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Andrology Jul 2018Oligo-astheno-teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to... (Review)
Review
BACKGROUND
Oligo-astheno-teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to contribute to its pathogenesis. The aim of this European Academy of Andrology guideline was to provide an overview of these factors and to discuss available management options.
MATERIALS AND METHODS
PubMed was searched for papers in English for articles with search terms: male infertility and oligo-astheno-teratozoospermia. For evidence-based recommendations, the GRADE system was applied. Issues related to urogenital infections/inflammations have not been included in this document as they will be covered by separate guidelines.
RESULTS
For men with oligo-astheno-teratozoospermia, the European Academy of Andrology recommends: A general physical examination to assess signs of hypogonadism. A scrotal physical examination to assess (i) the testes and epididymes for volume and consistency, (ii) deferent ducts for total or partial absence, and (iii) occurrence of varicocoele. Performing two semen analyses, according to World Health Organization guidelines to define an oligo-astheno-teratozoospermia. An endocrine evaluation. A scrotal ultrasound as part of routine investigation. Karyotype analysis and assessment of Yq microdeletions in infertile men with a sperm concentration ≤5 × 10 /mL. Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for incomplete congenital obstruction of the genital tract. Against quitting physical activity to improve the chance of achieving pregnancy. Against androgen replacement therapy to improve the chance of achieving pregnancy. Assisted reproduction techniques to improve the chance of achieving pregnancy, in case other treatment options are not available or not efficient. Androgen replacement therapy in patients with biochemical/clinical signs of hypogonadism, after completion of the fertility treatment.
CONCLUSION
These guidelines can be applied in clinical work and indicate future research needs.
Topics: Humans; Male; Oligospermia
PubMed: 30134082
DOI: 10.1111/andr.12502 -
Journal of Nutritional Science 2023This review discusses epigenetic mechanisms and the relationship of infertility in men and women in relation to parameters pertaining to nutrition. The prevalence of... (Review)
Review
This review discusses epigenetic mechanisms and the relationship of infertility in men and women in relation to parameters pertaining to nutrition. The prevalence of infertility worldwide is 8-12 %, and one out of every eight couples receives medical treatment. Epigenetic mechanisms, aging, environmental factors, dietary energy and nutrients and non-nutrient compounds; more or less energy intake, and methionine come into play in the occurrence of infertility. It also interacts with vitamins B12, D and B6, biotin, choline, selenium, zinc, folic acid, resveratrol, quercetin and similar factors. To understand the molecular mechanisms regulating the expression of genes that affect infertility, the environment, the role of genotype, age, health, nutrition and changes in the individual's epigenotype must first be considered. This will pave the way for the identification of the unknown causes of infertility. Insufficient or excessive intake of energy and certain macro and micronutrients may contribute to the occurrence of infertility as well. In addition, it is reported that 5-10 % of body weight loss, moderate physical activity and nutritional interventions for improvement in insulin sensitivity contribute to the development of fertility. Processes that pertain to epigenetics carry alterations which are inherited yet not encoded via the DNA sequence. Nutrition is believed to have an impact over the epigenetic mechanisms which are effective in the pathogenesis of several diseases like infertility. Epigenetic mechanisms of individuals with infertility are different from healthy individuals. Infertility is associated with epigenetic mechanisms, nutrients, bioactive components and numerous other factors.
Topics: Humans; Male; Female; Infertility, Female; Epigenesis, Genetic; Genotype
PubMed: 37771507
DOI: 10.1017/jns.2023.62 -
Andrology Sep 2017For over 30 years, sperm morphology assessment has been one of the most common tests in evaluation of fertility. This review examines the clinical relevance of sperm... (Review)
Review
For over 30 years, sperm morphology assessment has been one of the most common tests in evaluation of fertility. This review examines the clinical relevance of sperm morphology assessment in the diagnosis of infertility and in assisted reproductive technology, as well as its analytical reliability. Publications on the pathophysiology, the analytical reliability of the test and its clinical relevance in diagnosis and in Assisted Reproductive Technology (ART) were evaluated. This review compared and discussed study methodologies and results, including patient characteristics, preparation, smear staining methods and classification systems. The assessment of the percentage of some abnormalities such as for example thin head, amorphous head, or bent or asymmetrical neck is of little clinical use, and their pathophysiology is not well explained as most are physiological traits. Some studies have highlighted correlations between the percentage of normal forms and functional sperm abnormalities, as well as correlations with ability to conceive in vivo and, in some situations, with the success of intra-uterine insemination (IUI) or conventional IVF. However, except in the case of some specific sperm defects (easy to detect with 99 or 100% of spermatozoa affected) and which are often linked to genetic disorders (globozoospermia, macrocephaly, decapitated sperm syndrome and fibrous sheath dysplasia), sperm morphology assessment has very poor sensitivity and specificity in the diagnosis of infertility. Moreover, there is very little evidence that indices of multiple sperm defects [sperm deformity index (SDI), teratozoospermia index (TZI), and multiple abnormalities index (MAI)] are relevant. Above all, many publications report a major lack of analytical reliability of this test, mainly in assessment of the details of sperm abnormalities. Many questions arise concerning how and when sperm morphology should be assessed, and how to interpret the thresholds of normal forms. Questions are raised on the real clinical impact of this test.
Topics: Humans; Infertility, Male; Male; Reference Values; Reproductive Techniques, Assisted; Semen Analysis; Spermatozoa
PubMed: 28692759
DOI: 10.1111/andr.12389 -
Science Bulletin Oct 2022Teratozoospermia is usually associated with defective spermiogenesis and is a disorder with considerable genetic heterogeneity. Although previous studies have identified...
Teratozoospermia is usually associated with defective spermiogenesis and is a disorder with considerable genetic heterogeneity. Although previous studies have identified several teratozoospermia-associated genes, the etiology remains unknown for a majority of affected men. Here, we identified a homozygous missense mutation and a compound heterozygous mutation of CCIN in patients suffering from teratozoospermia. CCIN encodes the cytoskeletal protein Calicin that is involved in the formation and maintenance of the highly regular organization of the calyx of mammalian spermatozoa, and has been proposed to play a role in sperm head structure remodeling during the process of spermiogenesis. Our morphological and ultrastructural analyses of the spermatozoa obtained from all three men harboring deleterious CCIN mutants reveal severe head malformation. Further immunofluorescence assays unveil markedly reduced levels of Calicin in spermatozoa. These patient phenotypes are successfully recapitulated in mouse models expressing the disease-associated variants, confirming the role of Calicin in male fertility. Notably, all mutant spermatozoa from mice and human patients fail to adhere to the zona mass, which likely is the major mechanistic reason for CCIN-mutant sperm-derived infertility. Finally, the use of intra-cytoplasmic sperm injections (ICSI) successfully makes mutated mice and two couples with CCIN variants have healthy offspring. Taken together, our findings identify the role of Calicin in sperm head shaping and male fertility, providing important guidance for genetic counseling and assisted reproduction treatments.
Topics: Humans; Male; Animals; Mice; Teratozoospermia; Seeds; Spermatozoa; Infertility, Male; Mutation; Mammals
PubMed: 36546111
DOI: 10.1016/j.scib.2022.09.026 -
BMC Medicine Nov 2023The epididymis is crucial for post-testicular sperm development which is termed sperm maturation. During this process, fertilizing ability is acquired through the...
BACKGROUND
The epididymis is crucial for post-testicular sperm development which is termed sperm maturation. During this process, fertilizing ability is acquired through the epididymis-sperm communication via exchange of protein and small non-coding RNAs (sncRNAs). More importantly, epididymal-derived exosomes secreted by the epididymal epithelial cells transfer sncRNAs into maturing sperm. These sncRNAs could mediate intergenerational inheritance which further influences the health of their offspring. Recently, the linkage and mechanism involved in regulating sperm function and sncRNAs during epididymal sperm maturation are increasingly gaining more and more attention.
METHODS
An epididymal-specific ribonuclease T2 (RNase T2) knock-in (KI) mouse model was constructed to investigate its role in developing sperm fertilizing capability. The sperm parameters of RNase T2 KI males were evaluated and the metabolic phenotypes of their offspring were characterized. Pandora sequencing technology profiled and sequenced the sperm sncRNA expression pattern to determine the effect of epididymal RNase T2 on the expression levels of sperm sncRNAs. Furthermore, the expression levels of RNase T2 in the epididymal epithelial cells in response to environmental stress were confirmed both in vitro and in vivo.
RESULTS
Overexpression of RNase T2 caused severe subfertility associated with astheno-teratozoospermia in mice caput epididymis, and furthermore contributed to the acquired metabolic disorders in the offspring, including hyperglycemia, hyperlipidemia, and hyperinsulinemia. Pandora sequencing showed altered profiles of sncRNAs especially rRNA-derived small RNAs (rsRNAs) and tRNA-derived small RNAs (tsRNAs) in RNase T2 KI sperm compared to control sperm. Moreover, environmental stress upregulated RNase T2 in the caput epididymis.
CONCLUSIONS
The importance was demonstrated of epididymal RNase T2 in inducing sperm maturation and intergenerational inheritance. Overexpressed RNase T2 in the caput epididymis leads to astheno-teratozoospermia and metabolic disorder in the offspring.
Topics: Mice; Animals; Male; Epididymis; Semen; Spermatozoa; RNA, Small Untranslated; Metabolic Diseases
PubMed: 37993934
DOI: 10.1186/s12916-023-03158-1 -
Nature Communications Aug 2021The sperm head-to-tail coupling apparatus (HTCA) ensures sperm head-tail integrity while defective HTCA causes acephalic spermatozoa, rendering males infertile. Here, we...
The sperm head-to-tail coupling apparatus (HTCA) ensures sperm head-tail integrity while defective HTCA causes acephalic spermatozoa, rendering males infertile. Here, we show that CENTLEIN is indispensable for HTCA integrity and function, and that inactivation of CENTLEIN in mice leads to sperm decapitation and male sterility. We demonstrate that CENTLEIN directly interacts with both SUN5 and PMFBP1, two proteins localized in the HTCA and related with acephalic spermatozoa syndrome. We find that the absence of Centlein sets SUN5 and PMFBP1 apart, the former close to the sperm head and the latter in the decapitated tail. We show that lack of Sun5 results in CENTLEIN and PMFBP1 left in the decapitated tail, while disruption of Pmfbp1 results in SUN5 and CENTLEIN left on the detached sperm head. These results demonstrate that CENTLEIN cooperating with SUN5 and PMFBP1 participates in the HTCA assembly and integration of sperm head to the tail, indicating that impairments of CENTLEIN might be associated with acephalic spermatozoa syndrome in humans.
Topics: Animals; Cell Cycle Proteins; Cells, Cultured; Cytoskeletal Proteins; HEK293 Cells; Humans; Infertility, Male; Male; Membrane Proteins; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Mutation; Protein Binding; Sperm Head; Sperm Tail; Spermatozoa; Teratozoospermia; Mice
PubMed: 34389728
DOI: 10.1038/s41467-021-25227-w -
Acta Bio-medica : Atenei Parmensis Sep 2019Infertility is a widespread clinical problem affecting 8-12% of couples worldwide. Of these, about 30% are diagnosed with idiopathic infertility since no causative... (Review)
Review
Infertility is a widespread clinical problem affecting 8-12% of couples worldwide. Of these, about 30% are diagnosed with idiopathic infertility since no causative factor is found. Overall 40-50% of cases are due to male reproductive defects. Numerical or structural chromosome abnormalities have long been associated with male infertility. Monogenic mutations have only recently been addressed in the pathogenesis of this condition. Mutations of specific genes involved in meiosis, mitosis or spermiohistogenesis result in spermatogenic failure, leading to the following anomalies: insufficient (oligozoospermia) or no (azoospermia) sperm production, limited progressive and/or total sperm motility (asthenozoospermia), altered sperm morphology (teratozoospermia), or combinations thereof. Androgen insensitivity, causing hormonal and sexual impairment in males with normal karyotype, also affects male fertility. The genetic causes of non-syndromic monogenic of male infertility are summarized in this article and a gene panel is proposed.
Topics: Genetic Predisposition to Disease; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Infertility, Male; Male; Mutation
PubMed: 31577257
DOI: 10.23750/abm.v90i10-S.8762 -
Frontiers in Genetics 2023
PubMed: 37091790
DOI: 10.3389/fgene.2023.1187445 -
EBioMedicine Jul 2023Male infertility is a worldwide population health concern, but its aetiology remains largely understood. Although CFAP70 variants have already been reported in two...
BACKGROUND
Male infertility is a worldwide population health concern, but its aetiology remains largely understood. Although CFAP70 variants have already been reported in two oligo-astheno-teratozoospermia (OAT) individuals by sequencing, animal evidence to support CFAP70 as a credible OAT-pathogenic gene is lacking.
METHOD
Cfap70-KO mice were generated to explore the physiological role of CFAP70. CFAP70 variants were detected in infertile men with OAT by whole exome sequencing and Sanger sequencing confirmation. Cfap70-truncated mice were further generated to explore the pathogenicity of the nonsense variant of CFAP70 identified in the proband.
FINDINGS
Here, we demonstrate that Cfap70-KO mice are sterile mainly due to OAT and further identify a Chinese infertile man carrying a homozygous nonsense variant (c.2962C > T/p.R988X) of CFAP70. Cfap70-truncated mice lacking 5-8 tetratricopeptide repeats (TPRs) mimic the patient's symptoms. CFAP70 is required for the biogenesis of spermatid flagella partially by regulating the expression of OAT-associated proteins (e.g., QRICH2), assisting the cytoplasmic preassembly of the calmodulin- and radial spoke-associated complex (CSC), and controlling the manchette localization of axoneme-related proteins. Moreover, we suggest that CFAP70-associated male infertility could be overcome by intracytoplasmic sperm injection (ICSI) treatment.
INTERPRETATION
Overall, we demonstrate that CFAP70 is necessary to assemble spermatid flagella and that CFAP70 gene could be used as a diagnostic target for male infertility with OAT in the clinic.
FUNDING
This study was supported by the National Key Research and Development Project (2019YFA0802101 to S.C), Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education (to S.C), Central Government to Guide Local Scientific and Technological Development (ZY21195023 to B.W), and Basic Research Projects of Central Scientific Research Institutes (to B.W).
Topics: Humans; Male; Animals; Mice; Semen; Infertility, Male
PubMed: 37352829
DOI: 10.1016/j.ebiom.2023.104675 -
Human Reproduction Open 2023Are dietary phytochemicals associated with the risk of teratozoospermia?
STUDY QUESTION
Are dietary phytochemicals associated with the risk of teratozoospermia?
SUMMARY ANSWER
Dietary intake of carotene, including total carotene, α-carotene, β-carotene as well as retinol equivalent, and lutein + zeaxanthin, were inversely correlated with the risk of teratozoospermia.
WHAT IS KNOWN ALREADY
Phytochemicals are natural plant derived bioactive compounds, which have been reported to be potentially associated with male reproductive health. To date, no study has investigated the association between phytochemical intake and the risk of teratozoospermia.
STUDY DESIGN SIZE DURATION
This hospital-based case-control study, which included 146 newly diagnosed teratozoospermia cases and 581 controls with normozoospermia from infertile couples, was conducted in a hospital-based infertility clinic in China, from June 2020 to December 2020.
PARTICIPANTS/MATERIALS SETTING METHODS
Dietary information was collected using a validated semi-quantitative 110-item food frequency questionnaire. Unconditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between phytochemical (i.e. phytosterol, carotene, flavonoid, isoflavone, anthocyanidin, lutein + zeaxanthin, and resveratrol) intake and the risk of teratozoospermia.
MAIN RESULTS AND THE ROLE OF CHANCE
We observed a decreased risk of teratozoospermia for the highest compared with the lowest tertile consumption of total carotene (OR = 0.40, 95% CI = 0.21-0.77), α-carotene (OR = 0.53, 95% CI = 0.30-0.93), β-carotene (OR = 0.47, 95% CI = 0.25-0.88), retinol equivalent (OR = 0.47, 95% CI = 0.24-0.90), and lutein + zeaxanthin (OR = 0.35, 95% CI = 0.19-0.66), with all of the associations showing evident linear trends (all trend <0.05). In addition, significant dose-response associations were observed between campestanol and α-carotene consumption and the risk of teratozoospermia. Moreover, there was a significant multiplicative interaction between BMI and lutein + zeaxanthin intake ( interaction <0.05).
LIMITATIONS REASONS FOR CAUTION
The cases and controls were not a random sample of the entire target population, which could lead to admission rate bias. Nevertheless, the controls were enrolled from the same infertility clinic, which could reduce the bias caused by selection and increase the comparability. Furthermore, our study only included a Chinese population, therefore caution is required regarding generalization of our findings to other populations.
WIDER IMPLICATIONS OF THE FINDINGS
Dietary phytochemicals, namely carotene, lutein, and zeaxanthin, might exert a positive effect on teratozoospermia. These phytochemicals are common in the daily diet and dietary supplements, and thus may provide a preventive intervention for teratozoospermia.
STUDY FUNDING/COMPETING INTERESTS
This study was funded by Natural Science Foundation of Liaoning Province (No. 2022-MS-219 to X.B.W.), Outstanding Scientific Fund of Shengjing Hospital (No. M1150 to Q.J.W.), Clinical Research Cultivation Project of Shengjing Hospital (No. M0071 to B.C.P.), and JieBangGuaShuai Project of Liaoning Province (No. 2021JH1/1040050 to Y.H.Z.). All authors declared that there was no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
PubMed: 37346245
DOI: 10.1093/hropen/hoad025