The sperm mitochondrion: Organelle of many functions.

Obesity has grown to pandemic proportions. It affects an increasing number of children, adolescents and young adults exposed to the silent comorbidities of this disorder for a longer period. Infertility has arisen as one important comorbidity associated with the energy dysfunction promoted by obesity. Spermatogenesis is a highly regulated process that is determined by specific energetic requirements. The reproductive potential of males relies on hormonal-dependent and -independent stimuli that control sperm quality. There are conflicting data concerning the impact of male overweight and obesity on sperm quality, as well as on the possible paternal-induced epigenetic trait inheritance of obesity. In addition, it remains a matter of debate whether massive weight loss induced by lifestyle interventions, drugs or bariatric surgery may or may not benefit obese men seeking fatherhood. Herein, we propose to discuss how energy balance may modulate hormonal signalling and sperm quality in overweight and obese men. We also discuss some molecular mechanisms that mediate obesity-related dysfunction in male reproductive system and how paternal obesity may lead to trait inheritance. Finally, we will discuss how lifestyle modifications and sustained weight loss, particularly the loss achieved by bariatric surgery, may revert some of the deleterious effects of obesity in men and their offspring.

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Obesity, energy balance and spermatogenesis.

Subfertility decreases the efficiency of the cattle industry because artificial insemination employs spermatozoa from a single bull to inseminate thousands of cows. Variation in bull fertility has been demonstrated even among those animals exhibiting normal sperm numbers, motility, and morphology. Despite advances in research, molecular and cellular mechanisms underlying the causes of low fertility in some bulls have not been fully elucidated. In this study, we investigated the metabolic profile of bull spermatozoa using non-targeted metabolomics. Statistical analysis and bioinformatic tools were employed to evaluate the metabolic profiles high and low fertility groups. Metabolic pathways associated with the sperm metabolome were also reported. A total of 22 distinct metabolites were detected in spermatozoa from bulls with high fertility (HF) or low fertility (LF) phenotype. The major metabolite classes of bovine sperm were organic acids/derivatives and fatty acids/conjugates. We demonstrated that the abundance ratios of five sperm metabolites were statistically different between HF and LF groups including gamma-aminobutyric acid (GABA), carbamate, benzoic acid, lactic acid, and palmitic acid. Metabolites with different abundances in HF and LF bulls had also VIP scores of greater than 1.5 and AUC- ROC curves of more than 80%. In addition, four metabolic pathways associated with differential metabolites namely alanine, aspartate and glutamate metabolism, β-alanine metabolism, glycolysis or gluconeogenesis, and pyruvate metabolism were also explored. This is the first study aimed at ascertaining the metabolome of spermatozoa from bulls with different fertility phenotype using gas chromatography-mass spectrometry. We identified five metabolites in the two groups of sires and such molecules can be used, in the future, as key indicators of bull fertility.

https://link.springer.com/content/pdf/10.1186/s12864-019-6074-6.pdf

Uncovering sperm metabolome to discover biomarkers for bull fertility

Sperm counts have shown a progressive decline across the world since the mid-1900s. Global rates of obesity have been climbing at a similarly alarming rate, suggesting that these two factors may be linked. However, studies examining the relationship between body mass index (BMI) and male fertility have produced conflicting results. These discrepancies among studies are commonly attributed to limitations that are inherent in human studies such as correlational data and confounding factors-limitations that are absent from animal studies. Hence, we conducted a systematic review and meta-analysis of animal studies that experimentally induced obesity with a high-fat diet and measured impacts on sperm traits and/or male fertility. Overall, we found strong, consistent evidence in animal studies that high-fat diets are detrimental for male fertility. Compared with controls, males fed a high-fat diet had smaller testes and sex accessory glands relative to body size, reduced semen quality, reduced mating success, and reduced fertilization success. This is the first time that experimental data of high-fat diet effects on male reproduction have been synthesized in a meta-analysis, and thus, our results provide novel insight to the complex question of how dietary-induced obesity affects male fertility. The strong negative effects detected in animal models suggest that the inconsistent results plaguing human studies are an artefact of limitations inherent in correlational studies rather than a true effect.

High-fat diets reduce male reproductive success in animal models: A systematic review and meta-analysis.

Spermatozoa have the task to deliver an intact paternal genome to the oocyte and to support a successful embryo development. The high levels of sperm DNA fragmentation (sDF) found in sub-/infertile men threat human reproduction and health of the offspring. Strategies to prevent the onset of this type of sperm damage are extensively sought.sDF can be induced by factors like lifestyle-related habits, diseases, drugs, aging, infections and exposure to pollutants. At the cell level, all these factors induce sperm DNA breaks by three main mechanisms: apoptosis, impairment of sperm chromatin maturation and oxidative stress. Apoptosis and defects in maturation of sperm chromatin appear to act in the testis and account for DNA breaks found in dead ejaculated spermatozoa, whereas oxidative stress is likely inducing sDF during the transit through the male genital tracts and accounting for DNA breaks observed in viable spermatozoa of the ejaculate. Oxidative stress appears to be also the main mechanism responsible for induction of sDF after ejaculation, during in vitro manipulation of spermatozoa. Whether or not mature spermatozoa are able to trigger a cell death program is not yet clarified. In particular, it is not clear whether apoptotic nucleases or reactive oxygen species are responsible for producing DNA breaks in ejaculated mature spermatozoa. Knowledge of the mechanisms inducing sDF is a valuable starting point to define possible therapeutic options that however are still far to be established.

Sperm DNA Fragmentation: Mechanisms of Origin.

Summary
Recent evidences have linked abdominal obesity, insulin resistance, and dyslipidemia to male infertility. Since a defective energy metabolism may play an important role in the impairment of sperm quality, the aim of this study is to investigate the sperm energetic metabolism in rats fed with a high-fat diet, an animal model associated with metabolic syndrome development. Sexually mature male Sprague–Dawley rats were divided into two groups and fed for 4 weeks a standard diet (control group) or a diet enriched in 35% of fat (high fat group). Liver and adipose tissue weight, plasma glucose, insulin, and lipid concentrations were determined. Activities of enzymes involved in sperm energetic metabolism were evaluated by spectrophotometric assays. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption. The administration of a high-fat diet caused a significant increase in body weight of rats and provoked hyperglycemia, hyperinsulinemia, and dyslipidemia. In these animals, we also observed a reduction in sperm concentration and motility. The investigation of sperm energetic metabolism in animals fed a high-fat diet revealed an impairment in the activity of pyruvate and lactate dehydrogenase, citrate synthase, and respiratory chain complexes. A parallel reduction in the cellular levels of adenosine triphosphate (ATP) and an increase in oxidative damage were also observed. A defective energy metabolism may play an important role in the impairment of sperm quality in the high-fat diet fed rats.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/andr.12182

A high-fat diet negatively affects rat sperm mitochondrial respiration

Summary
Recently, obesity has been linked to male infertility. In animal models the administration of a high-fat diet caused a reduction in sperm quality, by impairing gamete energy metabolism. The aim of this study was to investigate a possible effect of dietary fatty acids supplementation in the modulation of sperm energy metabolism and, in turn, in the improvement of sperm quality in rats fed a high-fat diet. Sexually mature male Sprague–Dawley rats were divided into four groups and fed for 4 weeks a standard diet (control group), a high-fat diet (enriched in 35% of fat and 15% sucrose), a high-fat diet supplemented with 2.5% olive oil (a source of monounsaturated fatty acids) or a high-fat diet supplemented with 2.5% krill oil (a source of n-3 polyunsaturated fatty acids). Liver and adipose tissue weight, plasma glucose, insulin and lipid concentrations were determined. Activities of enzymes involved in sperm energetic metabolism were evaluated by spectrophotometric assays. Sperm mitochondrial respiratory efficiency was also assayed. The obtained results suggest that olive oil partially counteracts the negative effects of a high-fat diet on sperm quality, by increasing gamete motility, by reducing oxidative stress and slightly improving mitochondrial respiration efficiency. On the other hand, krill oil determines an increase in sperm concentration and motility, an increase in the activities of lactate dehydrogenase, Krebs cycle enzymes and respiratory chain complexes; a parallel increase in the cellular levels of ATP and a reduction in oxidative damage were also observed. These results suggest that dietary fatty acids are able to positively influence sperm quality and function.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/andr.12348

N. Moscatelli

Papers

A high-fat diet negatively affects rat sperm mitochondrial respiration

Dietary fatty acids influence sperm quality and function.