The environment and male reproductive system: the potential role and underlying mechanisms of cadmium in testis cancer.

Cadmium is a known human carcinogen, and has been shown to profoundly affect male reproductive function, at multiple levels, by exerting both endocrine and non-endocrine actions. Nevertheless, the potential role of cadmium in the etiology of testis cancer has been scantly investigated in humans, and, currently, available epidemiological observational studies are insufficient to draw definitive conclusions in this regard. On the contrary, experimental studies in laboratory animals demonstrated that cadmium is a strong inducer of testis tumors, mostly represented by benign Leydig cell adenoma; moreover, malignant transformation was also reported in few animals, following cadmium treatment. Early experimental studies in animals proposed an endocrine-dependent mechanism of cadmium-induced testis tumorigenesis; however, more recent findings from cell-free assays, in vitro studies, and short-term in vivo studies, highlighted that cadmium might also contribute to testis tumor development by early occurring endocrine-independent mechanisms, which include aberrant gene expression within the testis, and genotoxic effects, and take place well before the timing of testis tumorigenesis. These endocrine-independent mechanisms, however, have not been directly investigated on testis tumor samples retrieved from affected, cadmium-treated animals so far. The present review focuses on the relationship between cadmium exposure and testis cancer, by reporting the few epidemiological observational human studies available, and by providing animal-based experimental evidences of cadmium implication in the pathogenesis and progression of testis tumor. Moreover, the relevance of experimental animal studies to human cadmium exposure and the translational potential of experimental findings will be extensively discussed, by critically addressing strengths and weaknesses of available data.

Seminal cadmium affects human sperm motility through stable binding to the cell membrane.

Environmental pollutants are claimed to be major factors involved in the progressive decline of the fertility rate worldwide. Exposure to the heavy metal Cadmium (Cd) has been associated with reproductive toxicity due to its ionic mimicry. However, the possible direct accumulation of Cd in human sperm cells has been poorly investigated. In this study, we aimed to clarify the possible direct effect of Cd exposure on sperm function through the analysis of its cell accumulation. Semen samples from 30 male subjects residing in high environmental impact areas and adhering to the "Exposoma e Plurifocalità nella Prevenzione Oncologica" campaign for testis cancer prevention were compared with semen samples from 15 males residing in low exposure areas. Semen levels and cell Cd content were quantified by inductively coupled plasma (ICP) spectroscopy. Cell Cd distribution was assessed by scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS). The impact of Cd on sperm function was evaluated by the in vitro exposure to the heavy metal, whilst possible scavenging approaches/agents were assessed. In addition to higher values of semen Cd, exposed subjects showed a reduction in total motile sperm fraction compared to not-exposed controls (59.6% ± 13.6% vs. 66.3% ± 7.3%, p = 0.037). Semen Cd levels were also significantly correlated with SEM-EDS signals of Cd detected on the head and neck of sperm (respectively p = 0.738, p < 0.001 and ρ = 0.465, p < 0.001). A total of 2 h of in vitro exposure to 0.5 µM Cd was associated with a significant reduction of sperm progressive motility. Scavenging approaches with either hypo-osmotic swelling or 10 µM reduced glutathione were ineffective in blunting cell Cd and restoring motility. The reduction of exposure levels appears to be the main approach to reducing the reproductive issues associated with Cd.

Characterization of telomere length in Agerolese cattle breed, correlating blood and milk samples.

Studies into telomere length in cattle are relatively recent and have focused mainly on the Holstein Friesian cattle breed, making it arduous to evaluate the correlation with ageing due to the early age of culling in this breed. Telomere length provides information about the productive lifespan and the quality of farm management, complying with the 'One Health' approach. This study evaluated telomere length in Agerolese cattle, an autochthonous dairy breed characterized by a long productive lifespan (13 years). Multiplex quantitative PCR estimated telomere length in DNA extracted from blood and milk matrices. Interestingly, the results showed longer telomeres in Agerolese (compared to the Holstein Friesian cattle control group), with a negative correlation between telomere length and increasing age and a synchronous trend between blood and milk samples, with a positive correlation between them.

Sperm Global DNA Methylation (SGDM) in Semen of Healthy Dogs.

Male infertility is an emerging problem in both humans and animals, and the knowledge of its causes is the first step to identifying new diagnostic and therapeutic strategies. In humans, alteration of sperm DNA methylation have been related to poor quality semen, impaired seminal parameters, azoospermia and reduced fertility. Although semen analysis is routinely used to evaluate the male reproductive potential in the canine species, no authors have attempted to relate semen characteristics to the sperm global DNA methylation (SGDM). The aim of this study was to evaluate the SGDM level in healthy dogs and to correlate it with semen parameters that are currently used in dog semen analyses. Conventional and unconventional (sperm DNA fragmentation and SGDM) seminal parameters of thirty dogs from different breeds were evaluated. A positive correlation was found between SGDM and sperm concentration (r = 0.41; p < 0.05), and total sperm count (r = 0.61; p < 0.001); SGDM was significantly lower in oligozoospermic vs non-oligozoospermic dogs (4.3% vs. 8.7%; p < 0.005). Our findings suggest that SGDM levels are related to conventional seminal parameters, and could be used as a marker of testis function and spermatogenesis in dogs.

DNA fragmentation and morphometric studies in sperm of stallions supplemented with maca (Lepidium meyenii).

The reproductive performances of livestock play an essential role in the economic management of the farm. The improvement of semen quantity and quality through the use of food supplements that lack substances which are forbidden in animal feeding, or that may have detrimental effects, is an important goal. Maca (Lepidium meyenii) is a plant that has been used for centuries in the Andes for nutrition and fertility enhancement in humans and animals. The aim of this study was to evaluate the effects of food supplementation of stallions with maca during the breeding season on spermatozoa parameters such as DNA fragmentation and shape, which are two predictive indexes of spermatozoa functionality. For this purpose, ejaculate volume, semen gel-free volume, sperm concentration and motility, total sperm count, sperm DNA fragmentation and sperm head parameters (length, width, perimeter, area, shape factor, roughness) were measured in four stallions. Maca food supplementation in stallions during breeding reduced the percentage of spermatozoa with fragmented DNA, increased significantly sperm concentration and exerted an elongation of the spermatozoa head, a condition that is believed to improve spermatozoa functionality, suggesting that food supplementation of maca could be useful in horse breeding during the breeding season.

Cytogenetic Analyses in Ewes with Congenital Abnormalities of the Genital Apparatus.

The Disorders of Sex Development (DSDs) are congenital conditions characterized by inconsistency among chromosomal, gonadal, and anatomical sex development. The aim of this research is to report the clinical and cytogenetic findings of four DSD cases and 13 couples of heterosexual twins in sheep. To this purpose, C- and R-banding techniques were used, and the analyses of the SRY (Sex Determining Region Y) and AMEL (Amelogenin) genes were carried out. Moreover, morphopathological analyses were performed in one case. The four DSD sheep cases were registered as females at birth, and for none of them it was possible to establish whether the subjects were born from heterosexual multiple births. Three of the four cases were diagnosed as XX/XY blood lymphocyte chimaeras, while the fourth case was diagnosed as a 54, XY SRY-positive DSD sheep. None of the heterosexual twins showed XX/XY blood chimaerism. This finding suggests that the blood chimaeric cases detected could also be due to a zygote/embryo fusion. Moreover, no gene variants involved in sheep DSD are known, the identification of which would be very useful for the sheep industry.

"Bisphenol a: an emerging threat to male fertility".

BACKGROUND: Among the factors causing male infertility, one of the most debated is the exposure to environmental contaminants. Recently, the chemical compound Bisphenol A (BPA) has drawn attention from the reproductive science community, due to its ubiquitous presence in day-to-day life. Its toxic action appears to mainly affect the male reproductive system, directly impacting male fertility. MAIN: The purpose of this review is to investigate current research data on BPA, providing an overview of the findings obtained from studies in animal and human models, as well as on its supposed mechanisms of action. CONCLUSION: A clear understanding of BPA action mechanisms, as well as the presumed risks deriving from its exposure, is becoming crucial to preserve male fertility. The development and validation of methodologies to detect BPA toxic effects on reproductive organs can provide greater awareness of the potential threat that this chemical represents.

The role of vitamin D in male fertility: A focus on the testis.

In the last decade, vitamin D has emerged as a pleiotropic molecule with a multitude of autocrine, paracrine and endocrine functions, mediated by classical genomic as well as non-classical non-genomic actions, on multiple target organs and systems. The expression of vitamin D receptor and vitamin D metabolizing enzymes in male reproductive system, particularly in the testis, suggests the occurrence of vitamin D synthesis and regulation as well as function in the testis. The role of vitamin D in the modulation of testis functions, including hormone production and spermatogenesis, has been investigated in animals and humans. Experimental studies support a beneficial effect of vitamin D on male fertility, by modulating hormone production through genomic and non-genomic actions, and, particularly, by improving semen quality essentially through non-genomic actions. However, clinical studies in humans are controversial. Indeed, vitamin D seems to contribute to the modulation of the bioavailable rather than total testosterone. Moreover, although an increased prevalence or risk for testosterone deficiency was reported in men with vitamin D deficiency in observational studies, the majority of interventional studies demonstrated the lack of effect of vitamin D supplementation on circulating levels of testosterone. The most consistent effect of vitamin D was reported on semen quality. Indeed, vitamin D was shown to be positively associated to sperm motility, and to exert direct actions on spermatozoa, including non-genomic driven modulation of intracellular calcium homeostasis and activation of molecular pathways involved in sperm motility, capacitation and acrosome reaction. The current review provides a summary of current knowledge on the role of vitamin D in male fertility, by reporting clinical and experimental studies in humans and animals addressing the relationship between vitamin D and testis function.