Porcine reproductive and respiratory syndrome virus infects the reproductive system of male piglets and impairs development of the blood-testis barrier.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood - testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and ß-catenin were downregulated in cell - cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H2O2, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.

Effects of Chicory (Cichorium intybus L.) Extract on Male Rat Reproductive System, Pregnancy and Offspring Development.

BACKGROUND: We recently reported that extract prepared from the aerial part of Cichorium intybus L. (CE) possesses hepatoprotective, hypolipidemic, and hypoglycemic properties. This paper focuses on the effects of CE on the male rat reproductive system and the effects of this treatment on pregnancy and offspring development. METHODS: The experimental male rats received 100 mg/kg bw/day, 500 mg/kg bw/day, and 1000 mg/kg bw/day of CE orally for 60 consecutive days. Rats that received tap water were used as controls. After treatment, we evaluated the effects of CE on the male reproductive system, fertility, and offspring development. RESULTS: For CE-treated male rats, there was a significant increase in the (1) diameter of seminiferous tubules, (2) spermatogenic index, (3) number of total and motile spermatozoa, and (4) testosterone levels. Additionally, there was a decrease in the pre- and post-implantation death of the embryos in the CE-treated group. All pups born from CE-treated males demonstrated normal development. CONCLUSIONS: CE treatment significantly improved male reproductive functions. No adverse effects on pregnancy and offspring development were observed when males were treated with CE. Further clinical evaluation of CE should lead to the development of a safe and effective phytodrug for treating male infertility.

Genotoxicity and cytotoxicity in male reproductive cells caused by sediment pollutants.

In recent years, mounting evidence has highlighted a global decline in male semen quality, paralleling an increase in male infertility problems. Such developments in the male reproductive system are likely due to a range of environmental factors, which could negatively affect the outcomes of pregnancy, reproductive health, and the well-being of fetuses. Different environmental contaminants ultimately accumulate in riverbed sediments due to gravity, so these sediments are frequently considered hotspots for pollutants. Therefore, understanding the detrimental effects of river sediment pollution on human reproductive health is crucial. This study indicates male germ cells' high vulnerability to environmental contaminants. There is a strong positive correlation between the concentration of complex accumulated pollutants from human activities and the reproductive toxicity observed in human testicular embryonic cell lines NCCIT and NTERA-2. This toxicity is characterized by increased levels of reactive oxygen species, disruption of critical cellular functions, genotoxic impacts, and the induction of cell apoptosis. This research marks a significant step in providing in vitro evidence of the damaging effects of environmental pollutants on the human male germline.

Phytochemical Screening, Antioxidant Effect and Sperm Quality of the Bomba ceiba Stamen Extracts on Charolais Cattle Sperm Induced by Ferrous Sulfate.

Orange Bombax ceiba (B. ceiba) is an indigenous plant, and its stamen is an important ingredient in traditional Lanna food. There are limitations in scientific reports on the effects of the biological activities of B. ceiba stamens on the male reproductive system. This study aims to investigate the phytochemical compounds of the orange B. ceiba stamen and its potential effect on the antioxidant properties and quality of cattle sperm treated with Fe. The orange BUE had the highest total phenolics, total tannins, total monomeric anthocyanins, and maximal antioxidant potential. The orange BAE had the highest concentration of total flavonoids. LC-QTOF/MS showed that the orange BUE contained the highest number of phytochemical compounds related to male reproductive enhancement. The orange BUE enhanced sperm motility, and both the orange BUE and the BAE enhanced sperm viability and normal sperm morphology via free radical scavenging. It might be suggested that B. ceiba stamens have benefits for sperm preservation, sperm quality, and increasing the economic value of local plants, and that they may be developed and used to guard against oxidative stress from cryodamage induced by frozen semen technology.

Radiation and male reproductive system: Damage and protection.

Male fertility has been declining in recent decades, and a growing body of research points to environmental and lifestyle factors as the cause. The widespread use of radiation technology may result in more people affected by male infertility, as it is well established that radiation can cause reproductive impairment in men. This article provides a review of radiation-induced damage to male reproduction, and the effects of damage mechanisms and pharmacotherapy. It is hoped that this review will contribute to the understanding of the effects of radiation on male reproduction, and provide information for research into drugs that can protect the reproductive health of males.

Trace and essential elements as vital components to improve the performance of the male reproductive system: Implications in cell signaling pathways.

Successful male fertilization requires the main processes such as normal spermatogenesis, sperm capacitation, hyperactivation, and acrosome reaction. The progress of these processes depends on some endogenous and exogenous factors. So, the optimal level of ions and essential and rare elements such as selenium, zinc, copper, iron, manganese, calcium, and so on in various types of cells of the reproductive system could affect conception and male fertility rates. The function of trace elements in the male reproductive system could be exerted through some cellular and molecular processes, such as the management of active oxygen species, involvement in the action of membrane channels, regulation of enzyme activity, regulation of gene expression and hormone levels, and modulation of signaling cascades. In this review, we aim to summarize the available evidence on the role of trace elements in improving male reproductive performance. Also, special attention is paid to the cellular aspects and the involved molecular signaling cascades.

Assessing the impact and mechanisms of environmental pollutants (heavy metals and pesticides) on the male reproductive system: a comprehensive review.

The escalation of technological advancements, coupled with the increased use of hazardous chemicals, has emerged as a significant concern for human health. Exposure to environmental pollutants like heavy metals and pesticides (insecticides, herbicides and fungicides) is known to significantly contribute to various health problems, particularly affecting reproductive health. Disturbances in reproductive potential and reproductive toxicity in males are particularly worrisome. Existing literature suggests that exposure to these environmental pollutants significantly alters male reproductive parameters. Thus, it is imperative to thoroughly analyze, comprehend, and evaluate their impact on male reproductive toxicity. Oxidative stress and disruptions in redox equilibrium are major factors through which these pollutants induce changes in sperm parameters and affect the reproductive system. Insecticides, fungicides, and herbicides act as endocrine disruptors, interfering with the secretion and function of reproductive hormones such as testosterone and luteinizing hormone (LH), consequently impacting spermatogenesis. Additionally, heavy metals are reported to bio-accumulate in reproductive organs, acting as endocrine disruptors and triggering oxidative stress. The co-operative association of these pollutants can lead to severe damage. In this comprehensive review, we have conducted an in-depth analysis of the impact of these environmental pollutants on the male reproductive system, shedding light on the underlying mechanisms of action.

Histochemical analysis, smooth muscle immunolocalization and volumetric density of the elastic system fibres of the ostrich (Struthio camelus) phallus.

There are few scientific reports on the histology of the phallus of ratite birds. The aim of this study was to conduct a histochemical analysis to determine the distribution of smooth muscle cells and the volumetric density (Vv) of the fibres of the elastic system in the ostrich phallus. Adult ostriches, 14 months old, were used. The phalluses were fixed in Bouin's solution and then transferred to a buffered formalin solution. They were then processed using standard histological stains for paraffin and slices were obtained. The following techniques were performed: HE, Picrosirius red, Alcian Blue at pH 1.0 and 2.5. The Periodic acid-Schiff reagent and Weigert's Resorcin-Fuchsin with previous oxidation were performed. The M42 test system was used to quantify the elastic system fibres. For immunohistochemical analysis, an anti alpha smooth muscle actin monoclonal antibody was used. The surface of the phallus is covered by a non-keratinized stratified squamous epithelium, which becomes stratified cylindrical in the region of the spermatic sulcus. No glands associated with the connective tissue were observed. The Vv of the elastic system fibres was 4.75%. Smooth muscle cells were visualized only in the walls of blood vessels through immunostaining, with an absence in the lymphatic sinuses. Despite similarities with other birds, such as the presence of a fibrous external axis, a lymphatic core, and a spermatic groove, the ostrich phallus shows marked differences, including the absence of an elastic core, a non-keratinized lining epithelium, and the absence of glands throughout its extension.

Histología testicular y morfología de la vejiga natatoria del pez neotropical Plagioscion magdalenae (Acanthuriformes: Sciaenidae): implicaciones en su taxonomía y distribución / Testicular histology and morphology of the swim bladder of the neotropical fish Plagioscion magdalenae (Acanthuriformes: Sciaenidae): implications in taxonomy and distribution

Introducción: La Pácora (Plagioscion magdalenae) es una especie nativa de Colombia y en categoría de casi amenazada a nivel del país, de la que poco se conoce acerca de las estructuras con aporte etológico en su historia de vida. Objetivo: Analizar el desarrollo gonadal relacionado con la espermatogénesis de P. magdalenae y las implicaciones taxonómicas a partir de la vejiga natatoria. Métodos: Realizamos siete muestreos en dos periodos climáticos: el primero en octubre de 2019 a febrero de 2020 de recolectas bimensuales y la segunda de octubre 2020 a enero 2021 de recolectas mensuales; con el fin de abarcar cada momento del pulso de inundación de la cuenca baja del Magdalena. Describimos la histomorfología testicular y las características macroscópicas de la vejiga natatoria de la especie. Además, analizamos aspectos como relaciones morfométricas, clases de tallas por sexos, la proporción sexual y la época de madurez sexual. Resultados: Analizamos 142 ejemplares y 4 intervalos de tallas fueron establecidos (entre 145 y 575 mm LE), 66 fueron machos y 73 hembras con una proporción sexual global 1.1:0.9 (hembra-macho) sin diferencias. Los machos tienen testículos de tipo tubular, protegidos por el peritoneo que se encuentra recubierto por la musculatura sónica de la vejiga natatoria, la cual posee forma de ''zanahoria'' sin apéndices, con dos bandas laterales de músculos intrínsecos (promedio entre 6.75 cm de largo y 1.48 cm de ancho) unidos por una aponeurosis y que solo se encuentran en machos sexualmente maduros. Conclusión: Los testículos poseen una organización de tipo lobular irrestricto y la espermatogénesis se da en lóbulos seminíferos. La vejiga natatoria de la Pácora es simple y no tiene estructuras accesorias. La distribución geográfica de P. magdalenae se restringe a la cuenca del río Magdalena en Colombia.

Introduction: The Pácora (Plagioscion magdalenae) is a species native to Colombia and in near-threatened category at the country level, of which little is known about the structures with ethological contribution in its life history. Objective: To analyze the gonadal development related to spermatogenesis of P. magdalenae and the taxonomic implications from the swim bladder. Methods: We collected seven samples in two climatic periods: the first from October 2019 to February 2020 of bimonthly collections, and the second from October 2020 to January 2021 of monthly collections; to cover every moment of the flood pulse of the lower Magdalena basin. We described the testicular histomorphology and macroscopic characteristics of the swim bladder of the species. In addition, we analyzed aspects such as morphometric relationships, size classes by sex, sex ratio and time of sexual maturity. Results: We analyzed 142 specimens and established 4 size intervals (between 145 and 575 mm SL), 66 were males and 73 females with an overall sex ratio of 1.1:0.9 (female-male) with no differences. Males have tubular testes protected by the peritoneum covered by the sonic musculature of the swim bladder, which has a ''carrot'' shape without appendages, with two lateral bands of intrinsic muscles (average between 6.75 cm long and 1.48 cm wide) connected by an aponeurosis and found only in sexually mature males. Conclusion: The testes have an unrestricted lobular organization and spermatogenesis occurs in the seminiferous lobes. The swim bladder of the Pácora is simple and has no accessory structures. The geographic distribution of P. magdalenae is restricted to the Magdalena River basin in Colombia.

Aggressive angiomyxoma of the epididymis: A case report.

BACKGROUND: Aggressive angiomyolipoma is an extremely rare benign mesenchymal tumor that was originally described as a locally recurrent mucinous spindle cell tumour. Aggressive angiomyolipoma originates from myofibroblasts, vascular smooth muscle cells, or fibroblasts, and displays various phenotypes of myofibroblasts and abnormal muscle arteries. Aggressive angiomyolipoma was first identified in 1983 and fewer than 50 male patients have been reported to date. It is an extremely rare mesenchymal tumour and often confused with other diseases. Patients with epididymal aggressive angiomyolipoma lack typical symptoms, most of which occur incidentally, although some patients may experience mild pain, discomfort, and swelling. Pain may be exacerbated by pressure from the mass. CASE SUMMARY: A 66-year-old male was admitted to the hospital on January 14, 2022 with chief complaint of swelling in the left scrotum for one year. There was no apparent cause for the swelling. The patient did not consult with any doctor or receive any treatment for the swelling. The enlarged scrotum increased in size gradually until it reached approximately the size of a goose egg, and was accompanied by discomfort and swelling of the left cavity of the scrotum. The patient had no history of any testicular trauma, infection, or urinary tract infection. The patient urinated freely, 1-2 times at night, without urgency, dysuria (painful urination), or haematuria. There was no significant family history of malignancy. The patient underwent excision of the enlarged tumour and the left epididymis under general anaesthesia on January 18, 2022. Twelve months of follow-up revealed no recurrence. The patient was satisfied with the treatment. CONCLUSION: Aggressive angiomyolipoma is extremely rare clinically and often confused with other diseases. The pathogenesis of aggressive angiomyolipoma is unclear and the clinical presentation is mostly a painless enlarged mass. The diagnosis of aggressive angiomyolipoma requires a combination of medical history, preoperative imaging such as computed tomography and magnetic resonance imaging, cytological examination and preoperative and postoperative pathological biopsy. The preferred treatment is surgery, with the possibility of a new alternative treatment option after hormonal therapy. Aggressive angiomyolipoma should be considered in the differential diagnosis of parametrial tumors of the male genital area that present as clinically significant masses. The high recurrence rate of aggressive angiomyolipoma may be related to incomplete tumor resection, and patients with aggressive angiomyolipoma are advised to undergo annual postoperative follow-up and imaging for recurrence.

Effects of exposure to PM2.5 during pregnancy on the multigenerational reproductive outcomes of male mouse offspring and the role of Sertoli cells.

There is a paucity of studies on the multigenerational reproductive toxicity of fine particle matter (PM2.5) exposure during pregnancy on male offspring and the underlying mechanisms. This study explored the effects of PM2.5 exposure during pregnancy on the spermatogenesis of three consecutive generations of male mouse offspring. We randomized pregnant C57BL/6 mice into the control group, the Quartz Fiber Membrane control group, and two experimental groups exposed to different concentrations of PM2.5 (4.8 and 43.2 mg/kg B.Wt.). Pregnant mice from experimental groups received intratracheal instillation of PM2.5 of different doses on a three-day basis until birth. F1 mature male offspring from PM2.5-exposed pregnant mice were mated with normal female C57BL/6 mice. Likewise, their F2 mature male followed the same to produce the F3 generation. The results showed that PM2.5 exposure during pregnancy led to decreased body and tail length, body weight, and survival rates, decreased sperm concentration and sperm motility, and increased sperm abnormality rates significantly in F1 male offspring. We barely observed significant impacts of PM2.5 on the birth number, survival rates, and index of testes in the F2 and F3 offspring. Further exploration showed that PM2.5 exposure during pregnancy caused the morphological abnormality of Sertoli cells, downregulated androgen receptor (AR) and connexin43, upregulated anti-Müllerian hormone (AMH), cytokeratin-18 (CK-18), caspase-3, and cleaved caspase-3, decreased thyroid-stimulating hormone (TSH) and testosterone (T), and increased triiodothyronine (T3) in F1 male mouse offspring. Overall, we hypothesize that PM2.5 exposure during pregnancy mainly negatively impacts spermatogenesis in the F1 offspring. The possible mechanism could be that PM2.5 exposure during pregnancy disrupts endocrine hormone release in the F1 generation, thereby influencing the maturation and proliferation of their Sertoli cells and hindering spermatogenesis. This study for the first time investigates the role of Sertoli cells in the reproductive toxicity of PM2.5 on offspring.

Auto-immunoproteomics analysis of COVID-19 ICU patients revealed increased levels of autoantibodies related to the male reproductive system.

Background: Coronavirus disease (COVID-19) manifests many clinical symptoms, including an exacerbated immune response and cytokine storm. Autoantibodies in COVID-19 may have severe prodromal effects that are poorly understood. The interaction between these autoantibodies and self-antigens can result in systemic inflammation and organ dysfunction. However, the role of autoantibodies in COVID-19 complications has yet to be fully understood. Methods: The current investigation screened two independent cohorts of 97 COVID-19 patients [discovery (Disc) cohort from Qatar (case = 49 vs. control = 48) and replication (Rep) cohort from New York (case = 48 vs. control = 28)] utilizing high-throughput KoRectly Expressed (KREX) Immunome protein-array technology. Total IgG autoantibody responses were evaluated against 1,318 correctly folded and full-length human proteins. Samples were randomly applied on the precoated microarray slides for 2 h. Cy3-labeled secondary antibodies were used to detect IgG autoantibody response. Slides were scanned at a fixed gain setting using the Agilent fluorescence microarray scanner, generating a 16-bit TIFF file. Group comparisons were performed using a linear model and Fisher's exact test. Differentially expressed proteins were used for KEGG and WIKIpathway annotation to determine pathways in which the proteins of interest were significantly over-represented. Results and conclusion: Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (p ≤ 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients who served as controls. Both cohorts showed substantial similarities (r 2 = 0.73) and exhibited higher autoantibody responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. The sequences for SPANXN4 and STK25 were cross-validated using sequence alignment tools. ELISA and Western blot further verified the autoantigen-autoantibody response of SPANXN4. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19-associated male reproductive tract complications, and warrants further research.

The rare-earth yttrium induces cell apoptosis and autophagy in the male reproductive system through ROS-Ca2+-CamkII/Ampk axis.

China has the world's largest reserves of rare earth elements (REEs), but widespread mining and application of REEs has led to an increased risk of potential pollution. Yttrium (Y), the first heavy REEs to be discovered, poses a substantial threat to human health. Unfortunately, little attention has been given to the impact of Y on human reproductive health. In this study, we investigated the toxic effects of YCl3 on mouse testes and four types of testicular cells, including Sertoli, Leydig, spermatogonial and spermatocyte cells. The results showed that YCl3 exposure causes substantial damage to mouse testes and induces apoptosis and autophagy, but not pyroptosis or necrosis, in testicular cells. Genome-wide gene expression analysis revealed that YCl3 induced significant changes in gene expression, with Ca2+ and mitochondria-related genes being the most significantly altered. Mechanistically, YCl3 exposure induced mitochondrial dysfunction in testicular cells, triggering the overproduction of reactive oxygen species (ROS) by impairing the Nrf2 pathway, regulating downstream Ho-1 target protein expression, and increasing Ca2+ levels to activate the CamkII/Ampk signaling pathway. Blocking ROS production or Ca2+ signaling significantly attenuates apoptosis and autophagy, while supplementation with Ca2+ reverses the suppression of apoptosis and autophagy by ROS blockade in testicular cells. Notably, apoptosis and autophagy induced by YCl3 treatment are independent of each other. Thus, our study suggests that YCl3 may impair the antioxidant stress signaling pathway and activate the calcium pathway through the ROS-Ca2+ axis, which promotes testicular cell apoptosis and autophagy independently, thus inducing testicular damage and impairing male reproductive function.

Anti-fertility effect of Aerva lanata crude extract in male Dams offspring: An experimental study.

Background: Aerva lanata, a herb used as food and also consumed as a tonic by pregnant women to relieve stomach pains and prevent miscarriage. In addition to other characterized properties, it possesses antifertility and anti-implantation activities. Objective: This study investigates the testicular toxicity of the testes of offsprings of Dams treated with crude aqueous extract of Aerva lanata. Materials and Methods: 25 pregnant Wistar rats (Dams) weighing 180-240 gr were randomly earmarked into 5 groups (n = 5/each). Group A served as control; groups B, C, D, and E received 200, 400, 800, and 1000 mg/kg body weight of Aerva lanata extract, respectively, beginning from 12 th to 19 th day of gestation. The pups (delivered of Dams) were weighed, observed, and sacrificed 6 wk post-parturition. The testes of the male pups were obtained for histological procedures the testis histology was examined. Results: No gross malformation was observed in the treatment groups, the number of pups/litter was significantly reduced in group E (p= 0.01), pups weight analysis showed a significant reduction in groups C and E (p= 0.04, and 0.02 respectively), and the mean pup testes weight was significantly reduced in groups B, C, D, and E (p= 0.03, 0.03, 0.01, and < 0.001 respectively) when compared with control. Histologically, the treated pup testes tissues showed varying degrees of disruption and distortion of the cellular arrangements of the germinal epithelium in a dose dependent manner compared to the control. Conclusion: The study revealed a testicular toxicity and possibly antifertility role of Aerva lanata in dams' pups.

Pinostrobin alleviates testicular and spermatological damage induced by polystyrene microplastics in adult albino rats.

BACKGROUND: Polystyrene microplastics (PS-MPs) have become major environmental pollutants that adversely effects multiple organs specifically testicles. Pinostrobin (PN) is an important flavonoid which, shows several pharmacological potentials. PURPOSE: The current study was designed to elucidate the mitigative effects of PN against PS-MPs induced testicular toxicities in rats. METHODS: 48 male albino rats were randomly distributed into 4 groups, control, PS-MPs group (0.01 mg/kg), PS-MPs + PN group (0.01 mg/kg of PS-MPs; 40 mg/kg of PN) and PN group (40 mg/kg). RESULTS: PS-MPs intoxication substantially lessened the activities of glutathione peroxidase (GPx), glutathione reductase (GSR), superoxide dismutase (SOD) along with catalase (CAT) while, raised the level of malondialdehyde (MDA) as well as reactive oxygen species (ROS). Additionally, PS-MPs reduced luteinizing hormone (LH), plasma testosterone, follicle-stimulating hormone (FSH) concentration, sperm motility, sperm count, expression of steroidogenic enzymes and Bcl-2 (anti-apoptotic protein) along with the count of spermatogenic cells. While, dead sperm count, sperm abnormalities (tail, neck and head), Bax and caspase-3 (apoptotic proteins) expression along with histopathological anomalies were elevated. Moreover, PS-MPs exposure increased the level of inflammatory markers. However, PN treatment considerably decreased oxidative stress (OS) by reducing ROS as well as increased sperm motility and alleviated all the damages induced by the PS-MPs. CONCLUSION: Therefore, it is concluded that PN may prove a potential therapeutic candidate to restore all the PS-MPs-induced testicular toxicities.

Cryopreservation modifies the distribution of the prostate-derived lectin SL15 on the llama (Lama glama) sperm.

Lectin-like molecules play a key role in mammalian sperm functionality. These multifunctional proteins have been proven to be involved in sperm capacitation, sperm motility, and viability, formation of the oviductal sperm reservoir, and in sperm-oocyte interaction. In a previous study, we reported the presence of a novel seminal plasma lectin, sperm lectin 15 kDa (SL15), adsorbed to the llama sperm. In order to gain knowledge in the understanding of SL15 and its functions, the aims of this study were to (a) elucidate the presence and localization of SL15 in the llama male reproductive tract and sperm, and (b) determine whether the sperm cryopreservation process of cooling and freeze-thawing affects the SL15 levels and distribution on llama sperm. We found that SL15 protein was expressed along the male reproductive system: testis, epididymis, prostate, and bulbourethral glands, being the prostate the main site of SL15 secretion. SL15 was localized on the sperm head, following different localization patterns. In order to understand if sperm cryopreservation induces modifications in the SL15 adsorption pattern, immunocytochemistry and flow cytometry analysis were carried out on fresh, 24 h cooled, and frozen-thawed sperm. Both cooled and frozen sperm showed particular SL15 patterns, that were not observed in the freshly ejaculated, indicating loss of SL15. Flow cytometry analysis also exhibited a decrease of SL15 in the cooled sperm (P < 0.05), whereas a tendency to decrease was found in frozen-thawed sperm (P < 0.1) when compared with freshly ejaculated sperm. This study extends the knowledge about the SL15 in the llama male physiology and provides evidence that cryopreservation-related techniques disrupt SL15 adsorption to the sperm membrane, possibly affecting sperm functionality and fertility.

Occupational Exposure to Physical and Chemical Risk Factors: A Systematic Review of Reproductive Pathophysiological Effects in Women and Men.

The human reproductive system can be affected by occupational exposure to many physical and chemical risk factors. This study was carried out to review the studies conducted on the issue of the pathophysiological effects of occupational physical and chemical risk factors on the reproductive system of females and males. In this systematic review, the databases such as "Google Scholar," "Pub-Med," "Scopus," and "Web of Science" were used. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020), the studies included in our study were published between 2000 and 2021. In order to extract the required data, all sections of the articles were reviewed. Out of 57 articles we reviewed, 34 articles were related to field studies and 23 articles to clinical studies. Among them, 43 studies dealt with the pathophysiological effects of chemical agents, six studies dealt with the pathophysiological effects of physical factors, and 8 studies dealt with the pathophysiological effects of physicochemical factors on the human reproductive system. Physical (noise, heat, and radiofrequency radiation) and chemical (such as carbamate and organophosphate pesticides, benzene, toluene, xylene, formaldehyde, NO2, CS2, manganese, lead, nickel, and n-hexane) risk factors had pathophysiological effects on the human reproductive system. The presence of these risk factors in the workplace caused damage to the human reproductive system. The rate of these negative pathophysiological effects can be reduced by performing appropriate managerial, technical, and engineering measures in work environments.

Galaxolide and Irgacure 369 are novel environmental androgens.

Endocrine disruptors are environmental chemicals that can interfere with the endocrine system. However, research on endocrine disruptors that interfere with androgen's actions is still limited. The purpose of this study is to use in silico computation, i.e., molecular docking to facilitate the identification of environmental androgens. Computational docking was used to study the binding interactions of environmental/industrial compounds with the three dimensional structure of human androgen receptor (AR). Then reporter assay and cell proliferation assay using AR-expressing LNCaP prostate cancer cells were used to determine their in vitro androgenic activity. Animal studies using immature male rats were also carried out to test their in vivo androgenic activity. Two novel environmental androgens were identified. As a photoinitiator, 2-benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone (Irgacure 369, abbreviated as IC-369) is widely used in the packaging and electronics industries. Galaxolide (HHCB) is widely used in the production of perfume, fabric softeners and detergents. We found that both IC-369 and HHCB could activate AR transcriptional activity and promote cell proliferation in AR-sensitive LNCaP cells. Furthermore, IC-369 and HHCB could induce cell proliferation and histological changes of seminal vesicles in immature rats. RNA sequencing and qPCR analysis showed that androgen-related genes in seminal vesicle tissue were up-regulated by IC-369 and HHCB. In conclusion, IC-369 and HHCB are new environmental androgens that bind AR and induce AR transcriptional activity, thereby exerting toxicological effects on the development of male reproductive organs.

SARS-CoV-2 Infection and the Male Reproductive System: A Brief Review.

Many studies have suggested that SARS-CoV-2, directly or indirectly, can affect the male reproductive system, although the underlined mechanisms have not been completely elucidated yet. The purpose of this review is to provide a summary of the current data concerning the impact of SARS-CoV-2 infection on the male urogenital tract, with a particular emphasis on the testes and male fertility. The main data regarding the morphological alterations in the testes emerged from autoptic studies that revealed interstitial congestion, micro thrombosis, reduction of Sertoli, Leydig, and germinal cells, infiltrated immune cells, and atrophic seminiferous tubules consistent with orchitis. Furthermore, men with severe infection exhibit sperm parameter alterations, together with abnormalities of the hypothalamic-pituitary-testis axis, strongly suggesting that SARS-CoV-2 could increase the risk of male infertility. However, despite the inadequate number of longitudinal studies, spermatogenesis and sex hormone imbalance seem to improve after infection resolution. The yet unresolved question is whether the virus acts in a direct or/and indirect manner, as discordant data related to its presence in the testis and semen have been reported. Regardless of the direct effect, it has been postulated that the cytokine storm and the related local and systemic inflammation could strongly contribute to the onset of testis dysfunction, leading to male infertility. Therefore, multicentric and longitudinal studies involving a large number of patients are needed to understand the real impact of SARS-CoV-2 infection on male reproduction.

Putative adverse outcome pathways of the male reproductive toxicity derived from toxicological studies of perfluoroalkyl acids.

Adverse outcome pathway (AOP) as a conceptual framework is a powerful tool in the field of toxicology to connect seemingly discrete events at different levels of biological organizations into an organized pathway from molecular interactions to whole organism toxicity. Based on numerous toxicological studies, eight AOPs for reproductive toxicity have been endorsed by the Organization for Economic Co-operation and Development (OECD) Task Force on Hazard Assessment. We have conducted a literature survey on the mechanistic studies on male reproductive toxicity of perfluoroalkyl acids (PFAAs), a class of global environmental contaminants with high persistence, bioaccumulation and toxicity. Using the AOP development strategy, five new AOPs for male reproductive toxicity were proposed here, namely (1) changes in membrane permeability leading to reduced sperm motility, (2) disruption of mitochondrial function leading to sperm apoptosis, (3) decreased gonadotropin-releasing hormone (GnRH) expression in hypothalamus leading to reduced testosterone production in male rats, (4) activation of the p38 signaling pathway leading to disruption of BTB in mice, (5) inhibition of p-FAK-Tyr407 activity leading to the destruction of BTB. The molecular initiating events in the proposed AOPs are different from those in the endorsed AOPs, which are either receptor activation or enzyme inhibition. Although some of the AOPs are still incomplete, they can serve as a building block upon which full AOPs can be developed and applied to not only PFAAs but also other chemical toxicants with male reproductive toxicity.