknown. However, we should be alive to the possibility that there may be reproductive consequences of COVID‐19 infection in young males that go beyond their capacity to survive a viral attack. [ABSTRACT FROM AUTHOR]

Background Material and methods Results and discussion Conclusions The escalating prevalence of fertility problems in the aging population necessitates a comprehensive exploration of contributing factors, extending beyond environmental concerns, work‐related stress, and unhealthy lifestyles. Among these, the rising incidence of testicular disorders emerges as a pivotal determinant of fertility issues. Current treatment challenges are underscored by the limitations of high‐dose and frequent drug administration, coupled with substantial side effects and irreversible trauma inflicted by surgical interventions on testicular tissue.The formidable barrier posed by the blood–testis barrier compounds the complexities of treating testicular diseases, presenting a significant therapeutic obstacle. The advent of nanocarriers, with their distinctive attributes, holds promise in overcoming this impediment. These nanocarriers exhibit exceptional biocompatibility, and membrane penetration capabilities, and can strategically target the blood–testis barrier through surface ligand modification, thereby augmenting drug bioavailability and enhancing therapeutic efficacy.This review concentrates on the transformative potential of nanocarriers in the delivery of therapeutic agents to testicular tissue. By summarizing key applications, we illuminate the strides made in utilizing nanocarriers as a novel avenue to effectively treat testicular diseases.Nanocarriers are critical in delivering therapeutic agents to testicular tissue. [ABSTRACT FROM AUTHOR]