The polyamines are ubiquitous polycationic compounds. Over the past 40 yr, investigation has shown that some of these, namely spermine, spermidine, and putrescine, are essential to male and female reproductive processes and to embryo/fetal development. Indeed, their absence is characterized by infertility and arrest in embryogenesis. Mammals synthesize polyamines de novo from amino acids or import these compounds from the diet. Information collected recently has shown that polyamines are essential regulators of cell growth and gene expression, and they have been implicated in both mitosis and meiosis. In male reproduction, polyamine expression correlates with stages of spermatogenesis, and polyamines appear to function in promoting sperm motility. There is evidence for polyamine involvement in ovarian follicle development and ovulation in female mammals, and polyamine synthesis is required for steroidogenesis in the ovary. Studies of the embryo indicate a polyamine requirement that can be met from maternal sources before implantation, whereas elimination of polyamine synthesis abrogates embryo development at gastrulation. Polyamines play roles in embryo implantation, in decidualization, and in placental formation and function, and polyamine privation during gestation results in intrauterine growth retardation. Emerging information implicates dietary arginine and dietary polyamines as nutritional regulators of fertility. The mechanisms by which polyamines regulate these multiple and diverse processes are not yet well explored; thus, there is fertile ground for further productive investigation.

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Polyamines on the Reproductive Landscape

Introduction: Cyclophosphamide (CP) is an alkylating antineoplastic agent with known toxicity to the male reproductive system.Areas covered: This review summarizes the known mechanisms by which CP ...

The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents

Increases in the survival rate of men treated with chemotherapeutic drugs and their desire to have children precipitate concerns about the effects of these drugs on germ cells. Azoospermia, oligospermia, and infertility are common outcomes resulting from treatment with cyclophosphamide, an alkylating agent. Exposure of male rats to cyclophosphamide results in dose-dependent and time-specific adverse effects on progeny outcome. Elucidation of the effects of chronic low-dose cyclophosphamide treatment on the expression of stress response genes in male germ cells may provide insight into the mechanisms underlying such adverse effects. Male rats were gavaged with saline or cyclophosphamide (6 mg/kg) for 4‐5 wk; pachytene spermatocytes, round spermatids, and elongating spermatids were isolated; RNA was extracted and probed on cDNA arrays containing 216 cDNAs. After saline treatment, 125 stress response genes were expressed in pachytene spermatocytes (57% of genes studied), 122 in round spermatids (56%), and 83 in elongating spermatids (38%). Cyclophosphamide treatment reduced the number of genes detected in all germ cell types. The predominant effect of chronic cyclophosphamide exposure was to decrease the expression level of genes in pachytene spermatocytes (34% of genes studied), round spermatids (29%), and elongating spermatids (4%). In elongating spermatids only, drug treatment increased the expression of 8% of the genes studied. The expression profiles of genes involved in DNA repair, posttranslational modification, and antioxidant defense in male germ cells were altered by chronic cyclophosphamide treatment. We hypothesize that the effects of cyclophosphamide exposure on germ cell gene expression during spermatogenesis may have adverse consequences on male fertility and progeny outcome. gene regulation, spermatid, spermatogenesis, stress, toxicology

Chronic Cyclophosphamide Treatment Alters the Expression of Stress Response Genes in Rat Male Germ Cells

In 50% of all infertility cases, the male is subfertile or infertile, however, the underlying mechanisms are often unknown. Even when assisted reproductive procedures such as in vitro fertilization and intracytoplasmic sperm injection are performed, the causes of male factor infertility frequently remain elusive. Since the overall activity of cells is closely linked to their metabolic capacity, we analyzed a panel of 180 metabolites in human sperm and seminal plasma and elucidated their associations with spermiogram parameters. Therefore, metabolites from a group of 20 healthy donors were investigated using a targeted LC-MS/MS approach. The correlation analyses of the amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and sugars from sperm and seminal plasma with standard spermiogram parameters revealed that metabolites in sperm are closely related to sperm motility, whereas those in seminal plasma are closely related to sperm concentration and morphology. This study provides essential insights into the metabolome of human sperm and seminal plasma and its associations with sperm functions. This metabolomics technique could be a promising screening tool to detect the factors of male infertility in cases where the cause of infertility is unclear.

/pdf/metabolomic-profiling-reveals-correlations-between-3nshq497eu.pdf

Metabolomic profiling reveals correlations between spermiogram parameters and the metabolites present in human spermatozoa and seminal plasma.

BACKGROUND Male infertility is a global health issue caused by a combination of different factors. Specialists generally rely on semen analysis to diagnose male infertility. However, it is known that diagnostic semen analysis fails to identify about 50% of male infertility disorders. Recently, metabolomics has been proven to be a powerful technique for the diagnosis of different diseases. OBJECTIVE To determine whether metabolites could be used as potential biomarkers for the diagnosis of male factor infertility through comparing seminal plasma samples from infertile men with oligoasthenoteratozospermia (OAT) and samples from normozoospermic controls. MATERIALS AND METHODS This study utilized high-resolution 1 H NMR spectroscopy to reveal whether the metabolomic changes of seminal plasma obtained from 31 patients with oligoasthenoteratozospermia (OAT) are different from the ones obtained from 28 normozoospermic controls. RESULTS Multivariate statistical analysis of NMR data concluded that the metabolomic profile of samples from patients with OAT exhibits statistically significant differences when compared to the controls. The differences were based on the metabolites lactate, citrate, lysine, arginine, valine, glutamine, creatinine, α-ketoglutaric acid, spermine, putrescine, and tyrosine. Except the tyrosine, levels of the above metabolites were significantly decreased in patients with OAT compared to the controls. The levels of citrate, choline, spermine, putrescine, α-ketoglutaric acid, valine, and tyrosine were significantly different (p < 5 × 10-4 ) between two groups. On the other hand, levels of lactate, creatinine, lysine, arginine, and glutamine were also statistically significant (0.001 < p < 0.05). However, considering the p-values, the physiological relevance of these metabolites may be lower when compared to the others. A PLS-DA model built on the NMR data achieved 89.29% sensitivity and 93.55% specificity results in a leave-one-out cross-validation process. DISCUSSION AND CONCLUSION 1 H NMR spectroscopy-based metabolomic analysis could be used as a diagnostic tool for the diagnosis of oligoasthenoteratozospermia.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.12707

Metabolomics analysis of seminal plasma in patients with idiopathic Oligoasthenoteratozoospermia using high-resolution NMR spectroscopy.

Polyamine content has been determined in the seminal plasma of unfertile men before and after S-adenosylmethionine treatment. Spermine and spermidine levels in azoospermic patients were found very low (80 and 24 microgram/ml) with respect to normospermic (1500 and 60 microgram/ml): S-adenosylmethionine treatment enhanced polyamine content (50-300%) in oligospermic patients. Furthermore, an increase of sperm count and motility has been observed in these patients.

Savoca S

Papers

Polyamine levels in human semen of unfertile patients: effect of S-adenosylmethionine.