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Journal of Assisted Reproduction and... Mar 2012Male 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.... (Review)
Review
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.
Topics: Animals; Asthenozoospermia; Embryonic Development; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Gene-Environment Interaction; Humans; Infertility, Male; Male; Oligospermia; Protamines; Reproductive Techniques, Assisted; Spermatogenesis; Spermatozoa; Testicular Neoplasms
PubMed: 22290605
DOI: 10.1007/s10815-012-9715-0 -
Frontiers in Physiology 2022Sleep has been related to a variety of health outcomes. However, no association between sleep and asthenozoospermia has been reported. The aim of this study is to first...
Sleep has been related to a variety of health outcomes. However, no association between sleep and asthenozoospermia has been reported. The aim of this study is to first investigate the relationship between sleep status and asthenozoospermia risk. A case-control study, including 540 asthenozoospermia cases and 579 controls, was performed from June 2020 to December 2020 in the infertility clinic from Shengjing Hospital of China Medical University. Data on sleep status were collected by Pittsburgh sleep quality index questionnaires and asthenozoospermia was diagnosed based on the World Health Organization guidelines. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated by logistic regression analysis to assess the aforementioned association. Results of this study demonstrated that compared with total sleep duration of 8-9 h/day, < 8 h/day was related to asthenozoospermia risk (OR: 1.44, 95% CI: 1.05-1.99); compared to good sleep quality, poor sleep quality was associated with asthenozoospermia risk (OR: 1.35; 95% CI: 1.04-1.77). There were multiplicative model interaction effects between sleep quality and tea drinking ( = 0.04), rotating night shift work ( < 0.01) on asthenozoospermia risk. However, we failed to detect any associations between night sleep duration, daytime napping duration, night bedtime, wake-up time, sleep pattern and asthenozoospermia risk. In conclusion, short total sleep duration and poor sleep quality might be related to asthenozoospermia risk. Further well-designed prospective studies are warranted to confirm our findings.
PubMed: 36277203
DOI: 10.3389/fphys.2022.959009 -
International Journal of Molecular... Oct 2022Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and... (Review)
Review
Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and unprotected sexual intercourse. Male infertility etiology can be related to either congenital or acquired factors. The therapeutical approach to male infertility depends on the underlying causes and includes medical and surgical treatments. In recent studies, the potential role of nerve growth factor (NGF) in male reproductive physiology has been proposed. It has been hypothesized that neurotrophins might be involved in testis morphogenesis and regulation of several aspects of spermatogenesis. Moreover, it has been shown that NGF exerts its role on gonadotropin-releasing hormone (GnRH) neurons through the activation of the PKC/p-ERK1/2/p-CREB cascade, which leads to the activation of hypothalamic cells and the consequent activation of hypothalamus-pituitary-gonadal axis (HPG) with the secretion of GnRH. Lastly, it has been shown that the physiology of mature sperm is affected by both exogenous and endogenous NGF. The NGF impact on the HPG axis and its effect on GnRH neurons might be exploited in the therapy of male hypogonadism or used as a protective strategy against gonadal dysfunction related to chemotherapeutic agents. Moreover, the improving effect of NGF on sperm motility and vitality could be useful to enhance assisted reproduction outcomes. NGF could be supplemented to cryopreserved sperm samples to counteract the oxidative stress induced by the frozen and thawing processes. Indeed, the potential clinical applications of NGF in male infertility treatment have been discussed.
Topics: Humans; Pregnancy; Female; Male; Nerve Growth Factor; Sperm Motility; Semen; Gonadotropin-Releasing Hormone; Infertility, Male; Genitalia, Male
PubMed: 36361912
DOI: 10.3390/ijms232113127 -
Cellular and Molecular Life Sciences :... May 2023The sperm flagellum is a specialized type of motile cilium composed of a typical "9 + 2" axonemal structure with peri-axonemal structures, such as outer dense fibers...
The sperm flagellum is a specialized type of motile cilium composed of a typical "9 + 2" axonemal structure with peri-axonemal structures, such as outer dense fibers (ODFs). This flagellar arrangement is crucial for sperm movement and fertilization. However, the association of axonemal integrity with ODFs remains poorly understood. Here, we demonstrate that mouse BBOF1 could interact with both MNS1, an axonemal component, and ODF2, an ODF protein, and is required for sperm flagellar axoneme maintenance and male fertility. BBOF1 is expressed exclusively in male germ cells from the pachytene stage onwards and is detected in sperm axoneme fraction. Spermatozoa derived from Bbof1-knockout mice exhibit a normal morphology, however, reduced motility due to the absence of certain microtubule doublets, resulting in the failure to fertilize mature oocytes. Furthermore, BBOF1 is found to interact with ODF2 and MNS1 and is also required for their stability. Our findings in mice suggest that Bbof1 could also be essential for human sperm motility and male fertility, thus is a novel potential candidate gene for asthenozoospermia diagnosis.
Topics: Animals; Male; Mice; Axoneme; Fertility; Heat-Shock Proteins; Infertility, Male; Mice, Knockout; Semen; Sperm Motility; Spermatozoa
PubMed: 37198331
DOI: 10.1007/s00018-023-04800-0 -
Journal of Clinical Medicine Jan 2020The role of nutraceuticals in the treatment of male infertility, especially in the "idiopathic form", remains the subject of significant debate. Many antioxidants... (Review)
Review
INTRODUCTION
The role of nutraceuticals in the treatment of male infertility, especially in the "idiopathic form", remains the subject of significant debate. Many antioxidants improve sperm motility but the exact mechanism by which they act is still unclear. Although several studies have shown a correlation between sperm motility and mitochondrial function, the effects of antioxidant therapy on mitochondrial membrane potential (MMP) are poorly studied. The first aim of this review was to evaluate the efficacy of antioxidants on mitochondrial function and, consequently, on sperm motility in male infertile patients.
MATERIAL AND METHODS
we performed a systematic search of all randomized controlled and uncontrolled studies available in the literature that reported sperm motility and MMP at baseline and after antioxidant administration in-vivo and in-vitro in patients with idiopathic asthenozoospermia. Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases were used.
RESULTS
Unexpectedly, among 353 articles retrieved, only one study met our inclusion criteria and showed a significant effect of myoinositol on both MMP and sperm motility. We then summarized the main knowledge on anatomy and metabolism of sperm mitochondria, techniques allowing to assess sperm mitochondria function and its relationships with low sperm motility. Finally, we paid special attention to the effect of antioxidant/prokinetic molecules for the treatment of asthenozoospermia.
CONCLUSIONS
This is the first systematic review that has attempted to evaluate the effects of antioxidants on MMP and sperm motility. Although results are not conclusive due to the dearth of studies, the close relationship between mitochondria and sperm motility is clear. The investigation of this correlation could provide valuable information to be exploited in clinical practice for the treatment of male infertility.
PubMed: 32013061
DOI: 10.3390/jcm9020363 -
Cell Death & Disease Feb 2023The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy...
DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath.
The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy chain proteins. They hydrolyze ATP to promote ciliary and flagellar movement. Till now, a variety of dynein protein deficiencies have been linked with asthenospermia (ASZ), highlighting the significance of these structures in human sperm motility. Herein, we detected bi-allelic DNALI1 mutations [c.663_666del (p.Glu221fs)], in an ASZ patient, which resulted in the complete loss of the DNALI1 in the patient's sperm. We identified loss of sperm DNAH1 and DNAH7 rather than DNAH10 in both DNALI1 patient and Dnali1 mice, demonstrating that mammalian DNALI1 is a LIC protein of a partial IDA subspecies. More importantly, we revealed that DNALI1 loss contributed to asymmetries in the most fibrous sheath (FS) of the sperm flagellum in both species. Immunoprecipitation revealed that DNALI1 might interact with the cytoplasmic dynein complex proteins in the testes. Furthermore, DNALI1 loss severely disrupted the transport and assembly of the FS proteins, especially AKAP3 and AKAP4, during flagellogenesis. Hence, DNALI1 may possess a non-classical molecular function, whereby it regulates the cytoplasmic dynein complex that assembles the flagella. We conclude that a DNALI deficiency-induced IDAs injury and an asymmetric FS-driven tail rigid structure alteration may simultaneously cause flagellum immotility. Finally, intracytoplasmic sperm injection (ICSI) can effectively resolve patient infertility. Collectively, we demonstrate that DNALI1 is a newly causative gene for AZS in both humans and mice, which possesses multiple crucial roles in modulating flagellar assembly and motility.
Topics: Animals; Humans; Male; Mice; A Kinase Anchor Proteins; Asthenozoospermia; Axonemal Dyneins; Cytoplasmic Dyneins; Dyneins; Infertility, Male; Mammals; Mutation; Proteins; Semen; Sperm Motility; Sperm Tail
PubMed: 36792588
DOI: 10.1038/s41419-023-05653-y -
Asian Journal of Andrology 2022Large numbers of microbes can be present in seminal fluid, and there are differences in the semen microbiota between normal and abnormal semen samples. To evaluate the...
Large numbers of microbes can be present in seminal fluid, and there are differences in the semen microbiota between normal and abnormal semen samples. To evaluate the semen microbiota in patients with leukocytospermia, 87 seminal fluid samples, including 33 samples with a normal seminal leukocyte count and 54 samples with leukocytospermia, were obtained for a cross-sectional analysis. Twenty samples with a normal seminal leukocyte count had normal sperm parameters (Control group), and 13 samples with a normal seminal leukocyte count were from asthenozoospermia patients (Ast group). However, 32 samples with leukocytospermia were from asthenozoospermia patients (LA group), and only 22 samples with leukocytospermia had normal sperm parameters (Leu group). The 16S ribosomal RNA (rRNA) gene sequencing method was used to sequence the microbiota in the seminal fluid, and multiple bioinformatics methods were utilized to analyze the data. Finally, the results showed that the worse sperm parameters were observed in the leukocytospermia-related groups. Semen microbiota analysis found that there was increased alpha diversity in the leukocytospermia-related groups. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the primary phyla in the seminal fluid. Two microbiota profiles, namely, Lactobacillus-enriched and Streptococcus-enriched groups, were identified in this study. The majority of the samples in the groups with a normal seminal leukocyte count could be categorized as Lactobacillus-enriched, whereas the majority of the leukocytospermia samples could be categorized as Streptococcus-enriched. Our study indicated that males with leukocytospermia have worse sperm parameters and a different semen microbiota composition compared to males with a normal seminal leukocyte count.
Topics: Asthenozoospermia; Cross-Sectional Studies; Humans; Infertility, Male; Male; Microbiota; Semen; Spermatozoa
PubMed: 34916474
DOI: 10.4103/aja202172 -
Andrology Nov 2015Phosholipase A2 (PLA2 ) activity in the seminal plasma and in sperm heads is closely related to sperm motility and male fertility. Therefore, the purpose of this study...
Phosholipase A2 (PLA2 ) activity in the seminal plasma and in sperm heads is closely related to sperm motility and male fertility. Therefore, the purpose of this study was to investigate the possible involvement of different isoforms of phospholipase in asthenozoospermia. To accomplish this, cPLA2 , phospho-cPLA2 , iPLA2 , and sPLA2 were evaluated by immunofluorescence and immunoblot analyses in spermatozoa obtained from 22 normozoospermic men and 28 asthenozoospermic patients. We found significant differences in cPLA2 and its phosphorylated/activated form, iPLA2 , and sPLA2 content and distribution in normal and asthenozoospermic patients. cPLA2 was localized in heads, midpieces, and tails of all spermatozoa as constitutive enzyme, less expressed in the tail of spermatozoa with low progressive motility. While active phospho-cPLA2 distribution was homogeneous throughout the cell body of control-donor spermatozoa, lower levels were detected in the tails of asthenozoospermic patients, as opposed to its strong presence in heads. Low immunofluorescence signal for iPLA2 was found in astenozoospermic patients, whereas sPLA2 was significantly lower in the heads of asthenozoospermic patients. Spermatozoa with low progressive motility showed differences both in terms of total specific activity and of intracellular distribution. cPLA2 , iPLA2 , and sPLA2 specific activities correlated positively and in a significantly manner with sperm progressive motility both in normozoospermic men and asthenozoospermic patients. In conclusion, PLA2 s are expressed in different areas of human spermatozoa. Spermatozoa with low motility showed differences in total specific activity and enzyme distributions. We speculated that PLA2 expression and/or different distribution could be potential biomarkers of asthenozoospermia, one of the major causes of male factor infertility.
Topics: Asthenozoospermia; Biomarkers; Blotting, Western; Case-Control Studies; Cell Membrane; Fertility; Fluorescent Antibody Technique; Group VI Phospholipases A2; Humans; Male; Microscopy, Confocal; Phospholipases A2, Secretory; Phosphorylation; Sperm Count; Sperm Motility; Spermatozoa
PubMed: 26446356
DOI: 10.1111/andr.12101 -
The Journal of Experimental Medicine Feb 2020Asthenozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. We recruited three Pakistani infertile brothers, born to...
Asthenozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. We recruited three Pakistani infertile brothers, born to first-cousin parents, displaying idiopathic asthenozoospermia but no ciliary-related symptoms. Whole-exome sequencing identified a missense variant (c.G5408A, p.C1803Y) in DNAH17, a functionally uncharacterized gene, recessively cosegregating with asthenozoospermia in the family. DNAH17, specifically expressed in testes, was localized to sperm flagella, and the mutation did not alter its localization. However, spermatozoa of all three patients showed higher frequencies of microtubule doublet(s) 4-7 missing at principal piece and end piece than in controls. Mice carrying a homozygous mutation (Dnah17M/M) equivalent to that in patients recapitulated the defects in patients' sperm tails. Further examinations revealed that the doublets 4-7 were destabilized largely due to the storage of sperm in epididymis. Altogether, we first report that a homozygous DNAH17 missense variant specifically induces doublets 4-7 destabilization and consequently causes asthenozoospermia, providing a novel marker for genetic counseling and diagnosis of male infertility.
Topics: Adult; Animals; Asthenozoospermia; Axonemal Dyneins; Cell Line, Tumor; Disease Models, Animal; Female; Genotype; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation, Missense; Sperm Tail; Spermatozoa; Testis; Transfection
PubMed: 31658987
DOI: 10.1084/jem.20182365 -
Frontiers in Endocrinology 2023Infertility is a major disease affecting human life and health, among which male factors account for about half. Asthenoteratozoospermia accounts for the majority of...
INTRODUCTION
Infertility is a major disease affecting human life and health, among which male factors account for about half. Asthenoteratozoospermia accounts for the majority of male infertility. High-throughput sequencing techniques have identified numerous variants in genes responsible for asthenoteratozoospermia; however, its etiology still needs to be studied.
METHOD
In this study, we performed whole-exome sequencing on samples from 375 patients with asthenoteratozoospermia and identified two compound heterozygous variants, a primary ciliary dyskinesia (PCD)-associated gene, in two unrelated subjects. H&E staining, SEM were employed to analyze the varies on sperm of patients, further, TEM was employed to determine the ultrastructure defects. And westernblot and immunostaining were chose to evaluate the variation of structural protein. ICSI was applied to assist the mutational patient to achieve offspring.
RESULT
We identified two HYDIN compound heterozygous variants. Patient AY078 had novel compound heterozygous splice variants (c.5969-2A>G, c.6316+1G>A), altering the consensus splice acceptor site of . He was diagnosed with male infertility and PCD, presenting with decreased sperm progressive motility and morphological abnormalities, and bronchial dilatation in the inferior lobe. Compared to the fertile control, HYDIN levels, acrosome and centrosome markers (ACTL7A, ACROSIN, PLCζ1, and Centrin1), and flagella components (TOMM20, SEPT4, SPEF2, SPAG6, and RSPHs) were significantly reduced in -deficient patients. Using intracytoplasmic sperm injection (ICSI), the patient successfully achieved clinical pregnancy. AY079 had deleterious compound heterozygous missense variants, c.9507C>G (p. Asn3169Lys) and c.14081G>A (p. Arg4694His), presenting with infertility; however, semen samples and PCD examination were unavailable.
DISCUSSION
Our findings provide the first evidence that the loss of function causes asthenoteratozoospermia presenting with various defects in the flagella structure and the disassembly of the acrosome and neck. Additionally, ICSI could rescue this failure of insemination caused by immobile and malformed sperm induced by deficiency.
Topics: Female; Humans; Male; Pregnancy; Asthenozoospermia; East Asian People; Infertility, Male; Proteins; Semen; Spermatozoa
PubMed: 36742411
DOI: 10.3389/fendo.2023.1118841