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Frontiers in Endocrinology 2022Growing evidence has indicated that epigenetic factors might be associated with the pathophysiology of idiopathic nonobstructive azoospermia (iNOA). As the most common...
BACKGROUND
Growing evidence has indicated that epigenetic factors might be associated with the pathophysiology of idiopathic nonobstructive azoospermia (iNOA). As the most common RNA modification, N6-methyladenosine (mA) methylation has recently attracted more attention in the regulation of spermatogenesis; however, its role in the mechanisms of iNOA is still unclear.
OBJECTIVE
To determine the differential expression of mRNA and mA methylation status in the testes of iNOA patients.
METHODS
Testes tissues from diagnosed iNOA and controlled obstructive azoospermia (OA) patients were collected and grouped according to the histological examinations. Total RNA was isolated and quantified by an mA RNA Methylation Quantification Kit. The expression level of mRNAs was detected by qRT-PCR analysis. Differentially expressed mA genes were analyzed using the human ArrayStar mA epitranscriptomic microarray, and bioinformatics analyses were applied.
RESULTS
A total of 36 iNOA and 8 controlled patients were included. The global expression of mA in the iNOA group was significantly decreased. A dosage relationship was observed between the mA decline and the degree of impaired spermatogenesis, with the successive process of normal spermatogeneis, hypospermatogenesis (HP), maturation arrest (MA), and Sertoli cell-only syndrome (SO). Four down-expressed genes () displayed significantly lower expression of mA methylation. Additionally, they also showed a gradually down-expressed tendency in the three groups (OA, HP, SO/MA groups). Moreover, mA reader EIF3A was approved to have differential expression through microarrays analysis, which was consistent with the result from the qRT-PCR test.
CONCLUSIONS
The mA expression was gradually downregulated in the testes tissue from iNOA patients in accordance with the degree of spermatogenic dysfunction. The determined differential expression of mRNA and mA methylation status may represent potentially novel molecular targets for the mechanism study of iNOA in the epigenetic level, which could benefit the understanding of the pathophysiology of iNOA.
Topics: Male; Humans; Testis; Azoospermia; Oligospermia; RNA, Messenger; RNA
PubMed: 36589848
DOI: 10.3389/fendo.2022.1063929 -
Frontiers in Endocrinology 2022Reproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method,...
OBJECTIVE
Reproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied.
METHODS
A bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor's analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time.
RESULTS
The b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E, s-P, ΔFSH, ΔLH, ΔP and ΔE were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients' results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest.
CONCLUSION
Seminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia.
CLINICAL TRIAL REGISTRATION
http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463.
Topics: Male; Humans; Testosterone; Azoospermia; Retrospective Studies; Cohort Studies; Prospective Studies; Follicle Stimulating Hormone; Spermatogenesis; Oligospermia
PubMed: 36568123
DOI: 10.3389/fendo.2022.992556 -
Metabolites Dec 2022Male infertility has increased in the last decade. Pathophysiologic mechanisms behind extreme oligospermia (EO) are not yet fully understood. In new “omics”...
Male infertility has increased in the last decade. Pathophysiologic mechanisms behind extreme oligospermia (EO) are not yet fully understood. In new “omics” approaches, metabolomic can offer new information and help elucidate these mechanisms. We performed a metabolomics study of the seminal fluid (SF) in order to understand the mechanisms implicated in EO. We realized a targeted quantitative analysis using high performance liquid chromatography and mass spectrometry to compare the SF metabolomic profile of 19 men with EO with that of 22 men with a history of vasectomy (V) and 20 men with normal semen parameters (C). A total of 114 metabolites were identified. We obtained a multivariate OPLS-DA model discriminating the three groups. Signatures show significantly higher levels of amino acids and polyamines in C group. The sum of polyunsaturated fatty acids and free carnitine progressively decrease between the three groups (C > EO > V) and sphingomyelins are significantly lower in V group. Our signature characterizing EO includes metabolites already linked to infertility in previous studies. The similarities between the signatures of the EO and V groups are clear evidence of epididymal dysfunction in the case of testicular damage. This study shows the complexity of the metabolomic dysfunction occurring in the SF of EO men and underlines the importance of metabolomics in understanding male infertility.
PubMed: 36557304
DOI: 10.3390/metabo12121266 -
Journal of Assisted Reproduction and... Jan 2023Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time.
METHODS
We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis.
RESULTS
Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10-40 mg/kg). Testicular weight (weighted mean difference [WMD]: - 0.04, 95% CI: - 0.05, - 0.03), testicular index (WMD: - 2.10, 95% CI: - 2.43, - 1.76), and Johnsen score (WMD: - 4.67, 95% CI: - 5.99, - 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 10/ml (WMD: - 32.8, 95% CI: - 44.34, - 21.28), and sperm motility decreased by 37% (WMD: - 0.37, 95% CI: - 0.47, - 0.27). Sperm counts decreased slightly (WMD: - 3.03, 95% CI: - 3.42, - 2.64) in an intratesticular injection of low-dose busulfan (4 - 6 mg/kg), and the model almost returned to normal after one seminiferous cycle.
CONCLUSION
The model using low-dose busulfan (10 - 20 mg/kg) returned to normal after 10 - 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.
Topics: Humans; Mice; Male; Animals; Oligospermia; Busulfan; Asthenozoospermia; Sperm Count; Sperm Motility; Semen
PubMed: 36508035
DOI: 10.1007/s10815-022-02674-y -
Journal of Assisted Reproduction and... Jan 2023The study aims to investigate first the presence of Syncytin 2 and its receptor, MFSD2, in human sperm, and second whether the expressions of Syncytin 1, Syncytin 2, and...
PURPOSE
The study aims to investigate first the presence of Syncytin 2 and its receptor, MFSD2, in human sperm, and second whether the expressions of Syncytin 1, Syncytin 2, and their receptors, SLC1A5 and MFSD2, differ between normozoospermic, asthenozoospermic, oligozoospermic, and oligoasthenozoospermic human sperm samples.
METHODS
The localization patterns and expression levels of syncytins and their receptors were evaluated in normozoospermic (concentration = 88.9 ± 5.5 × 10, motility = 79.2 ± 3.15%, n = 30), asthenozoospermic (concentration = 51.7 ± 7.18 × 10, motility = 24.0 ± 3.12%, n = 15), mild oligozoospermic (concentration = 13.5 ± 2.17 × 10, motility = 72.1 ± 6.5%, n = 15), moderate oligozoospermic (concentration = 8.4 ± 3.21 × 10, motility = 65.1 ± 8.9%, n = 15), severe oligozoospermic (concentration = 2.1 ± 1.01 × 10, motility = 67.5 ± 3.2%, n = 15), and oligoasthenozoospermic (concentration = 5.5 ± 3.21 × 10, motility = 18.5 ± 1.2%, n = 15) samples by immunofluorescence staining and western blot.
RESULTS
Syncytins and their receptors visualized by immunofluorescence showed similar staining patterns with slight staining of the tail in all spermatozoa regardless of normozoospermia, asthenozoospermia, oligozoospermia, or oligoasthenozoospermia. The localization patterns were categorized as equatorial segment, midpiece region, acrosome, and post-acrosomal areas. The combined staining patterns were also detected as acrosomal cap plus post acrosomal region, the midpiece plus equatorial segment, and midpiece plus acrosomal region. However, some sperm cells were categorized as non-stained. Both syncytin proteins were most intensely localized in the midpiece region, while their receptors were predominantly present in the midpiece plus acrosomal region. Conspicuously, syncytins and their receptors showed decreased expression in asthenozospermic, oligozoospermic, and oligoasthenozoospermic samples compared to normozoospermic samples.
CONCLUSION
The expression patterns of HERV-derived syncytins and their receptors were identical regardless of the spermatozoa in men with normozoospermia versus impaired semen quality. Further, asthenozoospermia, oligozoospermia, and oligoasthenozoospermia as male fertility issues are associated with decreased expression of both syncytins and their receptors.
Topics: Humans; Male; Semen Analysis; Asthenozoospermia; Oligospermia; Semen; Endogenous Retroviruses; Spermatozoa; Sperm Motility; Minor Histocompatibility Antigens; Amino Acid Transport System ASC
PubMed: 36469256
DOI: 10.1007/s10815-022-02673-z -
EMBO Reports Feb 2023Following meiotic recombination, each pair of homologous chromosomes acquires at least one crossover, which ensures accurate chromosome segregation and allows reciprocal...
Following meiotic recombination, each pair of homologous chromosomes acquires at least one crossover, which ensures accurate chromosome segregation and allows reciprocal exchange of genetic information. Recombination failure often leads to meiotic arrest, impairing fertility, but the molecular basis of recombination remains elusive. Here, we report a homozygous M1AP splicing mutation (c.1074 + 2T > C) in patients with severe oligozoospermia owing to meiotic metaphase I arrest. The mutation abolishes M1AP foci on the chromosome axes, resulting in decreased recombination intermediates and crossovers in male mouse models. M1AP interacts with the mammalian ZZS (an acronym for yeast proteins Zip2-Zip4-Spo16) complex components, SHOC1, TEX11, and SPO16. M1AP localizes to chromosomal axes in a SPO16-dependent manner and colocalizes with TEX11. Ablation of M1AP does not alter SHOC1 localization but reduces the recruitment of TEX11 to recombination intermediates. M1AP shows cytoplasmic localization in fetal oocytes and is dispensable for fertility and crossover formation in female mice. Our study provides the first evidence that M1AP acts as a copartner of the ZZS complex to promote crossover formation and meiotic progression in males.
Topics: Animals; Female; Male; Mice; Meiosis; Microtubule-Associated Proteins; DNA-Binding Proteins; Cell Cycle Proteins; Multiprotein Complexes
PubMed: 36440627
DOI: 10.15252/embr.202255778 -
Andrology Mar 2023Due to the heterogeneous distribution of seminiferous tubules (STs) in patients with nonobstructive azoospermia (NOA), retrieving enough good quality spermatozoa for...
A complete dissection of the whole testicular parenchyma is required in most patients with nonobstructive azoospermia to obtain enough good quality testicular spermatozoa for ICSI.
BACKGROUND
Due to the heterogeneous distribution of seminiferous tubules (STs) in patients with nonobstructive azoospermia (NOA), retrieving enough good quality spermatozoa for ICSI may require a complete testicular dissection. According to the only available study in this field, spermatozoa may be found in the testis surface in 34.2% of patients, while a deeper testicular dissection is able to provide spermatozoa for ICSI in 28% of those without spermatozoa in the testis surface.
OBJECTIVES
To determine the probability of finding enough spermatozoa for ICSI at the initial wide incision of the testis in a cohort of men with NOA undergoing microdissection testicular spermatozoa extraction (mTESE).
MATERIALS AND METHODS
We evaluated 276 patients, aged 37 (20-62) years, who underwent unilateral (86, 31.15%) or bilateral (190, 68.8%) mTESE from January 2018 through December 2021. During mTESE, the entire surface of the testicular parenchyma was explored first in search for dilated STs: if no/ not enough spermatozoa were retrieved, the deeper portion of the parenchyma was explored.
RESULTS
Spermatozoa were retrieved in 137 patients (49.6%). Histopathology demonstrated Sertoli-cell only syndrome in 65.6% of operated testes, while maturation arrest was found in 19.5%, hypospermatogenesis (HS) in 12.7%, and hyalinosis in 2%. Spermatozoa were obtained from the testis surface in 46 of 276 patients (16.6%), and after a complete dissection in 91 subjects (32.9%). On multivariate logistic regression, only the histopathological subcategory HS was predictive of the chance of retrieving spermatozoa from the surface of the testis (OR 3.24, 95% CI 1.37-7.69, p = 0.007).
DISCUSSION
Most patients with NOA, particularly those with unfavorable histopathological patterns, require a complete dissection of the testicular parenchyma to obtain enough good quality for ICSI.
CONCLUSIONS
By enabling the complete exploration of the testicular parenchyma, mTESE is to be preferred to cTESE to retrieve spermatozoa in patients with NOA.
Topics: Male; Humans; Testis; Azoospermia; Sperm Injections, Intracytoplasmic; Retrospective Studies; Sperm Retrieval; Spermatozoa; Oligospermia
PubMed: 36416145
DOI: 10.1111/andr.13344 -
Cureus Oct 2022Human immunodeficiency virus (HIV) is a virus that affects the immune system and attacks immune cells called CD4 while also raising the risk and severity of other...
A Successful Pregnancy Outcome in a Human Immunodeficiency Virus Serodiscordant Couple in a Single Cycle of In Vitro Fertilization/Intracytoplasmic Sperm Injection: A Case Report.
Human immunodeficiency virus (HIV) is a virus that affects the immune system and attacks immune cells called CD4 while also raising the risk and severity of other infections and diseases. Despite the fact that HIV can infect persons of any age, the majority of infected people are those of reproductive age between 15 and 44 years. Many women and men with HIV desire children. Plenty of HIV-positive adults worldwide wish to have a child. As a result, reproductive desires have emerged as clinically significant in patients with HIV/acquired immunodeficiency syndrome (AIDS). We present a case of a 35-year-old male who is HIV-1 seropositive and his 32-year-old healthy wife who is seronegative who visited an in vitro fertilization (IVF) clinic. The couple was married for four years, facing primary infertility, and had a history of failure of three successive intrauterine insemination (IUI) cycles. The couple abstained from physical contact when the husband was discovered HIV positive. The couple wanted to have their own biological, completely healthy child. The male was undertaking highly active antiretroviral therapy (HAART). On the performance of the semen analysis test, the male was discovered to have oligospermia. The blood test of the female revealed that her anti-Mullerian hormone (AMH) level was raised, and ultrasound indicated polycystic ovarian syndrome (PCOS). The couple was suggested IVF/intracytoplasmic sperm injection (ICSI) treatment due to failure of IUI cycles in the past. Medications were given to the wife for her PCOS. Self-oocytes were retrieved from the wife, and the husband's semen sample was washed with the semen washing method (density gradient (DG) and swim up). By confirming in the sample that HIV is not present, ICSI was done. Three blastocyst stage embryos were transferred on day 6 of progesterone. After 14 days, the test report of the β-human chorionic gonadotropin (hCG) hormone came positive. Around 39 weeks later, she successfully delivered a baby boy who was later tested for HIV, and the report was negative.
PubMed: 36381787
DOI: 10.7759/cureus.29981 -
BMC Urology Nov 2022Despite the generally accepted World Health Organization guidelines on semen analysis, an individual's results can display significant variation when performed across... (Observational Study)
Observational Study
BACKGROUND
Despite the generally accepted World Health Organization guidelines on semen analysis, an individual's results can display significant variation when performed across time or in different laboratories. Semen parameters are in fact highly variable measures that can differ significantly between various analyses. Numerous researchers have discovered a wide range of semen parameters within each individual male, but only a few studies included the analysis of semen parameters variability in patients with infertility. The aim of this study was to evaluate the inter- and intra-individual variability of semen parameters in men of reproductive age with normozoospermia and those with oligozoospermia.
METHODS
Five hundred and thirteen who provided ≥ 2 semen samples (798 samples in total) using an at-home mail-in kit over a period of about 2 years were enrolled in the study. Semen samples collection using Give Legacy at-home mail-in semen collection kit; semen analysis at a CLIA-certified laboratory.
RESULTS
The degree of intra-subject variation across all semen parameters was lower in men with normozoospermia compared to men with oligozoospermia. Men with normozoospermia furthermore demonstrated a level of intra-subject variation that was lower than inter-subject variation across all measured parameters. No association was observed between intra-subject coefficients of variation in any of the semen parameters, including sperm concentration, sperm count, motile sperm count, total motility, progressive motility, the percentage of sperm with normal morphology, and the age, duration of abstinence, and BMI of the men.
CONCLUSION
The results of this observational study confirm the significant variability in semen parameters in men with normozoospermia and oligozoospermia, as measured from at-home semen collection kit samples. This further underscore the importance of securing multiple samples for analysis to provide a robust assessment of male fertility.
Topics: Male; Humans; Semen; Sperm Motility; Oligospermia; Sperm Count; Spermatozoa; Infertility, Male
PubMed: 36380340
DOI: 10.1186/s12894-022-01134-0 -
Journal of Applied Clinical Medical... Jan 2023Total-body irradiation (TBI) has been used as a part of the conditioning regimen for patients undergoing hematopoietic stem cell transplantation for certain nonmalignant...
Total-body irradiation (TBI) has been used as a part of the conditioning regimen for patients undergoing hematopoietic stem cell transplantation for certain nonmalignant conditions such as sickle cell disease. Although effective, TBI can cause lasting side effects for pediatric patients. One of these potential side effects includes oligospermia or even permanent azoospermia. Although many investigators have studied ways to shield the testicles during the TBI for nonmalignant conditions, there is no set standard. We describe the technical aspects of effective techniques to shield the testicles of male pediatric patients undergoing TBI. We verified that our techniques reduced the testicular dose by approximately 80%-85% of the TBI prescription dose in four male pediatric patients, keeping the dose well below the documented doses that can cause permanent infertility and hypogonadism.
Topics: Child; Humans; Male; Testis; Hematopoietic Stem Cell Transplantation
PubMed: 36355034
DOI: 10.1002/acm2.13842