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BACKGROUND The medicinal herb fenugreek (Trigonella foenum-graecum) seeds, fortified with dietary fibers and furostanolic saponins including protodioscin, have demonstrated a significant contribution to human health. In our laboratories, Furosap®, a patented 20% protodioscin-enriched extract was developed from fenugreek seeds. OBJECTIVE In an open-label, one-arm, single-center longitudinal study, we examined the safety and efficacy of Furosap® on free and total testosterone levels, fasting blood sugar, blood pressure, sperm count, motility and morphology, dihydroepiandrosterone sulfate (DHEA-S), sexual health, reflex erection, mood alleviation, mental alertness, and total blood chemistry analyses over a period of 12 weeks in healthy male volunteers. METHODS Institutional Ethics Committee approvals and Clinicaltrials.gov registration were obtained. Effect of Furosap® (500 mg/day) was examined of free and total testosterone levels, sperm count, motility and morphology, sexual health, mood and mental alertness, and total blood chemistry analyses in 100 healthy volunteers (age 35-60 Y) over a period of 12 consecutive weeks. RESULTS No changes were observed in body weight and BMI. Both systolic and diastolic blood pressure, and DHEA levels significantly decreased. Free and bound testosterone levels improved significantly at 12 weeks of treatment. Sperm motility significantly increased at 8- and 12-weeks of treatment, while abnormal sperm morphology significantly decreased at 12-weeks of treatment. Mental alertness, mood, and reflex erection score significantly alleviated. An age-induced increasing effect was observed. Furthermore, cardiovascular health and libido significantly improved. Blood chemistry analyses exhibited broad spectrum safety. A decreasing trend was observed in total cholesterol, triglycerides, and VLDL levels, while an increasing trend was observed in HDL level at 12 weeks of treatment. LDL level decreased significantly at 12-weeks of treatment. No adverse events were observed. CONCLUSION Results demonstrate that Furosap® is safe and effective in improving testosterone levels, cardiovascular health, healthy sperm profile, mental alertness in human male volunteers.

Background and Aim: Capacity for sperm production is affected by age, which is related to the morphology of sperm abnormalities and can affect fertility. The aim of this study was to evaluate the relationship between age and concentrations of testosterone and adiponectin with sperm abnormalities in Simmental bulls. Materials and Methods: The study used 11 bulls, separated into three groups. The first group consisted of five bulls aged 4-5 years, and the second and third groups each consisted of three bulls, aged 6-7 and 8-10 years, respectively. The average sperm motility of the animals ranged from 57.66±2.60% to 70.17±0.22%. Blood samples were obtained from the coccygeal region of the animals. Testosterone and adiponectin analysis was performed using the enzyme-linked immunosorbent assay method. Sperm morphology was evaluated using carbol fuchsin-eosin staining according to the Williams method. Finally, correlations between testosterone and adiponectin concentrations, age, and sperm abnormalities were analyzed using Pearson's correlation analysis. Results: The findings revealed a significant correlation (p

The effect of post-adolescence bisphenol A (BPA) exposure on the reproductive system is not well-defined. We therefore performed this meta-analysis to elucidate the associations between post-adolescence BPA exposure and reproductive-related outcomes. A search was performed on the PubMed, EMBASE, and Web of science databases to identify relevant literature. The standardized mean differences (SMDs) and the 95 % confidence intervals (CIs) were measured by fixed-effects or random-effects models. Publication bias was assessed using funnel plots and Egger's regression test. A total of 40 studies were included in the final analysis. The results showed that post-adolescence BPA exposure was negatively associated with reproductive-related organ weighty (Testis weight: SMD: -0.61; 95 % Cl: -0.85, -0.36; epididymis weight; SMD: -0.43; 95 % Cl: -0.69, -0.17; seminal vesicles weight; SMD: -0.77; 95 % Cl: -1.05, -0.49) and sperm parameters (Sperm motility: SMD: -1.44; 95 % Cl: -1.95, -0.93; epididymal sperm concentration: SMD: -2.26; 95 % Cl: -2.79, -1.72; and abnormal sperm morphology: SMD: 2.41; 95 % Cl: 1.41, 2.86). Moreover, BPA exposure decreased the level of testosterone (T) and superoxide dismutase (SOD), but increased the ratio of serum estradiol (E2) to T. This systematic review demonstrates that post-adolescence exposure to BPA may adversely affect reproductive functions in male rodents.

OBJECTIVE: The study aimed to assess the association between the separate anthropometric indexes including visceral adiposity and metabolic syndrome on male fertility. STUDY DESIGN: In a cross-sectional study, the visceral and subcutaneous fat thickness of 162 participants were measured by ultrasonography. Participants' body mass index, waist circumference, and waist/hip ratio were determined. Participants' biochemical metabolic parameters and reproductive hormones were measured and semen parameters were recorded. Participants were divided into groups according to body mass index and different percentiles of the visceral fat thickness. Differences between groups were investigated by One-way ANOVA, Kruskal-Wallis H, and Pearson Chi-Square test. The relationship between anthropometric measurements and sperm parameters was evaluated by Pearson and Spearman’s rank correlation test. The effect of anthropometric indexes on sperm parameters was evaluated using multivariate regression analysis. RESULTS: It was seen that only total testosterone of sex hormones decreased significantly in the obesity group (p=0.003). There was a significant and reverse association between visceral fat thickness with sperm morphology (rho=–0.2, p=0.01). There was no significant correlation between semen parameters and other anthropometric measurements. In multiple regression analysis, the effect of anthropometric measurements, including visceral fat thickness, on semen parameters was not found, but only smoking was found to be a factor affecting sperm concentration, progressive motility, and morphology (p=0.03, p=0.03, and p=0.01). CONCLUSION: In this study, it was shown that increased obesity was associated with low testosterone levels and increased visceral fat was associated with abnormal sperm morphology. More extensive studies are required on this subject.

Interest in medicinal plants for the management of myriad of conditions including reproductive disorders refractory to orthodox medicinal care is on the increase. Ficus syncomorus and Datura metel are two of such plants with folkloric evidence of aiding fertility in human. This study investigated the effect of aqueous stem-bark extracts (200 mg/kg) of F. syncomorus and D. metel respectively on the sperm characteristics of Yankasa rams. Twelve (12) matured (15 – 16 months) old rams were used in this study and randomly assigned into three (I, II, III) groups of four (4) animals each. Group I served as the control while II and III served as the treatment groups and received daily oral doses (200 mg/kg) of F. syncomorus and D. metel extracts respectively for 7 consecutive days. Semen was collected from all the groups at the end of the treatments using Electro-ejaculation method and evaluated by light microscopy. The mean semen volume (68.70+4.2 to 65.62+2.00) and percentage progressive motile cells significantly (p

Objective: To determine the effect of sperm morphology from the specific sample used for intrauterine insemination (IUI) on clinical pregnancy rates (CPR). Design: Prospective cohort study. Setting: Academic fertility clinic. Patient(s): Couples undergoing IUI July 2016–January 2017. Intervention(s): Morphology slides were prepared from the semen sample produced for IUI. Main Outcome Measure(s): CPR was measured by detection of cardiac activity. Multiple logistic regression modeling was performed to determine the association of sperm morphology with CPR, controlling for age, antimüllerian hormone level, and post-wash total motile sperm count. Result(s): Semen analyses, including Kruger strict criteria for morphology from the actual sample inseminated, were reviewed for 155 couples, comprising 234 total treatment cycles. The percent normal morphology significantly differed between the preliminary semen analysis and the IUI sample (−2.0% +3.7% (95% CI −2.55, −1.53). Of the total 234 treatment cycles, 8.6% resulted in clinical pregnancy. When categorized by strict morphology >4%, 4%

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

Telfairia occidentalis (Hook F.) and Vernonia amygdalina are two commonly consumed vegetables, individually and as recipes, for their nutritive and medicinal values in Africa. Data on reproductive toxicity and DNA damage of the combination of these plants on the male reproductive system is scarce. We evaluated the toxic and genotoxic effects of aqueous extracts of T. occidentalis and V. amygdalina and their combination on the reproductive cells of male Swiss albino mice. Groups of mice exposed to five concentrations (62.5–1000 mg/kg) of each extract or combination as against distilled water and cyclophosphamide (20 mg/kg bwt) as negative and positive control respectively were examined for abnormal sperm morphology, organo-somatic index and pathological changes. Each of the extracts significantly reduced the frequency of aberrant sperm cells, while their combination provoked increasing sperm abnormalities when compared with the negative control. None of the extracts induced adverse effect on body and testes weight of exposed mice. There was no visible histological lesion induced by extracts of V. amygdalina but there were residual bodies indicative of increased spermatogenesis. The extracts of T. occidentalis induced necrosis only at 1000 mg/kg, while with the combination, there were necrotic cells, mild congestion of blood vessels, and the seminiferous tubules had irregular outlines. These indicates that aqueous extracts of T. occidentalis and V. amygdalina individually at the tested doses did not evoke significant induction of genetic damage in the sperm head, and pathological changes unlike the combination in mice.

BACKGROUND: Croton caudatus Geiseler (CCG), a local herb that empirically has been used as traditional medicine for malaria, fever, convulsions, and rheumatic arthritis. This study aimed to investigate the effect of CCG on reproductive and biochemical parameters in male Wistar rats. METHODS: Twenty-four Wistar male rats were divided randomly into four groups, which were treated with CCG aqueous root extract at the concentration of 0-16 mg/kg, via oral gavage. After 21 days of treatment, blood, sperm, and testes were harvested for analyses. Sperm parameters were evaluated using computer-assisted sperm analyser (Hamilton Thorne Sperm Analyzer), and morphometric analyses of histological changes were performed. RESULTS: CCG extract at 8 and 16 mg/kg significantly (p

BACKGROUNDThe precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis—the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility.OBJECTIVE AND RATIONALEThis review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility.SEARCH METHODSRelevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review—protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis.OUTCOMESSpermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility.WIDER IMPLICATIONSA greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.

Exposure to lead (Pb) is a major risk factor in reproductive toxicity, somatic, and germ cell genotoxicity. Exposure via deteriorating Pb paints and contaminated air, soil, and water had been the primary routes. However, with increasing reports of Pb accumulation in mushrooms and other food items may increase the etiology of Pb poisoning. The study herein investigated somatic genotoxicity and reproductive abnormalities in mice fed extracts of Pb-contaminated Pleurotus ostreatus. Male mice were fed aqueous extracts of P. ostreatus cultivated in 0, 10, 20, 100, 200, 500, and 1000 mg/L of Pb-contaminated rice straw for 35 days. Testes were analyzed for Pb accumulation, histopathology and relative weight gain, caudal epididymis for abnormal sperm morphology, and bone marrow for micronucleus test. Concentration-related significant increase in Pb accumulation was observed in P. ostreatus and testes of exposed mice. Decrease testicular weight, congestion of blood vessels, necrosis, and disorganization of the seminiferous tubules were observed in treated mice. In addition, fold increase of 2.78, 3.39, 6.67, 7.21, 9.63, and 9.70 in abnormal sperm morphology in accordance with the Pb concentrations respectively, confirmed reproductive toxicity. Significant increase in micronucleated polychromatic (PCE) and normochromatic (NCE) erythrocytes and concentration-related decrease PCE-NCE ratio in the bone marrow of treated mice suggest genome instability. Pb-contaminated P. ostreatus increased somatic and germ cell genotoxicity in mice. This may predispose the mice to genetic related syndromes and reproductive syndromes. It further suggests caution in the consumption of metal laden wild mushrooms and crop plants.

Background Male infertility is usually caused via the inability to produce adequate quantities of healthy and active sperms. Nicotine (NIC) is an alkaloid organic compound, predominantly found in the leaves of the tobacco plant. The major part of the nicotine is not ionized, so it can easily pass through cell membranes. Meanwhile, most of the disorders are caused by oxidative stress due to oxygen free radicals and other reactive species. Antioxidant supplements and antioxidant-rich foods can reduce induced oxidative stress without becoming destabilized themselves. This study aimed to examine spermato-protective potential of silymarin (SIL), on sperm and in vitro fertility (IVF) rate in nicotine-treated mice. Results Our results show a significant increase in the number of abnormal sperm morphology after nicotine exposure, when compared to control groups (p < 0.05). On the other hand, SIL had a significant effect on the sperm count at each of the treated doses. Further, in the mice that received nicotine plus silymarin, the viable sperm percentage and the progressive sperm motility were significant (p < 0.05). Also, a significant reduction in the number of two-cell embryos and blastocyst-derived embryo was seen with increment in the number of dead embryos in mice receiving nicotine alone (p < 0.05). Conclusions In conclusion, SIL could support prevention of the adverse reproductive effects of nicotine. Moreover, SIL200 mg/kg may be therefore considered as a spermato-protective agent in dietary and herbal supplements.

Background: A mild increase in testicular and epididymal temperatures in men, bulls and rams (pendulous scrotum) inhibits spermatogenesis and increases the percentage of sperm with an abnormal morphology. However, the stages of spermatogenesis that are most sensitive to a mild increase in testicular temperature in men are unknown. The aim of the present study was to explore the effects of a mild induced increase in testicular and epididymal temperature (i.e., testicular temperature maintained below the core body temperature) on sperm morphology in humans depending on the physiological time of spermatogenesis and epididymal transit. Methods: Five healthy volunteers were enrolled in an experimental study in which testicular and epididymal temperatures were increased by maintaining the testes in a supra-scrotal position with a specially designed underwear worn 15±1 h a day for 120 consecutive days. Semen collection was scheduled on specific days depending on spermatogenic stages and epididymal transit. Results: Sperm morphology and the multiple anomalies index (MAI) were analysed before, during and after heating. This mild induced increase in testicular and epididymal temperatures resulted in a significant rise in the percentage of morphologically abnormal spermatozoa on day 34 of heating, which remained elevated throughout the heating period and persisted until 45 days after cessation of heating. The MAI was significantly increased on day 20 throughout the heating period and persisted 45 days after cessation of heating. An increase in the percentage of anomalies in the sperm head, acrosome or tail occurred on days 34 and/or 45 of heating. Abnormal sperm morphology and MAI reverted to control values 73 days after cessation of heating. Conclusions: A mild sustained increase in testicular and epididymal temperature in man leads morphological abnormalities in spermatozoa mainly due to an impairment of spermiogenesis and meiosis.

Research question Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? Design A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1–2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. Results The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 × 106/ml, with only a single participant (1.3%) with a sperm count of 12.5 × 106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. Conclusions The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

Varicocele is one of the most important causes of infertility in men which gradually leads to testicular dysfunction. Testicular heat stress-induced oxidative stress is considered the main cause of pathology in these individuals. In this study, the effects of curcumin and nano-curcumin, as natural antioxidants, were investigated on spermatogenesis and sperm function in varicocele-induced rats. Seventy Wistar rats were randomly divided into seven groups; sham, control, varicocele, varicocele + curcumin 50 mg, varicocele + curcumin 100 mg, varicocele + nano-curcumin 4 mg and varicocele + nano-curcumin 8 mg. After 2 months of antioxidant therapy, all the rats were sacrificed. The results demonstrated that the mean sperm concentration and motility were significantly lower while the mean of abnormal morphology, lipid peroxidation, intracytoplasmic ROS and DNA damage was significantly higher in varicocelised rats compared to control and sham groups (p < .05). Both doses of curcumin and also nano-curcumin were significantly effective in improving the aforementioned parameters except for abnormal sperm morphology, and motility where nano-curcumin (4 mg) was significantly more effective than other groups (p < .05). The results of the current study suggest the application of nano-curcumin is more preferable to curcumin in infertile individuals with varicocele.

Objective: Infertility has become a major health problem worldwide, approximately 10%–15% of male infertility cases can be attributed to genetic mutations. However, the genetic factors contributing to male infertility remain largely unknown. This study aimed to identify genetic mutations associated with morphological abnormalities in sperm.Methods: In this study, we assessed the semen parameters of 60 patients with sperm morphological abnormalities by semen analysis, and subsequently performed targeted next-generation sequencing (NGS) to identify gene mutations. Results: Of the 60 cases of male infertility, 8 individuals (13%) were identified as carrying genetic mutations. In brief, patient 1 carried two heterozygous mutations of SUN5, including c.1066C>T and c.638delC; Patient 2 and Patient 3 had a 109.73 kb homozygous deletion on chromosome 12 in DPY19L2; patient 4 presented two heterozygous mutations (c.1670_1671delinsTT and c.255_258del) of DPY19L2; patient 5 carried a homozygous variant c.1159+1G>A of CCDC40; patient 6 had a heterozygous mutation c.38_43del in the SEPT12 gene; patient 7 had two heterozygous mutations in DNAH1 (c.10060_10061insATCT and c.12278T>C), and patient 8 presented two heterozygous mutations of CFAP43 (c.3658C>T and c.823del). Conclusions: We identified gene mutations associated with sperm morphological abnormalities in a series of male infertility cases. Eight of sixty individuals were identified as carrying gene mutations. Genetic mutations of SUN5, DPY19L2, CCDC40, SEPT12, DNAH1, and CFAP43 might be responsible for male infertility. Our study expanded the landscape of gene mutations related to sperm morphological abnormalities, which might provide new insights into the genetics underlying male infertility.

Cadmium (Cd) as a heavy metal damages testis and decreases fertility, however, antioxidants can improve sperm parameters and decrease male infertility. In this study we investigated the effect of astaxanthin (AST) on sperm parameters, expression levels of CatSper1 and CatSper2 genes in presence of Cd in mice. Thirty adults’ mice were divided into 4 groups, sham group received olive oil and saline (olive oil is the solvent of AST and saline is the solvent of Cd), Cd group received 1 mg/kg Cdcl2, a group received 10 mg/kg AST and 1 mg/kg Cdcl2 and a group received 10 mg/kg AST. The treatments were done intraperitoneally for 14 days. After 14 days sperm parameters were analyzed. Malondialdehyde level, catalase enzyme activity, the alteration of CatSper1 and CatSper2 genes expression were measured in testis. Results showed that Sperm count, viability, CatSper1 gene expression and catalase activity significantly decreased by Cd compared to sham group. Cd significantly increased sperm DNA fragmentation (SDF), abnormal sperm morphology and malondialdehyd level compared to sham group. AST significantly increased sperm count, viability and CatSper1 gene expression and decreased SDF and abnormal sperm in comparison with Cd group. AST protected testis and decreased oxidative stress induced by Cd. Our findings indicated that AST could protect sperm DNA, enhanced CatSper1 gene expression and sperm quality in presence of Cd. No significant differences were found in CatSper2 expression among treatments. Therefore, AST as a strong antioxidant can help to protect the potential of fertility against Cd toxicity.

Infertility is one of the important problems in the modern world. Male infertility is characterized by several clinical manifestations, including low sperm production (oligozoospermia), reduced sperm motility (asthenozoospermia), and abnormal sperm morphology (teratozoospermia). WDR4, known as Wuho, controls fertility in Drosophila. However, it is unclear whether WDR4 is associated with clinical manifestations of male fertility in human. Here, we attempted to determine the physiological functions of WDR4 gene. Two cohorts were applied to address this question. The first cohort was the general population from Taiwan Biobank. Genomic profiles from 68,948 individuals and 87 common physiological traits were applied for phenome-wide association studies (PheWAS). The second cohort comprised patients with male infertility from Wan Fang Hospital, Taipei Medical University. In total, 81 male participants were recruited for the genetic association study. Clinical records including gender, age, total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total sperm number, sperm motility, and sperm morphology were collected. In the first cohort, results from PheWAS exhibited no associations between WDR4 genetic variants and 87 common physiological traits. In the second cohort, a total of four tagging single-nucleotide polymorphisms (tSNPs) from WDR4 gene (rs2298666, rs465663, rs2248490, and rs3746939) were selected for genotyping. We found that SNP rs465663 solely associated with asthenozoospermia. Functional annotations through the GTEx portal revealed the correlation between TT or TC genotype and low expression of WDR4. Furthermore, we used mouse embryonic fibroblasts cells from mwdr4 heterozygous (+/‒) mice for functional validation by western blotting. Indeed, low expression of WDR4 contributed to ROS-induced DNA fragmentation. In conclusion, our results suggest a critical role of WDR4 gene variant as well as protein expression in asthenozoospermia.

MUSASHI (MSI) family plays the main role in the spermatogenesis process. The purpose of this study was the assessment of sperm MSI1 and MSI2, and sperm functional tests in infertile men (n = 30) with varicocele and fertile men (n = 30). Furthermore, MSI1 and MSI2 proteins were assessed in testicular tissue of azoospermic men (n = 9) as well as epididymal spermatozoa and testis of mice. Expression of MSI1 and MSI2 was assessed at RNA and protein levels in human spermatozoa. Sperm concentration and motility were significantly lower, while abnormal sperm morphology, lipid peroxidation, DNA fragmentation and protamine deficiency were significantly higher in men with varicocele compared to fertile individuals. Any significant difference was not observed in the expression of MSI1 and MSI2 mRNA between the two groups. Unlike MSI1 protein that was not detectable in humans, the relative expression of MSI2 protein was similar in varicocele and fertile individuals. The expression level of both Msi1 and Msi2 proteins was also observable in mouse spermatozoa. No significant relationship was observed between sperm functional parameters with expression of these genes. The data of this study demonstrated that although MSI1 and MSI2 play important roles during spermatogenesis, their relative expression in spermatozoa was not affected by varicocele.

Quetiapine is one of the most commonly prescribed antipsychotics to treat schizophrenia in adults, in particular. In this study, quetiapine's effects were assessed on healthy sperm production in rats at repeated-pharmacological doses. Additionally, the effects of quetiapine on oxidative status and hormonal balance were also evaluated in rats. Quetiapine was administered to rats orally at 10, 20, and 40 mg/kg body weight doses for 28 days. At the end of this period, body and organ weights were measured, sperm concentration, motility, and morphology were determined, sperm damage was assessed, and histopathological analysis of testicular tissue was performed. Additionally, serum FSH, LH, and testosterone levels as male reproductive hormones were measured. Catalase, superoxide dismutase, glutathione, and malondialdehyde levels were determined for evaluating the oxidative status of testicular tissue. The findings obtained in this study showed that relative epididymis weights and sperm concentration decreased and abnormal sperm morphology increased in quetiapine-administered rats. Irregularity of typical architecture of the seminiferous tubules and germinal cell disorganization was observed in testicular sections of 20 and 40 mg/kg quetiapine-administered rats. Further, serum LH and testosterone levels decreased in 20 and 40 mg/kg quetiapine-administered rats. Additionally, decreased catalase and superoxide dismutase activities in testicular tissue of quetiapine-administered rats and increased malondialdehyde levels in testicular tissue of 40 mg/kg quetiapine-administered rats were measured. In conclusion, quetiapine treatment decreased sperm quality, altered hormone levels, and induced oxidative stress may be considered potential contributors to this adverse effect.

This study aimed to investigate the effects of heavy metals on measures of male fertility. One hundred and two infertile men with occupational exposure and thirty fertile men were included in this study. Blood and urinary levels of lead, cadmium, zinc and copper were measured by atomic absorption spectrophotometry. Semen parameters and a motile sperm organelle morphology examination were also performed. Measures of hormonal levels, oxidation-reduction potential, DNA fragmentation index and chromatin condensation were assessed for all participants. Heavy metals levels, oxidative stress and DNA quality were significantly higher in the infertile group compared to controls. FSH and testosterone levels were lower in the infertile group. A urinary cadmium level was positively associated with abnormal sperm morphology (r = .225, p < .05). Normal morphology was inversely correlated with the duration of the exposure (r = -.227, p = .022). The blood lead level was positively related to the level of testosterone (r = .223, p = .031). Cadmium and lead blood levels were positively correlated with the level of chromatin decondensation (r = .528, p < .001; r = .280, p = .017). Our study showed that occupational exposure to heavy metals is very harmful to reproductive health. DNA quality and oxidative stress investigations must be recommended for reprotoxic exposed patients prior to in vitro fertilisation treatment.

Background: Acute kidney injury (AKI) is characterized by rapid deterioration of renal functions causing many distant organ injuries. Testicular dysfunction was reported upon chronic renal failure, yet little is known about the underlying mechanism of the damaging effect of AKI on testicular structure and function. Sesame oil was proved to have antioxidant effects.Aim of the work: to assess the effects of AKI on the rat testis and the possible protective role of sesame oil.Material and Methods: Twenty-four adult male albino rats were allocated into 4 groups; control, sesame oil-treated (0.5ml/kg orally for 1week), AKI-induced (10mL/kg of 50% glycerol), and AKI-pretreated with sesame oil. Serum testosterone was assayed. Sperms were analyzed. Biochemical assay of tissue malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were performed. Testes specimens were processed for histological staining and immunohistochemical detection of Bcl2, Ki67, and Androgen receptor (AR). Results: AKI group showed a significant decline in serum testosterone, tissue GSH, and SOD with a significant rise in tissue MDA. Sperms revealed a significant rise in abnormal sperm morphology percentage with a significant decline in sperm count. Histological examination depicted various nuclear and cytoplasmic alterations in the testicular histoarchitecture with a significant rise in the collagen fiber deposition. A significant decline in Bcl2, Ki67, and AR immunohistochemical expression were recorded. Sesame oil pretreatment significantly ameliorated all studied parameters.Conclusions: AKI significantly impacted the testicular structure and function through different mechanisms. Sesame oil efficiently ameliorated this adverse effect through its antioxidant, antiapoptotic, antiproliferative, anti-inflammatory, and antifibrotic activities.

Sperm fibrous sheath, a unique cytoskeletal structure, is implicated in various sperm physiological functions, such as sperm maturation, motility and capacitation. AKAP4 has been described to be required for structural and functional integrity of the fibrous sheath. We generated Akap4-knockout mice line using CRISPR-Cas9 system. Cytomorphology and motility of sperm and testes were studied, confirming loss of Akap4 led to abnormal sperm morphology, motility and infertility. The proteomic components of testes were studied and Akap4 was found to be significantly decreased in the Akap4-knockout mice. Testis single-cell RNA sequencing and analysis revealed three genes with significant change in the general cell population, i.e., Akap4, Haspin, and Ccdc38. The single-cell RNA expression profiles also showed that the major difference between Akap4-knockout and wild-type testes existed in the elongating cell cluster, where in the Akap4-knockout testes, a subgroup of elongating cells with marker genes involved in cell adhesion and migration were increased, while a subgroup of elongating cells marked by mitochondrial sheath genes were decreased. Our results revealed the complex and well-coordinated procedures of spermatogenesis, and substantiated Akap4's indispensable roles in the integrity of sperm flagellum and the step-wise maturation of spermatozoa.

The goal of the study was to evaluate the impact of antiretroviral therapy (ART) on the semen characteristics in HIV-infected men.Materials and methods. A prospective case-control study enrolled 66 HIV-infected male patients who presented for fertility assessment. Group 1 included 51 male patients treated with ART; Group 2 included 15 males who were not receiving ART. 97 and 25 semen samples were analyzed, respectively. HIV status was assessed based on the data regarding the stage and phase of the disease, viral load, CD3+, CD4+, CD8+ counts and the ART duration.Study results. At enrollment in the study, the duration of HIV infection in Group 1 was longer than that in Group 2 (the difference being statistically significant): 5 years (2–9 years) versus 2,5 years (0,4–4,5), respectively (р=0,0004). Median duration of treatment in Group 1 was 1,5 years. The most common type of abnormal semen morphology in ART-treated patients was teratozoospermia (40%), and the percentage of abnormally shaped spermatozoa in this group was higher compared to Group 2 (the difference being statistically significant): 97 (96–98) versus 96 (94,5–96,5); р=0,006). Group 1 demonstrated a negative relationship between the count of abnormally shaped spermatozoa and CD4+ cell count (r=–0,362; р=0,026), disease duration (r=0,173; р=0,173) and sperm count (r=–0,242; р=0,020), progressively motile (category B) sperm count (r=–0,241; р=0,024). The ART duration showed an inverse correlation with the progressively motile sperm count (category B) (r=–0,224; р=0,036). Group 2 demonstrated a statistically significant positive relationship between the CD4+ cell count, the semen volume (r=0,778; p=0,014), and the count of progressively motile (category B) spermatozoa (r=0,667; р=0,05). We also revealed a statistically significant inverse relationship between the viral load and the semen volume (r=–0,669; р=0,035). Sperm DNA fragmentation was found to be higher in HIV-infected patients treated with ART compared to HIV-infected men not receiving ART (15,8% (12,4–23,0) and 14% (10,9–20,5); р=0,533), respectively. Thus, HIV-infected patients treated with ART demonstrated abnormal sperm morphology (increased abnormal sperm count), decreased sperm motility and increased sperm DNA fragmentation level. The percentage of abnormally shaped sperm was higher in patients with lower CD4+ cell counts. In patients with a long history of HIV infection, the sperm count decreases and the count of immotile spermatozoa increases. HIV-infected individuals who are not receiving ART and have high viral loads show decreased semen volume. This value increases upon an increase in the CD4+ cell count.

Background Evidences from human and animal studies suggest that reproductive function may be affected by mercury. The aim of this review was to explore the mercury influence on human fertility. Methods A systematic search was made in PubMED for papers published between 1975–2017, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Increased mercury levels were associated with infertility or subfertility status. Further, infertile subjects with unexplained infertility showed higher levels of mercury in hair, blood and urine than fertile ones. Mercury exposure induced sperm DNA damage and abnormal sperm morphology and motility. Additionally, mercury levels were related with higher incidence of menstrual and hormonal disorders and increased rates of adverse reproductive outcomes. Conclusions Our review showed that mercury negatively impacts human reproduction, affecting the reproductive and endocrine systems in both male and female. However, the molecular mechanisms underlying the mercury-associated decline on fertility remains unknown.

Background: Consumption of alcohol is a major modifiable, rather avoidable lifestyle choice and has shown to affect male fertility. Alcohol has shown to cause various deleterious effects on the male reproductive system. Aims: To compare the effects of alcohol on the sperm count, motility, viability and morphology in alcoholic and non-alcoholic groups. This was a cross sectional study with sample size of 51. There were 25 semen samples of alcoholics (cases) and 26 semen samples of non-alcoholics (controls). Materials and Methods: Adequate history regarding the alcohol consumption was taken and the cases (n=25) were categorized into mild (n=17), moderate (n=8) and severe (n=0) alcoholics as per standard criteria of the CAGE Questionnaire. Semen was examined microscopically and the results were statistically analyzed using ANOVA. Results: Mean sperm count in the non-alcoholics was 58.81 million/ml. It was reduced to 45.44 million/ml and 35.62million/ml in mild and moderate alcoholic groups respectively. (P=0.03). Actively motile sperms in non-alcoholics, mild and moderate alcoholics were found to be 58.08%, 44.41% and 30.62% respectively. (P=0.016). The percentage of sluggishly motile sperms in non-alcoholics, mild and moderate alcoholics were found to be 19.09%, 32.35% and 32.5% respectively. The effect on the percentage of immotile sperms was ambiguous. 15 out of the 26 cases of non-alcoholics showed abnormalities in the morphology. The incidence of abnormal morphology of sperm was higher in the alcoholics. All 25 cases showed abnormal sperm morphology. Alcohol causes a decrease in the sperm vitality. As the grade of alcohol increased, the lowest vitality was in the range of 20-29% and the highest being in the range of 70-79%. Conclusion: The findings reveal that alcohol consumption had significant detrimental effects on the count, morphology and vitality of spermatozoa. It is important to create awareness among people of the adverse effects of alcohol on human health and fertility.

Despite the association between tobacco use and the harmful effects on general health as well as male fertility parameters, smoking remains globally prevalent. The main content of tobacco smoke is nicotine and its metabolite cotinine. These compounds can pass the blood-testis barrier, which subsequently causes harm of diverse degree to the germ cells. Although controversial, smoking has been shown to cause not only a decrease in sperm motility, sperm concentration, and an increase in abnormal sperm morphology, but also genetic and epigenetic aberrations in spermatozoa. Both animal and human studies have highlighted the occurrence of sperm DNA-strand breaks (fragmentation), genome instability, genetic mutations, and the presence of aneuploids in the germline of animals and men exposed to tobacco smoke. The question to be asked at this point is, if smoking has the potential to cause all these genetic aberrations, what is the extent of damage? Hence, this review aimed to provide evidence that smoking has a mutagenic effect on sperm and how this subsequently affects male fertility. Additionally, the role of tobacco smoke as an aneugen will be explored. We furthermore aim to incorporate the epidemiological aspects of the aforementioned and provide a holistic approach to the topic.

International audience; Varicocele is characterized by testicular dysfunction that originates from hyperthermia and hypoxia, leading to defects in testicular tissue and altered spermatozoa structure and function. The varicocele testis is characterized by the presence of intracellular iron deposits that contribute to the associated oxidative stress. Therefore, we tested the hypothesis that administration of an iron-chelating agent, such as deferasirox (DFX), could potentially mitigate the consequences of varicocele on testicular tissue and spermatozoa. Using a well-established rat model of varicocele (VCL), we show that treatment with DFX partially improved the structure and function of the testis and spermatozoa. In particular, sperm motility was markedly restored whereas abnormal sperm morphology was only partially improved. No significant improvement in sperm count was observed that could be associated with the proapoptotic response observed following iron chelation treatment. No reduction in oxidative damage to spermatozoa was observed since lipid peroxidation and DNA integrity were not modified. This was suggested to be a result of increased oxidative stress. Finally, we also saw no indication of attenuation of the endoplasmic reticulum/unfolded protein (ER/UPR) stress response that we recently found associated with the VCL testis in rats.

Introduction: About 50% of infertility is attributed to male factor. Semen analysis is the cornerstone ofthe diagnosis, and treatment of male infertility. The quality of semen varies from country to country. Thepresent study was undertaken to evaluate semen abnormality of infertile Iraqi men as compared to othercountries and to determine whether these parameters are correlated to each other.Patients and Method: The seminal fluid profile was classified according to the WHO manual (2010).Briefly, asthenozoospermia (i.e. progressive motility of spermatozoa below 32%), oligozoospermia(i.e. spermatozoa concentration below 15x106 per ml), teratozoospermia (i.e. morphologically normalspermatozoa below 4%), asthenoteratozoospermia, oligoasthenozoospermia, oligoasthenoteratozoospermia,oligoteratozoospermia, and azoospermia (absence of spermatozoa in the ejaculate)Results: The most striking abnormality is the high percentage of patients withabnormally lowmorphology score (72.09%). The majority of cases have isolated abnormality (teratozoospermia;48.84%). Asthenoteratozoospermia (ATZ) was found in 10.47% and oligoasthenozoospermia (OAZ) andoligoteratozoospermia (OTZ) in 8.14% of cases. The least common pattern was necroteratozoospermia(NTZ) and oligonecroteratozoospermia (ONTZ) 1% each. Azoospermia was encountered in 3.49% of cases.Conclusion: Abnormalsperm morphology is the best indicator of infertility and teratozoosperma is the mostcommon finding in abnormal spermiogram.

Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and ‘9 + 2’ flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.

Male infertility is a global health problem, and the underlying molecular mechanisms are not clearly known. Ion channels and microRNAs (miRNAs), known to function in many vital functions in cells, have been shown to play a significant role in male infertility through changes in their expressions. The study aimed to evaluate the alterations of testicular and/or spermatozoal potassium voltage-gated channel subfamily J member 11 (KCNJ11), Cystic fibrosis transmembrane conductance regulator (CFTR), miR-let-7a and miR-27a expressions in carbamazepine-related male infertility. Here, we showed that carbamazepine reduced sperm motility, increased abnormal sperm morphology, and impaired hormonal balance as well as increased relative testis weight and decreased relative seminal vesicle weight. On the other hand, downregulated KCNJ11 and upregulated miR-let-7a expressions were determined in testis (p < .05). Also, downregulated KCNJ11 and upregulated CFTR and miR-27a expressions were found in spermatozoa (p < .05). Interestingly, altered testicular KCNJ11 and miR-let-7a expressions were correlated with decreased sperm motility and elevated sperm tail defect. Besides, spermatozoal CFTR and miR-27a expressions positively correlated with sperm tail defects. The results indicated a significant relationship between ion channel and/or miRNA expression alterations and impaired sperm parameters due to carbamazepine usage.

Intracytoplasmic sperm injection (ICSI) is increasingly used to treat male-factor infertility when sperm parameters are not proper for intrauterine insemination (IUI) or in vitro fertilization (IVF). Among sperm abnormalities, short tail sperm defect is a rare kind of teratozoospermia, which is a severe cause of male infertility. In this study, we evaluated the ICSI outcomes of infertile men with severely short tail sperm defect. 117 infertile men with primary infertility were included in this study. We evaluated the impact of short tail sperm defect on large ICSI series (228 cycles) outcomes. The fertilisation rate (FR) was 49.0%, the clinical pregnancy rate (PR) was 21.7%, and the delivery rate (DR) was 17.5%. The results of statistical analysis show that there is no relationship between short tail sperm defect and clinical pregnancy. According to the present study, there were patients with successful ICSI outcomes despite the severe defect in their spermatozoa flagella. Our results can be considered in two main aspects: (a) it seems that ICSI could be a proper therapy for infertile men with short-tailed sperm defect and (b) the abnormal sperm morphology (especially in sperm flagellum) is not a reliable predictor for the ICSI outcomes. In conclusion, our study suggests that ICSI should be considered as a proper treatment way for infertile men with severe short tail sperm defect and probably other sperm flagella abnormalities.

Nonobstructive azoospermia (NOA) is an important cause of male infertility, and the genetic pathogenesis is still incompletely understood. The previous study reported that heterozygous mutation of c.346-1G>A in SOHLH1 gene was identified in two NOA patients. However, in our research, this heterozygous mutation was confirmed in a Chinese infertile patient who was suffered from teratozoospermia, and intriguingly, a homozygous mutation of c.346-1G>A in SOHLH1 gene was detected in another patient with severe oligozoospermia. Additionally, we correlated the good prognosis of intracytoplasmic sperm injection (ICSI) in the patient carrying the heterozygous mutation of c.346-1G>A in SOHLH1 gene. Thus, we suggested that the heterozygous mutation of c.346-1G>A in SOHLH1 may not be the direct genetic cause for NOA, and this homozygous mutation might impair spermatogenesis and further lead to the reduced sperm count and abnormal sperm morphology, eventually causing male infertility.

Environmental pollutants such as di-(2-ethylhexyl) phthalate (DEHP) adversely affect reproductive system tissue differentiation and functions with exposure at intrauterine, neonatal or adult stages of life, thereby potentiating male infertility later in life. World health organization estimates a global infertility prevalent rate of 10-15%, and 20-30% among Nigerians, with male factor constituting about 40-50% of infertility cases. This study was designed to investigate the effect(s) of oral vitamins C and E on DEHP induced changes in some semen parameters and serum testosterone concentration in adult Wistar rats. Seventy (70) adult male Wistar rats weighing between 156-250 g were randomised into 7 experimental groups 1, 2, 3, 4, 5, 6 and 7 (group n=10). Animals in groups 1, 2 and 3 were treated with 0.02 mg, 20 mg, 200 mg oral DEHP/kg bw daily respectively, while those in groups 4, 5 and 6, in addition to the above DEHP treatments, were treated with 100 mg ascorbic acid and 67.5 mg α-tocopherol per kg bw daily respectively. Rats in group 7 served as Control and were treated with vehicle. All treatments lasted for 60 days. After, over night fasting, samples of semen and serum were obtained for analysis. Results obtained were expressed as mean ± standard deviation and analyzed for significant differences in means using one way ANOVA and Post Hoc test. Relative to the control reference values, groups exposed to oral DEHP had significant (p

The main purpose of this project is to verify whether there is a difference in the expression of aryl hydrocarbon receptor (AhR) between varicocele (VC) and normal male semen, and determine whether there is a connection with the parameters of semen analysis. The risk factors of infertility in patients with VC were also studied. Semen samples were collected for semen analysis and Western blot. Logistic regression was used to investigate the risk factors associated with infertility in patients with VC. Men with VC had lower AhR expression compared to healthy men; correlation analysis results showed that: AhR expression in patients with VC group was significantly positively correlated with sperm concentration and sperm motility; significantly negatively correlated with the diameter of spermatic veins during Valsalva and the percentage of abnormal sperm morphology; the research results of related risk factors show that the risk of infertility of patients with grade III is 1.67 times that of patients with grades I and II. For each unit of abnormal sperm morphology, the risk of infertility increases 1.04 times. Sperm concentration, total sperm viability and each unit the expression of AhR protein decreases the risk of infertility by 3%, 9% and 11% respectively.

Ethanol consumption is a major cause of male infertility, but the exact mechanism is still largely unknown. This study attempted to investigate the effect of ethanol on sperm morphology, acrosome reaction status and the alteration of the testicular protein expressions. Fourteen male rats were divided into control and ethanol groups (n = 7/each group). Ethanol-treated rats received ethanol (5 g/kg, 40% v/v) via oral gavage for consecutive 14 days. Testosterone hormone, sperm parameters, and testicular and epididymal histopathologies were evaluated. In addition, the expressions of testicular proteins including androgen receptor (AR), heat shock protein 70 (HSP70), steroidogenic acute regulatory protein (StAR) and tyrosine-phosphorylated (TyrPho) proteins were investigated. The results showed that ethanol significantly increased percentage of abnormal sperm morphology and acrosome-reacted spermatozoa. Some seminiferous and ductus epididymal histopathologies were observed in ethanol-treated rats. Significantly, ethanol reduced serum testosterone and expressions of testicular AR and TyrPho proteins. However, the overexpression of StAR and HSP70 proteins in ethanol testis was found. It was concluded that the changes in testicular protein expressions may be involved in mechanism of male infertility caused from ethanol consumption.

Importin α proteins play a central role in the transport of cargo from the cytoplasm to the nucleus. In this study, we observed that male knock-out mice for importin α4, which is encoded by the Kpna4 gene (Kpna4-/- ), were subfertile and yielded smaller litter sizes than those of wild-type (WT) males. In contrast, mice lacking the closely related importin α3 (Kpna3-/- ) were fertile. In vitro fertilization and sperm motility assays demonstrated that sperm from Kpna4-/- mice had significantly reduced quality and motility. In addition, acrosome reaction was also impaired in Kpna4-/- mice. Transmission electron microscopy revealed striking defects, including abnormal head morphology and multiple axoneme structures in the flagella of Kpna4-/- mice. A five-fold increase in the frequency of abnormalities in Kpna4-/- mice compared to WT mice indicates the functional importance of importin α4 in normal sperm development. Moreover, Nesprin-2, which is a component of the linker of nucleus and cytoskeleton complex, was expressed at lower levels in sperm from Kpna4-/- mice and was localized with abnormal axonemes, suggesting incorrect formation of the nuclear membrane-cytoskeleton structure during spermiogenesis. Proteomics analysis of Kpna4-/- testis showed significantly altered expression of proteins related to sperm formation, which provided evidence that genetic loss of importin α4 perturbed chromatin status. Collectively, these findings indicate that importin α4 is critical for establishing normal sperm morphology in mice, providing new insights into male germ cell development by highlighting the requirement of importin α4 for normal fertility.

This study was carried out to evaluate the level of nuclear sperm DNA damage in men with isolated polymorphic teratozoospermia and examining its relationship with apoptosis and oxidative stress. A total of 89 subjects were divided into two groups: men with isolated teratozoospermia (n = 69) and men with normal semen parameters (n = 20) as controls. Sperm DNA breaks were determined by using acridine orange staining. The proportion of viable spermatozoa with mitochondrial transmembrane depolarization was detected by fluorescence microscopy through the use of MitoPTJC-1 staining method. Bivariate Annexin V/6-CFDA analysis was then set out in order to measure the percentage of both viable and dead spermatozoa with phosphatidylserine (PS) externalization. Seminal antioxidant profile (reduced glutathione (GSHr); oxidized glutathione (GSSG); glutathione S-transferase (GST)) and total protein sulfhydryl (P-SH) concentrations were measured spectrophotometrically. Men with isolated teratozoospermia, when compared to controls, showed significantly increased level of single sperm DNA breaks and higher proportions of spermatozoa with phosphatidylserine externalization and mitochondrial depolarization. Among the differently studied oxidative stress seminal parameters, the rates of seminal GSHr, GST, and P-SH were significantly decreased in the teratozoospermic group. However, the seminal rates of GSSG and GST have decreased, but only GST did not show a significant difference. Interestingly, significant correlations were found between the studied apoptotic markers and the rate of atypical sperm forms with the incidences of head abnormalities. Furthermore, positive inter-correlations were found between sperm DNA defects, impaired seminal antioxidant status, and the apoptotic sperm markers. Such data provide clear evidence that the apoptotic alterations are closely correlated to abnormal sperm morphology and DNA damage. Moreover, decreased seminal antioxidant profile may be a crucial factor involved in the mechanism of sperm cell death-mediated DNA breaks in teratozoospermic semen.

Mixture of xenobiotics in Olusosun landfill leachates (OSL) induced somatic and germ cell genotoxicity in eukaryotic cells. However, whether the DNA-damaged germ cells can increase reproductive failure, embryotoxicity and/or teratogenicity during fertilization remained unclear. The study herein investigated reproductive toxicity and embryotoxic effects of OSL in mice using abnormal sperm morphology and dominant lethal mutation assays. Six mice per group were exposed to 0.5 mL of 5, 10, 25, and 50% OSL (v/v, leachate/distilled water) for 5 consecutive days. Similar treatment was giving to distilled water and cyclophosphamide (20 mg/kg body weight), as negative and positive control groups, respectively. At 35 day post-treatment, the mice were sacrificed and examined for cauda epididymal abnormal sperm morphology, testicular weight change and histopathological lesions. Male mice were mated to untreated nulliparous females (1 treated male per 2 untreated females) until vaginal plugs were observed. Pregnant females were sacrificed on 14th day post-mating and uterine content examined for number of implants per female, resorptions, and live and dead fetuses. OSL significantly increased teratozoospermia by 31.02% with amorphous sperm head having the highest frequency and sperm with two heads, the least. Histology of the testes revealed congestion of the interstitial blood vessels, spermatid retention and disorganization of the germinal epithelium from the basal compartment. OSL insignificantly increased absolute and relative testes weights but reduced body weight of exposed mice. There was insignificant induction of dominant lethal mutation, although low fertility was observed in the treated mice. The analyzed physico-chemical parameters and heavy metals/metalloids in OSL were higher than permissible limits. The metals, physico-chemical parameters and other unanalyzed substances in OSL induced abnormal sperm morphology, altered testes pathology, but did not significantly induce dominant lethal mutation in mice. Constituents of OSL are toxic to the male reproductive organs in mice and suggests harmful impact on public health. Indiscriminate disposal of solid wastes in the environment should be prevented.

Prevalence of male infertility in India has reached to approximately 25% of the global infertility problem, making it a great concern for couples as well as clinicians. Among multifactorial aetiology which contributes to male infertility, genetic abnormalities play an important role of risk factor and cannot be ignored. Therefore, recognising and understanding how genetic abnormalities influence male infertility is the foremost agenda of most research groups worldwide. Chromosomal abnormalities, Y chromosome microdeletions, monogenic disorders and genetic variability in several genes (SYCP3, CREM, FHL5, PRM1, NALP14, KLHL10) are the most known and frequent genetic influencers implicated in male infertility studies. Association between genetic, lifestyle and environmental factors and abnormal sperm morphology have been reported previously. Chromosome nondisjunction and/or cytokinesis defects occurring during the first, the second or both meiotic divisions are consistently associated with large-headed spermatozoa. Patients presenting with a monomorphic teratozoospermia such as globozoospermia or macrospermia with more than 85% of the spermatozoa presenting this specific abnormality have been shown to be associated with several key genes for spermatogenesis such as AURKC and DPY19L2. The study of patients with other specific sperm anomalies such as severe alteration of sperm motility, in particular multiple morphological anomalies of the sperm flagella (MMAF) or sperm’s inability to fertilize the oocyte, has also enable the identification of new infertility genes. The identification and study of these genes will shed a much-needed light on the physiopathology of teratozoospermia, and will aid to improve patient management, to provide a basis for the development of therapeutic solutions tailored to the gene defect and to provide the patients with adequate genetic counselling and expected treatment outcome. This chapter emphasises on the association of genetic abnormalities with sperm morphologic defects and their possible implication in understanding and improved management of male infertility.

WOS: 000439441700002, PubMed: 30123865, Background: Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme of the pentose phosphate metabolic pathway that supplies reducing agents by maintaining the level of reduced nicotinamide adenine dinucleotide phosphate. Objective: It was aimed to determine the activity of erythrocyte and spermatozoa G6PD in the breeding and non-breeding seasons in Merino rams. And also, to find out the relation of these parameters with sperm quality parameters for better understanding the role of this enzyme in male fertility. Materials and Methods: 1.5-2 yr-old healthy, 14 Merino rams were involved. Ejaculate samples were collected using an artificial vagina, in October (the breeding season) and April (the non-breeding season). Blood samples were collected prior to sperm collection. Sperm volume (ml), motility (%), mass activity (1-5), concentration (x10(6)), viability (%), abnormal acrosome morphology (%) and abnormal sperm morphology (%) was evaluated. The activities of spermatozoa and erythrocyte G6PD were determined and the relation of sperm parameters with G6PD activity was evaluated. Results: Erythrocyte G6PD activity was higher (p

DNA fragmentation can be deleterious on spermatozoon morphology but the pathogenesis of teratozoospermia associated with DNA breaks is not fully understood, even if oxidative attacks and defects in chromatin maturation are hypothesized. Therefore, this study is one of the first to clarify on the underlying hypothesizes behind such observations. The objectives of our study were to assess the role of oxidative attacks in DNA damage pathogenesis in ejaculated spermatozoa from patients with isolated teratozoospermia. We aimed to assess the correlation of DNA breaks with morphologically abnormal spermatozoa, as well as ROS level and impairment chromatin condensation. A total of 90 patients were divided into two groups, men with isolated teratozoospermia (n = 60) and men with normal semen parameters (n = 30) as controls. DNA fragmentation was evaluated by TUNEL assay; chromatin immaturity was studied using acridine orange and toluidine blue staining. We evaluated the ability of spermatozoa to produce reactive oxygen species with nitro blue tetrazolium staining. Patient with teratozoospermia when compared to fertile men showed significantly higher rates of semen ROS production, sperm hypocondensated chromatin, denaturated DNA, and fragmented DNA. All these parameters were positively correlated with abnormal sperm morphology. The studied DNA integrity markers were also correlated with ROS production. Fragmented DNA is the main pathway leading to morphology defects in the sperm. In fact, impaired chromatin compaction may induce DNA breaks and free radicals, which can break the DNA backbone indirectly, by reducing protamination and disulphide bond formation, as oxidative attack appears to be the major cause of poor semen morphology.

Purpose: Men with abnormal sperm morphology are often counseled that natural conception and intrauterine insemination are ineffective, and in vitro fertilization is the only option. Our objective was to determine the effect of sperm morphology on the pregnancy success of intrauterine insemination.Materials and Methods: We systematically searched for studies published prior to January 2017 that 1) reported ultrasound verified clinical pregnancies per intrauterine insemination cycle, 2) assessed sperm morphology using the Kruger strict criteria and 3) described morphology at the greater than 4% and 4% or less and/or the 1% or greater and less than 1% thresholds. In all studies mean female age was between 25 and 40 years and mean total motile sperm count was greater than 10 million. Estimates were pooled using random effects meta-analysis.Results: Data were extracted from 20 observational studies involving a total of 41,018 cycles. When comparing men at the greater than 4% and 4% or less thresholds, the rate...

The human sperm nucleus contains cytoplasm. However, the origin and incidence of human sperm intranuclear cytoplasmic retention (INCR) remain unknown. The objectives of this study were to observe the morphological origin of INCR within the seminiferous epithelium and investigate the incidence of INCR in fertile and teratozoospermia men using transmission electron microscopy (TEM). By TEM, INCR initially appeared in elongating round spermatid nuclei and varied in size, number, shape, content, location and distribution within sperm nuclei. The teratozoospermia group (n = 16) demonstrated a higher incidence of INCR than did the fertile group (n = 16) (17.6 ± 5.2% vs. 9.7 ± 3.4%; p = 0.000). In the fertile group, no correlations were found between the incidence of INCR and abnormal sperm morphology, nuclear vacuole, acrosome integrity, motility or concentration (p > 0.05). However, the incidence of INCR exhibited a positive relationship with sperm abnormal morphology in the teratozoospermia group (r = 0.616, p = 0.011). These results demonstrate that INCR occurs in the early process of spermatogenesis and is an alteration found in the nucleus. Spermatozoa from teratozoospermia men contained more INCRs than those from fertile males. More attention should be paid to the possibility of spermatozoa containing INCR when using spermatozoa with abnormal head morphology for clinical or diagnostic purposes.

Teratozoospermia is a disorder associated with high abnormal sperm morphology which affects fertility in males. In recent years, it has been described that biomarker-based sperm quality evaluation can alleviate male infertility treatment. Phospholipase C zeta (PLCζ) is a sperm-specific factor which appears to be a predicting biomarker for fertilization potential of males. Following fertilization, PLCζ enters into oocyte cytoplasm and induces oocyte activation, a fundamental stage in initiation of embryo development. Currently, PLCζ parameters, including localization patterns, the proportion of PLCζ-expressing sperm and the expression level, are not defined in polymorphic teratozoospermic men. This study aimed to evaluate PLCζ parameters in polymorphic teratozoospermic men, and compare these parameters with fertile normozoospermic men. Semen samples from thirteen normozoospermic fertile men and twenty-three polymorphic teratozoospermic men were included in this study and evaluated using western blotting and immunofluorescence analyses. Our data indicated significantly lower expression of PLCζ in polymorphic teratozoospermic men, as compared with control men; however, there was no significant difference in localization patterns and the proportion of PLCζ-expressing sperm between polymorphic teratozoospermic patients and control men. Collectively, findings from the present study demonstrated that polymorphic teratozoospermic men did not show abnormal localization patterns or the absence of PLCζ, as compared to the control men; nonetheless, lower expression of PLCζ, considering its role in oocyte activation, might be one of the possible causes of infertility in these patients.