scholarly journals Effects of Environmental and Pathological Hypoxia on Male Fertility

Author(s):  
Zhibin Li ◽  
Sumin Wang ◽  
Chunli Gong ◽  
Yiyang Hu ◽  
Jiao Liu ◽  
...  

Male infertility is a widespread health problem affecting approximately 6%–8% of the male population, and hypoxia may be a causative factor. In mammals, two types of hypoxia are known, including environmental and pathological hypoxia. Studies looking at the effects of hypoxia on male infertility have linked both types of hypoxia to poor sperm quality and pregnancy outcomes. Hypoxia damages testicular seminiferous tubule directly, leading to the disorder of seminiferous epithelium and shedding of spermatogenic cells. Hypoxia can also disrupt the balance between oxidative phosphorylation and glycolysis of spermatogenic cells, resulting in impaired self-renewal and differentiation of spermatogonia, and failure of meiosis. In addition, hypoxia disrupts the secretion of reproductive hormones, causing spermatogenic arrest and erectile dysfunction. The possible mechanisms involved in hypoxia on male reproductive toxicity mainly include excessive ROS mediated oxidative stress, HIF-1α mediated germ cell apoptosis and proliferation inhibition, systematic inflammation and epigenetic changes. In this review, we discuss the correlations between hypoxia and male infertility based on epidemiological, clinical and animal studies and enumerate the hypoxic factors causing male infertility in detail. Demonstration of the causal association between hypoxia and male infertility will provide more options for the treatment of male infertility

2005 ◽  
Vol 173 (4S) ◽  
pp. 371-371
Author(s):  
Nikolai Leonhartsberger ◽  
Kadir Tosun ◽  
Germar-Michael Pinggera ◽  
Michael Mitterberger ◽  
Peter Rehder ◽  
...  

Zygote ◽  
2020 ◽  
Vol 28 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Jie Zhang ◽  
De-Ling Kong ◽  
Bin Xiao ◽  
Hong-Jie Yuan ◽  
Qiao-Qiao Kong ◽  
...  

SummaryStudies have indicated that psychological stress impairs human fertility and that various stressors can induce apoptosis of testicular cells. However, the mechanisms by which psychological stress on males reduces semen quality and stressors induce apoptosis in testicular cells are largely unclear. Using a psychological (restraint) stress mouse model, we tested whether male psychological stress triggers apoptosis of spermatozoa and spermatogenic cells through activating tumour necrosis factor (TNF)-α signalling. Wild-type or TNF-α−/− male mice were restrained for 48 h before examination for apoptosis and expression of TNF-α and TNF receptor 1 (TNFR1) in spermatozoa, epididymis, seminiferous tubules and spermatogenic cells. The results showed that male restraint significantly decreased fertilization rate and mitochondrial membrane potential, while increasing levels of malondialdehyde, active caspase-3, TNF-α and TNFR1 in spermatozoa. Male restraint also increased apoptosis and expression of TNF-α and TNFR1 in caudae epididymides, seminiferous tubules and spermatogenic cells. Sperm quality was also significantly impaired when spermatozoa were recovered 35 days after male restraint. The restraint-induced damage to spermatozoa, epididymis and seminiferous tubules was significantly ameliorated in TNF-α−/− mice. Furthermore, incubation with soluble TNF-α significantly reduced sperm motility and fertilizing potential. Taken together, the results demonstrated that male psychological stress induces apoptosis in spermatozoa and spermatogenic cells through activating the TNF-α system and that the stress-induced apoptosis in spermatogenic cells can be translated into impaired quality in future spermatozoa.


1998 ◽  
Vol 26 (4) ◽  
pp. 421-480
Author(s):  
Krys Bottrill

Recent developments in biomarkers relating to the interrelationship of diet, disease and health were surveyed. Most emphasis was placed on biomarkers of deleterious effects, since these are of greatest relevance to the subject of this review. The area of greatest activity was found to be that relating to biomarkers of mutagenic, genotoxic and carcinogenic effects. This is also one of the major areas of concern in considerations of the beneficial and deleterious effects of dietary components, and also the area in which regulatory testing requires studies of the longest duration. A degree of progress has also been made in the identification and development of biomarkers relating to certain classes of target organ toxicity. Biomarkers for other types of toxicity, such as immunotoxicity, neurotoxicity, reproductive toxicity and developmental toxicity, are less developed, and further investigation in these areas is required before a comprehensive biomarker strategy can be established. A criticism that recurs constantly in the biomarker literature is the lack of standardisation in the methods used, and the lack of reference standards for the purposes of validation and quality control. It is encouraging to note the growing acknowledgement of the need for validation of biomarkers and biomarker assays. Some validation studies have already been initiated. This review puts forward proposals for criteria to be used in biomarker validation. More discussion on this subject is required. It is concluded that the use of biomarkers can, in some cases, facilitate the implementation of the Three Rs with respect to the testing of food chemicals and studies on the effects of diet on health. The greatest potential is seen to be in the refinement of animal testing, in which biomarkers could serve as early and sensitive endpoints, in order to reduce the duration of the studies and also reduce the number of animals required. Biomarkers could also contribute to establishing a mechanistic basis for in vitro test systems and to facilitating their validation and acceptance. Finally, the increased information that could result from the incorporation of biomarker determinations into population studies could reduce the need for supplementary animal studies. This review makes a number of recommendations concerning the prioritisation of future activities on dietary biomarkers in relation to the Three Rs. It is emphasised, however, that further discussions will be required among toxicologists, epidemiologists and others researching the relationship between diet and health.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Alireza Hosseini ◽  
Mehrdad Shahrani ◽  
Shirin Asgharian ◽  
Maryam Anjomshoa ◽  
Ayoob Rostamzadeh ◽  
...  

Abstract Background Cyclophosphamide (CP) is an anti-neoplastic alkylating agent that is extensively used in different chemotherapy regimens. Adverse effects on the reproductive system, especially spermatogenesis, are one of the most important side effects of this drug. It is medically essential to use complementary and alternative drugs. Herbal drugs have long been used as a complementary treatment. Our purpose was to study the effect of hydroalcoholic Allium atroviolaceum L. extract on spermatogenesis in CP-treated mice. Results CP affected a significant decrease in sperm count, motility, viability, and morphology. Sperm count was significantly higher in the all extract groups than in the group of control (p<0.001) and CP group (p<0.001, p<0.01). Sperm motility was significantly greater in the extract (100 and 200mg/kg) groups than in the group of control (p<0.05 and <0.001). Sperm immotility and rotational movement were significantly higher in the CP group than in the CP+extract groups (p<0.001). The sperm viability was significantly greater in the CP+extract (200mg/kg) group than in the CP group (p<0.001). The number of headless sperm, sperm with initial tail, with coiled tail, and sperm with curved body, was significantly lower in the CP+extract (200mg/kg) group than in the CP group (p<0.001). Conclusion A. atroviolaceum extract treatment significantly improved CP-induced reproductive toxicity.


2019 ◽  
Vol 31 (8) ◽  
pp. 1386 ◽  
Author(s):  
Fatma Uysal ◽  
Gokhan Akkoyunlu ◽  
Saffet Ozturk

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine–phosphate–guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P&lt;0.05). DNMT3A expression was significantly decreased in the RS arrest, SC arrest and SCO groups compared with the hyposperm group (P&lt;0.05). DNMT3B expression was significantly lower in the RS arrest and SCO groups than in the hyposperm group (P&lt;0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Bolan Yu ◽  
Zhaofeng Huang

Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathioneS-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted.


2006 ◽  
Vol 91 (7) ◽  
pp. 2732-2737 ◽  
Author(s):  
Katharina M. Main ◽  
Jorma Toppari ◽  
Anne-Maarit Suomi ◽  
Marko Kaleva ◽  
Marla Chellakooty ◽  
...  

Abstract Context: Recent studies showed that male reproductive health problems, such as cryptorchidism, hypospadias, testicular cancer, and low sperm quality, are more prevalent in Denmark than in Finland. Objectives: We hypothesized that, if fetal testicular dysgenesis contributed to these observations, differences in gonadal development and the hypothalamus-pituitary-testis axis would already be detectable perinatally. Thus, we investigated healthy newborn boys in both countries. Design: This was a prospective, longitudinal population-based study. Setting: Two primary obstetric centers were included at the University Hospitals of Copenhagen, Denmark, and Turku, Finland. Participants: The participants of the study included 633 Danish and 1044 Finnish boys, born at term with appropriate weight for gestational age. Interventions: Ultrasound determination of testis size at 0, 3, and 18 months and blood sampling (n = 727) at 3 months were analyzed. Main Outcome Measures: Testicular volume and reproductive hormones were measured. Results: Testis volume was significantly higher at all ages in Finnish than in Danish boys (medians, 98 vs. 95, 185 vs. 119, and 188 vs. 136 mm3, respectively; P &lt; 0.00001). Testis growth from birth to 3 months was larger in Finnish than in Danish boys (mean, 75 vs. 26 mm3; P &lt; 0.0001). Serum hormone levels were higher in Finnish than Danish boys for inhibin B (median, 456 vs. 385 pg/ml; P &lt; 0.0001), FSH (1.33 vs. 1.21 IU/liter; P &lt; 0.036), and SHBG (143 vs. 136 nmol/liter; P &lt; 0.022). Inhibin B was significantly positively correlated to testicular volume (r = 0.25; P &lt; 0.006). Conclusions: The larger testes and higher inhibin B levels most likely represent a bigger volume of seminiferous tubules in Finnish compared with Danish boys. Although this phenomenon may be attributable to a genetic difference between the two countries, it may also reflect environmental factors influencing testicular development.


2016 ◽  
Vol 22 (2) ◽  
pp. 223-226 ◽  
Author(s):  
Farnaz Sohrabvand ◽  
Somaye Mahroozade ◽  
Sodabe Bioos ◽  
Seyed Mohammad Nazari ◽  
Fataneh Hashem Dabaghian

Introduction. Idiopathic male infertility is a global problem with almost no definite medicinal treatment. Most patients have to go through intrauterine insemination or assisted reproductive technology for achieving fertility. Unfortunately, success rates are low in cases with very low sperm count. Therefore it seems that improvement in sperm quality can have beneficial effects on assisted reproductive technology outcome. Case Report. A 39-year-old man with history of infertility for 6 years was referred to the traditional medicine clinic with a recurrent unsuccessful intracytoplasmic sperm injection trial. His sperm analysis showed severe oligoasthenoteratozoospermia. After taking a traditional remedy he had a remarkable improvement in his sperm parameters, which led to the formation of 8 embryos in the following intracytoplasmic sperm injection cycle. Conclusion. Traditional medicine presents various food and remedy options for treating male infertility. It seems that combination therapy can be beneficial in obtaining better results in treatment of male idiopathic infertility.


2021 ◽  
Vol 11 ◽  
Author(s):  
Vincenza Precone ◽  
Rossella Cannarella ◽  
Stefano Paolacci ◽  
Gian Maria Busetto ◽  
Tommaso Beccari ◽  
...  

BackgroundInfertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large number of genes that may be involved in male infertility. This study aimed to test idiopathic male infertile patients negative for a validated panel of “diagnostic” genes, for a wide panel of genes that we have defined as “pre-diagnostic.”MethodsWe developed a next-generation sequencing (NGS) gene panel including 65 pre-diagnostic genes that were used in 12 patients who were negative to a diagnostic genetic test for male infertility disorders, including primary spermatogenic failure and central hypogonadism, consisting of 110 genes.ResultsAfter NGS sequencing, variants in pre-diagnostic genes were identified in 10/12 patients who were negative to a diagnostic test for primary spermatogenic failure (n = 9) or central hypogonadism (n = 1) due to mutations of single genes. Two pathogenic variants of DNAH5 and CFTR genes and three uncertain significance variants of DNAI1, DNAH11, and CCDC40 genes were found. Moreover, three variants with high impact were found in AMELY, CATSPER 2, and ADCY10 genes.ConclusionThis study suggests that searching for pre-diagnostic genes may be of relevance to find the cause of infertility in patients with apparently idiopathic primary spermatogenic failure due to mutations of single genes and central hypogonadism.


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