The Effect of Statins on Male Reproductive Parameters: A Mechanism Involving Dysregulation of Gonadal Hormone Receptors and TRPV1.

Statins have been shown to cause diverse male reproductive function impairment, and in some cases, orchialgia. Therefore, the current study investigated the possible mechanisms through which statins may alter male reproductive parameters. Thirty adult male Wistar rats (200-250 g) were divided into three groups. The animals were orally administered rosuvastatin (50 mg/kg), simvastatin (50 mg/kg), or 0.5% carboxy methyl cellulose (control), for a 30-day period. Spermatozoa were retrieved from the caudal epididymis for sperm analysis. The testis was used for all biochemical assays and immunofluorescent localization of biomarkers of interest. Rosuvastatin-treated animals presented with a significant decrease in sperm concentration when compared to both the control and simvastatin groups (p < 0.005). While no significant difference was observed between the simvastatin and the control group. The Sertoli cells, Leydig cells and whole testicular tissue homogenate expressed transcripts of solute carrier organic anion transporters (SLCO1B1 and SLCO1B3). There was a significant decrease in the testicular protein expression of the luteinizing hormone receptor, follicle stimulating hormone receptor, and transient receptor potential vanilloid 1 in the rosuvastatin and simvastatin-treated animals compared to the control. The expression of SLCO1B1, SLCO1B2, and SLCO1B3 in the different spermatogenic cells portray that un-bio transformed statin can be transported into the testicular microenvironment, which can subsequently alter the regulation of the gonadal hormone receptors, dysregulate pain-inflammatory biomarkers, and consequently impair sperm concentration.

Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology.

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

Bisphenol A and Male Infertility: Role of Oxidative Stress.

Bisphenol A (BPA) is an endocrine-disrupting chemical that is capable of mimicking, antagonizing, and interfering with the normal biological functioning of the endocrine system. BPA is used in diverse industries, hence its vast sources of exposure. Although the half-life of BPA is relatively short (<24 hours), studies have reported its detection in the urine of different populations. It, therefore, became important to investigate its effect on general health, including male reproductive health. The adverse effects of BPA on male fertility have been evaluated and reported from both in vivo and in vitro studies. Up to date, reports from randomized controlled trials remain controversial, as some revealed decreased sperm quality, sperm concentration, and total sperm count, while others reported that no adverse effect was seen after exposure. Findings from animal model studies and in vitro experiments have shown that exposure to BPA led to a reduction in sperm quality and increased sperm DNA fragmentation, and some even revealed altered expression of the gene that encodes gonadotropin-releasing hormone. This shows that BPA not only may adversely affect male fertility by acting as an endocrine disruptor but also can potentially impact male fertility via its possible contribution to oxidative stress. Therefore, this book chapter aims to identify and elucidate the effect of BPA exposure on male fertility, and to as well illustrate the mechanisms through which this occurs, while emphasizing the role of oxidative stress as a potential pathway.

Computational Analysis of Short Linear Motifs in the Spike Protein of SARS-CoV-2 Variants Provides Possible Clues into the Immune Hijack and Evasion Mechanisms of Omicron Variant.

Short linear motifs (SLiMs) are short linear sequences that can mediate protein-protein interaction. Mimicking eukaryotic SLiMs to compete with extra- or intracellular binding partners, or to sequester host proteins is the crucial strategy of viruses to pervert the host system. Evolved proteins in viruses facilitate minimal protein-protein interactions that significantly affect intracellular signaling networks. Unfortunately, very little information about SARS-CoV-2 SLiMs is known, especially across SARS-CoV-2 variants. Through the ELM database-based sequence analysis of spike proteins from all the major SARS-CoV-2 variants, we identified four overriding SLiMs in the SARS-CoV-2 Omicron variant, namely, LIG_TRFH_1, LIG_REV1ctd_RIR_1, LIG_CaM_NSCaTE_8, and MOD_LATS_1. These SLiMs are highly likely to interfere with various immune functions, interact with host intracellular proteins, regulate cellular pathways, and lubricate viral infection and transmission. These cellular interactions possibly serve as potential therapeutic targets for these variants, and this approach can be further exploited to combat emerging SARS-CoV-2 variants.

Fertility and pregnancy outcome among women undergoing assisted reproductive technology treatment in Windhoek, Namibia.

PURPOSE: Infertility has been defined as a couple's failure to conceive after regular and unprotected coitus for 1 year or six months, depending on the age of the female counterpart. Although infertility can result from both the male and/or the female, often the female partner faces pressure since it is believed in some African cultures that a woman without children is like a tree without leaves. The aim of this study was to determine the prevalence of successful pregnancy outcomes among infertile women undergoing assisted reproductive technology (ART) treatment at the Cape Windhoek Fertility Clinic. METHODS: This was a prospective and descriptive cross-sectional case reference study encompassing 178 infertile women visiting the Cape Windhoek Fertility Clinic for ART treatment. RESULTS: The vast majority of the participants (81.5%) were married women. From the 178 infertile women, 96 (53.9%) suffered from primary and 82 (46.1%) from secondary infertility. The predominant cause of complications for infertility among the women studied was defective ovulation (28.7%) and the most common ART treatment administered was IVF/ICSI (52.2%). Only a third (33.1%) of the women who received ART treatment eventually fell pregnant. CONCLUSION: The outcome of this study may not give a clear indication of the prevalence of infertility among women in the entire Namibian nation due to the costs involved with ART treatment offered mainly at privately owned hospitals and/or clinics, thereby resulting in those who cannot afford treatment to be left out despite being infertile.

The Role of Selected Natural Biomolecules in Sperm Production and Functionality.

Emerging evidence from in vivo as well as in vitro studies indicates that natural biomolecules may play important roles in the prevention or management of a wide array of chronic diseases. Furthermore, the use of natural compounds in the treatment of male sub- or infertility has been proposed as a potential alternative to conventional therapeutic options. As such, we aimed to evaluate the effects of selected natural biomolecules on the sperm production, structural integrity, and functional activity. At the same time, we reviewed their possible beneficial or adverse effects on male reproductive health. Using relevant keywords, a literature search was performed to collect currently available information regarding molecular mechanisms by which selected natural biomolecules exhibit their biological effects in the context of male reproductive dysfunction. Evidence gathered from clinical trials, in vitro experiments and in vivo studies suggest that the selected natural compounds affect key targets related to sperm mitochondrial metabolism and motion behavior, oxidative stress, inflammation, DNA integrity and cell death. The majority of reports emphasize on ameliorative, stimulating and protective effects of natural biomolecules on the sperm function. Nevertheless, possible adverse and toxic behavior of natural compounds has been indicated as well, pointing out to a possible dose-dependent impact of natural biomolecules on the sperm survival and functionality. As such, further research leading to a deeper understanding of the beneficial or adverse roles of natural compounds is necessary before these can be employed for the management of male reproductive dysfunction.

SARS-CoV-2 and the testis: similarity with other viruses and routes of infection.

Since the start of the latest coronavirus (SARS-CoV-2) outbreak, the number of infected individuals and cases of coronavirus disease (COVID-19) has been increasing exponentially worldwide. Of interest is existing evidence that orchitis can develop due coronavirus infection. It is therefore not unreasonable to believe that SARS-CoV-2 could be transmitted by semen. Consequently, it is of paramount importance that individuals who could potentially be infected take all possible care to mitigate the likely risk of passing on the infection through sexual intercourse.

The Uruguayan semen donor population: A twenty-eight-year retrospective study.

Several studies have reported a global decline in seminal quality over the years. The objective of this study was to describe the semen donor population of Uruguay through comparing data of successive samples banked by the same donors and the analysis of their semen and physical characteristics, ancestry origin and educational level. A total of 3,449 ejaculated samples collected from 71 donors, cryobanked between 1989 and March 2017 at Fertilab, were analysed. Results revealed a mean age of 23.90 ± 3.98 years, an average weight of 74.95 ± 1.09 kg and a mean height of 1.78 ± 0.06 m. The majority of the donors trace their origin to Europe (74.65%, 53/71) and 66.19% (47/71) have a level of education higher than secondary school. We observed longitudinal differences in two parameters, that is sperm concentration and semen volume. Sperm concentration declined, while semen volume increased significantly over the 28-year period. The results of the present study are in accordance with that of previous articles that also reported a decline in sperm concentration over time. However, no differences were observed in total sperm number per ejaculate due to the increase in semen volume values, thus reflecting no real changes in sperm production over time.

Improved sperm motility after 4 h of ejaculatory abstinence: role of accessory sex gland secretions.

Various studies have sought to determine the typical v. optimal abstinence period after which semen samples should be collected, with many contradictory results reported. Several factors influence the semen microenvironment, and thus sperm parameters. In this study we focused on the secretions of the prostate, seminal vesicles and the epididymis. Semen samples were obtained from healthy normozoospermic males (n=16) after 4-day and 4-h periods of ejaculatory abstinence, and standard semen analysis was performed using computer-aided sperm analysis, whereas seminal plasma citric acid, neutral α-glucosidase and fructose concentrations were measured using assay kits. There were significant decreases in total sperm count (P<0.001), sperm concentration (P<0.05) and semen volume (P<0.05) after 4h compared with 4 days ejaculatory abstinence. Furthermore, increases were observed in total sperm motility (P<0.05) and sperm progressive motility (P<0.01) after a 4-h abstinence period, accompanied by significant reductions in citric acid (P<0.05), α-glucosidase (P<0.01) and fructose (P<0.01) concentrations. In addition, due to the decreased number of spermatozoa, these concentrations translated to a significant decrease in fructose (P<0.05) per spermatozoon, indicating an intrinsic mechanism capitalising on alternative sources of energy for increased metabolic function and subsequent sperm motility.

Current perspectives of CASA applications in diverse mammalian spermatozoa.

Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.

Influence of ejaculation frequency on seminal parameters.

BACKGROUND: Several factors have been shown to influence semen parameters, one of which is sexual abstinence; a clinical criteria included in the semen evaluation to provide maximum sperm quality. The aim of the present study was to assess the effect of a daily ejaculation frequency on conventional and functional semen parameters. METHODS: Semen samples were collected daily over a period of two weeks of which every second sample per person was processed and analyzed according to the World Health Organization guidelines. Furthermore, mitochondrial function, intracellular reactive oxygen species production and sperm DNA fragmentation were evaluated by flow cytometry. RESULTS: Total sperm count and seminal volume per ejaculation declined and remained decreased for the duration of the daily ejaculation period. However, conventional parameters such as sperm concentration, motility, progressive motility, morphology, vitality and functional parameters such as sperm plasma membrane integrity, mitochondrial membrane potential and DNA fragmentation was not significantly affected and remained similar to the initial measurement throughout the daily ejaculation period. Despite intra- and inter individual variations, the average values of the basic semen parameters remained above the WHO (2010) reference values throughout the daily ejaculation period. Interestingly, a decreasing trend in intracellular ROS production was observed, although statistically not significant. CONCLUSIONS: The study shows that an extended 2 week period of daily ejaculation does not have major clinical effects on conventional and functional seminal parameters.

Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility.

Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus-pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system.

Contemporary evidence on the physiological role of reactive oxygen species in human sperm function.

Reactive oxygen species (ROS) play an important role in male fertility. Overproduction of reactive oxygen species (ROS) has been associated with a variety of male fertility complications, including leukocytospermia, varicocele and idiopathic infertility. The subsequent oxidative insult to spermatozoa can manifest as insufficient energy metabolism, lipid peroxidation and DNA damage, leading to loss of motility and viability. However, various studies have demonstrated that physiological amounts of ROS play important roles in the processes of spermatozoa maturation, capacitation, hyperactivation and acrosome reaction. It is therefore crucial to define and understand the delicate oxidative balance in male reproductive cells and tissues for a better understanding of both positive as well as negative impact of ROS production on the fertilizing ability. This review will discuss the specific physiological roles, mechanisms of action and effects that ROS have on the acquisition of structural integrity and physiological activity of spermatozoa.

Utility of antioxidants during assisted reproductive techniques: an evidence based review.

Assisted reproductive technology (ART) is a common treatment of choice for many couples facing infertility issues, be it due to male or female factor, or idiopathic. Employment of ART techniques, however, come with its own challenges as the in vitro environment is not nearly as ideal as the in vivo environment, where reactive oxygen species (ROS) build-up leading to oxidative stress is kept in check by the endogenous antioxidants system. While physiological amounts of ROS are necessary for normal reproductive function in vivo, in vitro manipulation of gametes and embryos exposes these cells to excessive ROS production either by endogenous or exogenous environmental factors. In this review, we discuss the sources of ROS in an in vitro clinical setting and the influence of oxidative stress on gamete/embryo quality and the outcome of IVF/ICSI. Sources of ROS and different strategies of overcoming the excessive generation of ROS in vitro are also highlighted. Endogenously, the gametes and the developing embryo become sources of ROS. Multiple exogenous factors act as potential sources of ROS, including exposure to visible light, composition of culture media, pH and temperature, oxygen concentration, centrifugation during spermatozoa preparation, ART technique involving handling of gamete/embryo and cryopreservation technique (freeze/thawing process). Finally, the use of antioxidants as agents to minimize ROS generation in the in vitro environment and as oral therapy is highlighted. Both enzymatic and non-enzymatic antioxidants are discussed and the outcome of studies using these antioxidants as oral therapy in the male or female or its use in vitro in media is presented. While results of studies using certain antioxidant agents are promising, the current body of evidence as a whole suggests the need for further well-designed and larger scale randomized controlled studies, as well as research to minimize oxidative stress conditions in the clinical ART setting.

Implications of Exposure to Air Pollution on Male Reproduction: The Role of Oxidative Stress.

Air pollution, either from indoor (household) or outdoor (ambient) sources, occurs when there is presence of respirable particles in the form of chemical, physical, or biological agents that modify the natural features of the atmosphere or environment. Today, almost 2.4 billion people are exposed to hazardous levels of indoor pollution, while 99% of the global population breathes air pollutants that exceed the World Health Organization guideline limits. It is not surprising that air pollution is the world's leading environmental cause of diseases and contributes greatly to the global burden of diseases. Upon entry, air pollutants can cause an increase in reactive oxygen species (ROS) production by undergoing oxidation to generate quinones, which further act as oxidizing agents to yield more ROS. Excessive production of ROS can cause oxidative stress, induce lipid peroxidation, enhance the binding of polycyclic aromatic hydrocarbons (PAHs) to their receptors, or bind to PAH to cause DNA strand breaks. The continuous and prolonged exposure to air pollutants is associated with the development or exacerbation of pathologies such as acute or chronic respiratory and cardiovascular diseases, neurodegenerative and skin diseases, and even reduced fertility potential. Males and females contribute to infertility equally, and exposure to air pollutants can negatively affect reproduction. In this review, emphasis will be placed on the implications of exposure to air pollutants on male fertility potential, bringing to light its effects on semen parameters (basic and advanced) and male sexual health. This study will also touch on the clinical implications of air pollution on male reproduction while highlighting the role of oxidative stress.

Proteomic analysis of seminal fluid from men exhibiting oxidative stress.

BACKGROUND: Seminal plasma serves as a natural reservoir of antioxidants. It helps to remove excessive formation of reactive oxygen species (ROS) and consequently, reduce oxidative stress. Proteomic profiling of seminal plasma proteins is important to understand the molecular mechanisms underlying oxidative stress and sperm dysfunction in infertile men. METHODS: This prospective study consisted of 52 subjects: 32 infertile men and 20 healthy donors. Once semen and oxidative stress parameters were assessed (ROS, antioxidant concentration and DNA damage), the subjects were categorized into ROS positive (ROS+) or ROS negative (ROS-). Seminal plasma from each group was pooled and subjected to proteomics analysis. In-solution digestion and protein identification with liquid chromatography tandem mass spectrometry (LC-MS/MS), followed by bioinformatics analyses was used to identify and characterize potential biomarker proteins. RESULTS: A total of 14 proteins were identified in this analysis with 7 of these common and unique proteins were identified in both the ROS+ and ROS- groups through MASCOT and SEQUEST analyses, respectively. Prolactin-induced protein was found to be more abundantly present in men with increased levels of ROS. Gene ontology annotations showed extracellular distribution of proteins with a major role in antioxidative activity and regulatory processes. CONCLUSIONS: We have identified proteins that help protect against oxidative stress and are uniquely present in the seminal plasma of the ROS- men. Men exhibiting high levels of ROS in their seminal ejaculate are likely to exhibit proteins that are either downregulated or oxidatively modified, and these could potentially contribute to male infertility.

The effect of Aspalathin linearis, Cyclopia intermedia and Sutherlandia frutescene on sperm functional parameters of healthy male wistar rats.

Introduction: Rooibos (Aspalathin linearis), honeybush (Cyclopia intermedia), and sutherlandia (Sutherlandia frutescene) are three Southern Africa indigenous plants, of which the extracts have become house-hold items and are consumed on a large scale. Although, they are known for their antioxidant properties, studies have highlighted danger in the excessive intake. Therefore, the current study investigated whether treatment with rooibos, honeybush, and sutherlandia will impact sperm functional parameters positively or otherwise, in healthy rats. Methods: Fourteen-week-old pathogen-free adult male Wistar rats (250-300 g) were randomly divided into four groups of ten, including a control, rooibos (RF), honeybush (HB) and a sutherlandia (SL) group. After 7 weeks of treatment, animals were sacrificed. Spermatozoa were retrieved from the cauda epididymis for motility, morphology and concentration analysis and the testis was used for all biochemical assays. Results: The infusion treated animals (RF, HB, and SL) presented with a non-significant decrease of -14.3%, -18.2%, -17.2% and -24.8%, -20.7%, -27.3% in total motility and progressive motility when compared to the control group, respectively. There was a significant increase in number of spermatozoa with slow speed (p = 0.03), especially in SL treated group compared to the control (p = 0.03). Additionally, there was an increase of 28.8%, 31.7%, 23% in superoxide dismutase (SOD) activity of RF, HB and SL compared to control, respectively. This was accompanied with a percentage decrease of -21.1%, -23.7%, 45.9% in malondialdehyde (MDA) levels compared to the control group. Conclusion: In summary, animals treated with the respective infusions presented with a percentage increase in SOD activity but have reduced sperm motility and decreased normal morphology. Paradoxically, they presented with increased sperm concentration. Hence, it is presumed that rooibos, honeybush and sutherlandia may enhance sperm quantity (concentration) but may impair sperm quality (motility morphology) when consumed by healthy animals.

Could exposure to spaceflight cause mutations in genes that affect male fertility?

Recently, a study reported that upon analyzing blood samples from 14 astronauts that flew Space Transportation System missions between 1998 and 2001, 34 somatic nonsynonymous single nucleotide variants were detected in 17 CH-driver genes. Of interest is that the cohort consisted of relatively young astronauts, 85% of which were males of reproductive age. Having investigated the genes with nonsynonymous substitutes from the literature, it was found that twelve of these 17 genes appear to play essential roles in male reproduction. Changes in telomere length and gene regulation were also reported in another study conducted on an astronaut during a long duration stay on the International Space Station. Realizing the impact of spaceflight on gene sequence with potential influence on male fertility, it is important that more studies are conducted in this field. Specifically, in light of ultimately colonizing space, multi-generational survival is crucial and strategies to mitigate or counteract such effects should be explored.