Alpha-lipoic acid improves sperm motility in infertile men after varicocelectomy: a triple-blind randomized controlled trial.

RESEARCH QUESTION: Does supplementation with alpha-lipoic acid (ALA) enhance sperm parameters and/or the status of sperm lipid peroxidation and DNA fragmentation in men who have undergone microsurgical repair of a varicocele? DESIGN: Individuals with a varicocele who had undergone varicocelectomy were divided into two groups receiving either 600 mg of ALA or an identical placebo for 80 days. Semen samples obtained from the participants before surgery and after completion of the course of medication were analysed and compared. Participants, clinicians and data analysts were blinded to the randomization sequence. RESULTS: In the ALA group, total motility (P = 0.01) and progressive motility (P = 0.002) of the spermatozoa were significantly higher compared with the placebo group after surgery. Sperm lipid peroxidation and DNA damage (assessed by sperm chromatin structure assay) showed significant decreases in both the ALA and placebo groups (P ≤ 0.02) after treatment. CONCLUSIONS: An 80-day course of ALA medication after surgical repair improves total motility and progressive motility of the spermatozoa in individuals with a varicocele.

Body mass index and age correlate with antioxidant supplementation effects on sperm quality: Post hoc analyses from a double-blind placebo-controlled trial.

Spermatozoa are vulnerable to lack of energy and oxidative stress as a result of elevated levels of reactive oxygen species. Therefore, it is essential that appropriate nutrients are available during maturation. This randomised, double-blind, placebo-controlled trial investigated the effect of 6-month supplementation with carnitines and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. Semen analyses were done at the beginning and end of the treatment. In addition to main analyses, post hoc analyses for age and body mass index (BMI) were carried out. Results were interpreted by dividing the population into two age and BMI classes. In 94 patients who completed the study, all sperm parameters increased in supplemented patients compared to the placebo group. A significant (p = .0272) difference in supplementation efficacy was observed for total motility on patients with varicocele and BMI < 25. In the same group, also the progressive motility was significantly superior (p = .0159). For Responder analysis, total motility results were confirmed in both the cited group (p = .0066) and in the varicocele group with BMI < 25 and age < 35 (p = .0078). This study suggests that supplementation is more effective in subjects with varicocele younger than 35 years with BMI < 25.

The effects of lycopene supplement on the spermatogram and seminal oxidative stress in infertile men: A randomized, double-blind, placebo-controlled clinical trial.

Infertility is a major, worldwide problem that is affected, and mediated, by several factors, in particular, oxidative stress. Thus, the aim of this study was to evaluate the effect of lycopene supplementation on spermatogram and seminal oxidative stress. In this randomized, double-blind, placebo-controlled trial study, 44 infertile men with oligozoospermia were randomly divided into two groups: The experimental group was supplemented with 25 mg of lycopene, and the control group received placebo for 12 weeks. Anthropometric, physical activity and dietary assessment, semen analysis, total antioxidant capacity (TAC), malondialdehyde, and glutathione peroxidase were measured pre- and post-intervention. At the end of the study, there was a significant increase in total sperm count and concentration in the lycopene group, and the latter total count remained significant after adjustment (p < .05). Intragroup analysis showed a significant increase in ejaculate volume, total sperm count, concentration total motility, nonprogressive, and nonmotility in lycopene group (p < .05). The TAC changes, in both groups, remained significant after adjustment (p < .05). Also, within-group analysis showed a significant increase in TAC levels (p < .05). Lycopene supplement can improve sperm parameters and oxidative stress biomarkers in oligozoospermia infertile men; however, further studies with larger sample size and duration are required.

Hypospermia Improvement in Dogs Fed on a Nutraceutical Diet.

Male dog infertility may represent a serious concern in the canine breeding market. The aim of this clinical evaluation was to test the efficacy of a commercially available nutraceutical diet, enriched with Lepidium meyenii, Tribulus terrestris, L-carnitine, zinc, omega-3 (N-3) fatty acids, beta-carotene, vitamin E, and folic acid, in 28 male dogs suffering from infertility associated with hypospermia. All dogs received the diet over a period of 100 days. At the end of the evaluation period, no adverse effects, including head and tail anomalies percentage onset, were reported. Interestingly, motility percentage, semen volume and concentration, and total number of sperms per ejaculation significantly increased. Further investigations on a wider cohort of dogs might be useful to better correlate the presence of oxytetracycline in pet's diet and the onset of infertility and clearly assess the action mechanism of an oxytetracycline-free nutraceutical diet.

White tea consumption restores sperm quality in prediabetic rats preventing testicular oxidative damage.

Prediabetes represents a major risk factor for the development of type 2 diabetes mellitus (T2DM). It encompasses some, but not all, T2DM diagnostic criteria. Prediabetes has been recently associated with altered testicular function and increased testicular oxidative stress (OS). Tea is widely consumed and its anti-hyperglycaemic/antioxidant properties are known. This study aimed to evaluate whether white tea (WTEA) consumption by prediabetic rats could prevent testicular OS, preserving sperm quality. For that purpose, WTEA (presenting a high catechin content) was given to 30-day-old streptozotocin-induced prediabetic rats for 2 months. Testicular antioxidant potential and OS were evaluated, as well as sperm parameters, by standard techniques. WTEA consumption improved glucose tolerance and insulin sensitivity in prediabetic rats. Testicular antioxidant potential was increased by WTEA consumption, restoring protein oxidation and lipid peroxidation, although glutathione content and redox state were not altered. WTEA consumption improved sperm concentration and sperm quality (motility, viability and abnormality) was restored. Overall, WTEA consumption improved reproductive health of male prediabetic rats. Based on the study results, WTEA consumption appears to be a natural, economical and effective strategy to counteract the deleterious effects of prediabetes on male reproductive health, but further studies will be needed before a definitive recommendation is made.

The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report.

BACKGROUND: Sperm chromatin structure is often impaired; mainly due to oxidative damage. Antioxidant treatments do not consistently produce fertility improvements and, when given at high doses, they might block essential oxidative processes such as chromatin compaction. This study was intended to assess the effect on male sub-fertility of a pure one carbon cycle nutritional support without strong antioxidants. METHODS: Male partners of couples resistant to at least 2 assisted reproductive technology (ART) attempts, with no evidence of organic causes of infertility and with either DNA fragmentation index (DFI) measured by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) or nuclear decondensation index (SDI) measured by aniline blue staining exceeding 20%, were invited to take part in a trial of a nutritional support in preparation for a further ART attempt. The treatment consisted of a combination of B vitamins, zinc, a proprietary opuntia fig extract and small amounts of N-acetyl-cysteine and Vitamin E (Condensyl™), all effectors of the one carbon cycle. RESULTS: 84 patients were enrolled, they took 1 or 2 Condensyl™ tablets per day for 2 to 12 months. Positive response rates were 64.3% for SDI, 71.4% for DFI and 47.6% for both SDI and DFI. Eighteen couples (21%) experienced a spontaneous pregnancy before the planned ART cycle, all ended with a live birth. The remaining 66 couples underwent a new ART attempt (4 IUI; 18 IVF; 44 ICSI) resulting in 22 further clinical pregnancies and 15 live births. The clinical pregnancy rate (CPR) and the live birth rate (LBR) were 47.6% and 39.3% respectively. The full responders, i.e. the 40 patients achieving an improvement of both SDI and DFI, reported a CPR of 70% and a LBR of 57.5% (p<0.001). CONCLUSIONS: Nutritional support of the one carbon cycle without strong antioxidants improves both the SDI and the DFI in ART resistant male partners and results in high pregnancy rates suggesting a positive effect on their fertility potential.

Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility.

DNA fragmentation is an important factor in the aetiology of male infertility. However, it is still underevaluated and its inclusion in routine semen analysis is debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. Couples may be counselled to proceed directly to intracytoplasmic sperm injection as it is more successful in this group, avoiding costly procedures, recurrent failures or pregnancy losses; however, this treatment is not without limitations or risks. Ideally DNA fragmentation should be minimized where possible. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed, and in many cases are shown to be easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential functions, including fertilization. Reducing oxidative stress may improve a couple's chances of conception either naturally or via assisted reproduction. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible. DNA fragmentation is an important factor in the aetiology of male infertility. However it is still underevaluated and its inclusion in routine semen analysis is still debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high levels of DNA fragmentation will have significantly lower odds of conceiving naturally or through procedures such as intrauterine insemination and IVF. Intracytoplasmic sperm injection (ICSI) may be much more successful in this group, and couples may be counselled to proceed directly to ICSI, avoiding costly procedures, recurrent failures or pregnancy losses. However, ICSI is not without its limitations or risks. Ideally, DNA fragmentation should be investigated and minimized where possible in men trying to conceive naturally or through assisted reproduction technology. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed and in many cases are easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential sperm function, including fertilization. Reducing oxidative stress may improve a couple's chances of conception either naturally or via assisted reproduction treatment. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible.

[Verification of the effectiveness of the dietary supplementation in infertility treatment]. / Ocena skutecznosci suplementacji zywieniowej w terapii nieplodnosci.

UNLABELLED: Fertility problems are observed in a growing number of couples in many countries, including Poland. The treatment of infertile couple should be comprehensive and apart from medical procedures also other factors affecting fertility potential should be taken into account. There is increasing evidence that a properly balanced diet and/or administration of specifically composed supplements may increase the chances of conceiving both naturally as well as in result of assisted reproductive techniques. THE AIM OF STUDY: Preliminary verification of the effectiveness of vitamin preparation to improve the quality of semen and the number of pregnancies achieved. MATERIAL AND METHODS: In total 28 infertile couples were included to the study. Within 6 months from the start of diet supplementation seminological studies and the assessment of getting pregnant have been conducted. RESULTS: The consumption of vitamin and mineral ingredients improves sperm quality and increases pregnancy rate. CONCLUSIONS: Dietary supplement may help to conceive by increasing the number and improving sperm motility.

Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function.

Male obesity is associated with reduced sperm motility and morphology and increased sperm DNA damage and oxidative stress; however, the reversibility of these phenotypes has never been studied. Therefore, the aim of this study was to assess the reversibility of obesity and its associated sperm physiology and function in mice in response to weight loss through diet and exercise. C57BL6 male mice (n = 40) were fed either a control diet (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 10 wk before allocation to either diet and/or swimming exercise interventions for 8 wk. Diet alone reduced adiposity (1.6-fold) and serum cholesterol levels (1.7-fold, P < 0.05), while exercise alone did not alter these, but exercise plus diet also improved glucose tolerance (1.3-fold, P < 0.05). Diet and/or exercise improved sperm motility (1.2-fold) and morphology (1.1-fold, P < 0.05), and reduced sperm DNA damage (1.5-fold), reactive oxygen species (1.1-fold), and mitochondrial membrane potential (1.2-fold, P < 0.05) and increased sperm binding (1.4-fold) (P < 0.05). Sperm parameters were highly correlated with measures of glycemia, insulin action, and serum cholesterol (all P < 0.05) regardless of adiposity or intervention, suggesting a link between systemic metabolic status and sperm function. This is the first study to show that the abnormal sperm physiology resulting from obesity can be reversed through diet and exercise, even in the presence of ongoing obesity, suggesting that diet and lifestyle interventions could be a combined approach to target subfertility in overweight and obese men.

Epigenetics and its role in male infertility.

Male infertility is a common and complex problem affecting 1 in 20 men. Despite voluminous research in this field, in many cases, the underlying causes are unknown. Epigenetic factors play an important role in male infertility and these have been studied extensively. Epigenetic modifications control a number of processes within the body, but this review will concentrate on male fertility and the consequences of aberrant epigenetic regulation/modification. Many recent studies have identified altered epigenetic profiles in sperm from men with oligozoospermia and oligoasthenoteratozoospermia. During gametogenesis and germ cell maturation, germ cells undergo extensive epigenetic reprogramming that involves the establishment of sex-specific patterns in the sperm and oocytes. Increasing evidence suggests that genetic and environmental factors can have negative effects on epigenetic processes controlling implantation, placentation and fetal growth. This review provides an overview of the epigenetic processes (histone-to-protamine exchange and epigenetic reprogramming post-fertilization), aberrant epigenetic reprogramming and its association with fertility, possible risks for ART techniques, testicular cancer and the effect of environmental factors on the epigenetic processes.

The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST).

OBJECTIVE: To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns. DESIGN: A multicenter, double-blind, block randomized, placebo-controlled trial titled "The Folic Acid and Zinc Supplementation Trial (FAZST)." SETTING: Infertility care centers. PATIENT(S): Male partners (18 years and older) from heterosexual couples (female partners aged 18-45 years) seeking fertility treatment were recruited. INTERVENTION(S): Men were randomized 1:1 to receive folic acid (5 mg) and elemental zinc (30 mg) (n = 713) or a matching placebo (n = 757) daily for 6 months. MAIN OUTCOME MEASURE(S): Sperm DNA methylation was analyzed using the EPIC methylation array (Illumina) at 6 months. Differential sperm DNA methylation was assessed at multiple levels (regional, single cytosine phosphate guanine, etc.). We additionally assessed the impact of supplementation on epigenetic age. RESULT(S): No significant differences were identified between the treatment and placebo groups although some trends appeared to be present. To determine if these trends were noteworthy, we implemented various permutations and found that the patterns we identified were no more than would be expected by random chance. CONCLUSION(S): The data presented here strongly suggest that this supplementation regimen is not effective at altering sperm DNA methylation. These data comport well with previous findings from the FAZST study that found no impact of supplementation on basic semen analysis parameters or live birth. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01857310.

Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men.

CONTEXT: Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. OBJECTIVE: This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. METHODS: A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported. RESULTS: Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group. CONCLUSION: High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.

Exploring the potential impact of nutritionally actionable genetic polymorphisms on idiopathic male infertility: a review of current evidence.

Infertility affects about 15% of the world's population. In 40%-50% of infertile couples, a male factor underlies the problem, but in about 50% of these cases, the etiology of male infertility remains unexplained. Some clinical data show that lifestyle interventions may contribute to male reproductive health. Cessation of unhealthy habits is suggested for preserving male fertility; there is growing evidence that most preexisting comorbidities, such as obesity and metabolic syndrome, are highly likely to have an impact on male fertility. The analysis of genetic polymorphisms implicated in metabolic activity represents one of the most exciting areas in the study of genetic causes of male infertility. Although these polymorphisms are not directly connected with male infertility, they may have a role in specific conditions associated with it, that is, metabolic disorders and oxidative stress pathway genes that are potentially associated with an increased risk of male infertility due to DNA and cell membrane damage. Some studies have examined the impact of individual genetic differences and gene-diet interactions on male infertility, but their results have not been synthesized. We review the current research to identify genetic variants that could be tested to improve the chances of conceiving spontaneously through personalized diet and/or oral vitamin and mineral supplementation, by examining the science of genetic modifiers of dietary factors that affect nutritional status and male fertility.

Treatment With Cholecalciferol Leads to Increase Of Selected Semen Parameters in Young Infertile Males: Results of a 6-month Interventional Study.

High incidence of infertility along with low vitamin D levels was detected in otherwise healthy young men. The aim is to observe the effect of vitamin D supplementation on semen parameters as assessed by semen analysis in infertile men. In total, 45 men (mean age 36.6 years) in consecutive order were included, of whom 34 finished the study. Subjects were supplemented by vitamin D (cholecalciferol) 2500 IU/day. Vitamin D levels were assessed by HPLC. Semen analysis was performed strictly following 2010 WHO guidelines. Study periods were baseline and month 6. During follow-up, 20 %, 7.4 %, 22 % and 0.7 % increase in serum vitamin D levels, progressive sperm motility, sperm concentration and sperm morphology, respectively, were observed (all p<0.05). At follow-up end, 9 patients (26 %) reached normal sperm parameters of whom 2 fertilized their partner. There was no correlation between vitamin D and semen parameters observed. This study proves that vitamin D supplementation is possibly a modulator of sperm parameters in vitamin D deficient, otherwise healthy men. Although a direct relationship between vitamin D and sperm parameters was not observed obtaining adequate vitamin D levels could likely play a role in the male factor of infertility.

SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility.

Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid ß-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. We demonstrate that Slc22a14-mediated FAO is essential for spermatozoa energy generation and motility. Furthermore, sperm from wild-type mice treated with a riboflavin-deficient diet mimics those in Slc22a14 knockout mice, confirming that an altered riboflavin level causes spermatozoa morphological and bioenergetic defects. Beyond substantially advancing our understanding of spermatozoa energy metabolism, our study provides an attractive target for the development of male contraceptives.

Dietary supplementation with a novel l-carnitine multi-micronutrient in idiopathic male subfertility involving oligo-, astheno-, teratozoospermia: A randomized clinical study.

OBJECTIVE: To study the influence of a multi-component nutrient dietary supplement on sperm parameters and pregnancy rates in idiopathic male infertility (IMI) with oligo-, astheno-, and teratozoospermia. DESIGN: A randomized, double-blind, placebo-controlled, prospective, parallel arms (1:1 allocation ratio), multi-center clinical trial. SETTINGS: Eight urology/reproductive health clinical centers located in Ukraine. PATIENTS: Eighty-three males aged 21-50 years with IMI and at least 1 of 3 abnormal values: total sperm concentration < 15 million/ml or/and spermatozoa progressive motility < 32% or/and forms with normal morphology < 4%. INTERVENTION(S): Patients were randomly allocated verum test dietary supplement (TDS) containing l-carnitine/acetyl-l-carnitine, l-arginine, glutathione, co-enzyme Q10, zinc, vitamin B9 , vitamin B12 , selenium, or placebo 1 time daily for 6 months. MAIN OUTCOME(S): The primary outcome measure was the percentage of normal spermiograms (concentration ≥ 15 million/ml and ≥ 32% of spermatozoa with progressive motility and ≥ 4% of normal forms) at month 0, 2, and 4. The percentage of pregnancies served the secondary outcome endpoint. Differences between the groups were assessed in z-test for proportions. RESULTS: All males finished the study. At month 4, 29/42 (69.0%) males in the verum and 9/41 (22.0%) had normal spermiograms (P < .001). The percentage of spontaneous pregnancies in the verum group was greater than in the placebo group (10/42, 23.8% vs. 2/41, 4.9%, respectively, P = .017). There were no reportable supplement-associated adverse events. CONCLUSION: Specific multi-nutrient combination l-carnitine/l-acetyl-carnitine, l-arginine, glutathione, co-enzyme-Q, zinc, folic acid, cyanocobalamin, and selenium can improve sperm quality in males with IMI and increase pregnancy rates.

Phytoestrogen intake and other dietary risk factors for low motile sperm count and poor sperm morphology.

BACKGROUND: Few potentially modifiable risk factors of male infertility have been identified, and while different diets and food groups have been associated with male infertility, evidence linking dietary factors including phytoestrogens and semen quality is limited and contradictory. OBJECTIVES: To study the associations between phytoestrogen intake and other dietary factors and semen quality. MATERIALS AND METHODS: A case-referent study was undertaken of the male partners, of couples attempting conception with unprotected intercourse for 12 months or more without success, recruited from 14 UK assisted reproduction clinics. A total of 1907 participants completed occupational, lifestyle and dietary questionnaires before semen quality (concentration, motility and morphology) were assessed. Food intake was estimated by a 65-item food frequency questionnaire (FFQ) covering the 12 months prior to recruitment. Analyses of dietary risk factors for low motile sperm concentration (MSC: <4.8 × 106 /mL) and poor sperm morphology (PM: <4% normal morphology) used unconditional logistic regression, accounting for clustering of subjects within the clinics, first without, and then with, adjustment for confounders associated with that outcome. RESULTS: High consumption of daidzein (≥13.74 µg/d), a phytoestrogen found in soy products, was a protective factor for MSC with an odds ratio (95%CI) of 0.58 (0.42-0.82) after adjustment for clustering and potential confounding. Dietary risk factors for PM after similar adjustment showed that drinking whole milk (OR 0.67, 95%CI 0.47-0.96) and eating red meat were protective with an OR 0.67 (0.46-0.99) for eating red meat >3 times/wk. DISCUSSION: In this case-referent study of men attending an infertility clinic for fertility diagnosis, we have identified that low MSC is inversely associated with daidzein intake. In contrast, daidzein intake was not associated with PM but eating red milk and drinking whole milk were protective. CONCLUSIONS: Dietary factors associated with semen quality were identified, suggesting that male fertility might be improved by dietary changes.

Antioxidants and sperm DNA damage: a clinical perspective.

PURPOSE: Infertile men possess substantially more sperm DNA damage than do fertile men, damage that may impact negatively on reproductive outcomes. In this era of assisted reproductive technologies there is mounting concern regarding the safety of utilizing DNA-damaged spermatozoa in this setting. Therefore, it is important to identify strategies that may reduce sperm DNA damage. The purpose of this review is to discuss the rationale for antioxidant therapy in men with sperm DNA damage and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm DNA damage. METHODS: We reviewed the literature on antioxidants and sperm DNA damage. RESULTS: To date, the data suggest that dietary antioxidants may be beneficial in reducing sperm DNA damage, particularly, in men with high levels of DNA fragmentation. However, the mechanism of action of dietary antioxidants has not been established and most of the clinical studies are small. A beneficial effect of in vitro antioxidant supplements in protecting sperm DNA from exogenous oxidants has been demonstrated, however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established.

Effect of Dietary n-3 Source on Rabbit Male Reproduction.

In the last two decades, the human sperm count linearly decreased in Western countries. Health problems, lifestyle, pollutants, and dietary behaviours are considered as the main risk factors, and the unbalance of dietary n-6/n-3 fatty acids is one of the most relevant. The aim of the present research is to study the effect of different dietary sources of n-3 polyunsaturated fatty acids (PUFA) on reproductive traits using rabbit buck as the animal model. Fifteen rabbit bucks were assigned to three experimental groups: the control group, the FLAX group fed 10% extruded flaxseed, and the FISH group fed 3.5% fish oil for 110 days (50-day adaptation and 60-day experimental periods). Semen samples were collected weekly, whereas blood was collected every two weeks for the analytical determination of semen traits, oxidative status, fatty acid profiles, isoprostanes, neuroprostanes, and the immunocytochemistry of docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) acid. At the end of the trial, the rabbits were killed and the testes were removed and stored for the analysis of fatty acid profile and immunocytochemistry. Results showed that dietary administration of n-3 PUFA improved the track speed of the sperm and increased the n-3 long-chain PUFA mainly confined in the sperm tail. Seminal plasma increased the thiobarbituric reactive substances (TBARs) by three times in the groups fed supplemental n-3, whereas the F2-isoprotanes (F2-IsoPs) and F4-neuroprostanes (F4-NeuroPs) were lower and higher, respectively, in both supplemented groups than in the control. The testes and sperm showed a higher DHA and EPA distribution in rabbits from the n-3 supplemented groups compared with the control. In conclusion, supplemental dietary n-3 PUFA improved sperm motion traits and resulted in an enrichment of membrane fatty acid in the sperm and testes of the rabbits. However, such an increased amount of PUFA negatively affected the sperm oxidative status, which was mainly correlated with the generation of F4-NeuroPs with respect to F2-IsoPs. Accordingly, the latter cannot be considered a good marker of oxidation when diets rich in n-3 PUFA are provided.