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Journal of Assisted Reproduction and... Jun 2024To investigate the occurrence of idiopathic secondary azoospermia (ISA) in men with oligospermia over time and identify risk factors for ISA in this population.
PURPOSE
To investigate the occurrence of idiopathic secondary azoospermia (ISA) in men with oligospermia over time and identify risk factors for ISA in this population.
METHODS
This was a retrospective cohort study conducted in a university-affiliated male infertility clinic. A total of 1056 oligospermic men (concentration < 15 million/ml (M/ml) and no azoospermia) with at least two SA done between 2000 and 2019 were included. The primary outcome was the occurrence of ISA by oligospermia severity.
RESULTS
In the entire cohort, 31 patients (2.9%) eventually became azoospermic with time. The ≤ 1 M/ml extremely severe oligospermia (ESO) group (283 patients) had significantly higher rates of ISA in each time period compared to the 1-5 M/ml severe oligospermia (SO) (310 patients) and 5-15 M/ml mild oligospermia (MO) (463 patients) groups (p < 0.05 for all comparisons), with rates of 21.1% in the ESO, 4.8% in the SO, and 0% in the MO group (p = 0.02) after 3-5 years, reaching 32% after 5 years in the ESO group compared to no cases in the other two groups (p = 0.006). Parameters shown to predict ISA were initial concentration < 1 M/ml (OR 22.12, p < 0.001) and time interval of > 3 and 5 years (OR 4.83 and 6.84, p = 0.009 and < 0.001, respectively), whereas testosterone levels were negatively associated with ISA (OR 0.88, p = 0.03).
CONCLUSIONS
Men with ≤ 1 M/ml, especially those with low testosterone levels, have a dramatically increased chance of becoming azoospermic with time. Therefore, sperm banking should be recommended in these cases. Men with a sperm concentration above 1 M/ml have low chances of becoming azoospermic, even after 3 or more years.
PubMed: 38941005
DOI: 10.1007/s10815-024-03179-6 -
JCI Insight Jun 2024Spermatogenesis requires precise posttranslational control in the endoplasmic reticulum (ER), but the mechanism remains largely unknown. The protein disulfide isomerase...
Spermatogenesis requires precise posttranslational control in the endoplasmic reticulum (ER), but the mechanism remains largely unknown. The protein disulfide isomerase (PDI) family is a group of thiol oxidoreductases responsible for catalyzing the disulfide bond formation of nascent proteins. In this study, we generated 14 strains of KO mice lacking the PDI family enzymes and found that only PDI deficiency caused spermatogenesis defects. Both inducible whole-body PDI-KO (UBC-Cre/Pdifl/fl) mice and premeiotic PDI-KO (Stra8-Cre/Pdifl/fl) mice experienced a significant decrease in germ cells, testicular atrophy, oligospermia, and complete male infertility. Stra8-Cre/Pdifl/fl spermatocytes had significantly upregulated ER stress-related proteins (GRP78 and XBP1) and apoptosis-related proteins (Cleaved caspase-3 and BAX), together with cell apoptosis. PDI deletion led to delayed DNA double-strand break repair and improper crossover at the pachytene spermatocytes. Quantitative mass spectrometry indicated that PDI deficiency downregulated vital proteins in spermatogenesis such as HSPA4L, SHCBP1L, and DDX4, consistent with the proteins' physical association with PDI in normal testes tissue. Furthermore, PDI served as a thiol oxidase for disulfide bond formation of SHCBP1L. Thus, PDI plays an essential role in protein quality control for spermatogenesis in mice.
Topics: Animals; Male; Spermatogenesis; Protein Disulfide-Isomerases; Mice; Mice, Knockout; Testis; Endoplasmic Reticulum Chaperone BiP; Infertility, Male; Apoptosis; Spermatocytes; Endoplasmic Reticulum Stress; Oligospermia
PubMed: 38912589
DOI: 10.1172/jci.insight.177743 -
BMC Genomics Jun 2024Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation...
BACKGROUND
Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS.
RESULTS
Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups.
CONCLUSIONS
The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.
Topics: Humans; DNA Methylation; Male; Asthenozoospermia; Adult; Oligospermia; Spermatozoa; Spermatogenesis; Case-Control Studies; Epigenesis, Genetic
PubMed: 38886667
DOI: 10.1186/s12864-024-10491-z -
PloS One 2024In this cross-sectional prospective study, advanced next-generation sequencing technology was used to compare the molecular karyotyping of individual human sperm cells...
In this cross-sectional prospective study, advanced next-generation sequencing technology was used to compare the molecular karyotyping of individual human sperm cells in infertile couples with severe oligoteratozoospermia (i.e., low sperm count and motility) to those of infertile couples with normal semen. Fourteen infertile couples who were patients at Ramathibodi Hospital in Bangkok, Thailand, were recruited from January to November 2023, and they were categorized into two groups based on semen analysis results. The study group comprised couples with severe oligoteratozoospermia, whereas the control group exhibited normal semen. Individual sperm cells from the semen samples were isolated by the micromanipulation technique for subsequent whole-genome amplification and next-generation sequencing, where the primary outcome was the aneuploidy rate. Seventy individual sperm cells were isolated with a 90% success rate for amplification. The next-generation sequencing results showed that the aneuploidy rate was 25%-75%, with a mean of 48.28% in the study group. In contrast, the control group exhibited aneuploidy rates of 0-75%, with a mean of 15.15%. The difference between the two groups was statistically significant (odds ratio: 5.8, 95% confidence interval: 1.30-26.03). Sperm cells of the study group showed a threefold higher aneuploidy rate than those in the control group, even though the sperm cells were selected by micromanipulation for their normal morphology. Comprehensive counseling is recommended to address elevated aneuploidy rates that potentially surpass those of the general infertile population. Guidance on preimplantation genetic testing is also recommended to ensure the transfer of embryos with normal chromosomes.
Topics: Humans; Male; Cross-Sectional Studies; Prospective Studies; Adult; Spermatozoa; Oligospermia; Aneuploidy; High-Throughput Nucleotide Sequencing; Semen Analysis; Karyotyping; Infertility, Male; Single-Cell Analysis
PubMed: 38875276
DOI: 10.1371/journal.pone.0303350 -
BMC Urology Jun 2024Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause...
BACKGROUND
Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China.
METHODS
We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E, were quantified using the enzyme-linked immunosorbent assay (ELISA).
RESULTS
The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p < 0.001). In comparison, the deletion rate of the AZFc region was significantly higher in patients with oligozoospermia (3.08% vs. 6.30%, p < 0.001). Additionally, the AZFb + c subregion association deletion was observed in the highest proportion among all patients (0.89%, 8/897), followed by AZFa + b + c deletion (0.56%, 5/897), and exclusively occurred in patients with azoospermia. Hormone analysis revealed FSH (21.63 ± 2.01 U/L vs. 10.15 ± 0.96 U/L, p = 0.001), LH (8.96 ± 0.90 U/L vs. 4.58 ± 0.42 U/L, p < 0.001) and PRL (263.45 ± 21.84 mIU/L vs. 170.76 ± 17.10 mIU/L, p = 0.002) were significantly increased in azoospermia patients with microdeletions. Still, P and E levels were not significantly different between the two groups.
CONCLUSIONS
The incidence of AZF microdeletion can reach 7.13% in infertile men in Hainan province, and the deletion of the AZFc subregion is the highest. Although the Y chromosome microdeletion rate is distinct in different regions or populations, the regions mentioned above of the Y chromosome may serve an indispensable role in regulating spermatogenesis. The analysis of Y chromosome microdeletion plays a crucial role in the clinical assessment and diagnosis of male infertility.
Topics: Humans; Male; Chromosomes, Human, Y; Infertility, Male; Chromosome Deletion; China; Sex Chromosome Aberrations; Adult; Sex Chromosome Disorders of Sex Development; Reproductive Techniques, Assisted; Luteinizing Hormone; Follicle Stimulating Hormone; Azoospermia; Prolactin; Oligospermia; Testosterone; Estradiol; Semen Analysis
PubMed: 38867229
DOI: 10.1186/s12894-024-01503-x -
Forensic Science, Medicine, and... Jun 2024Identifying body fluids can be a critical clue that aids in reconstructing the crime scene. Semen and vaginal fluid identification is crucial, especially in cases of...
Identifying body fluids can be a critical clue that aids in reconstructing the crime scene. Semen and vaginal fluid identification is crucial, especially in cases of sexual assault. The majority of forensic studies focused on identifying normal body fluids and neglected the expression variation of semen in pathology. To differentiate between vaginal fluids, fertile and infertile semen samples (oligospermia and azoospermia) using miR 20b and miR197. A total of 48 body fluid samples, divided as 16 vaginal fluids, 16 fertile semen, and 16 infertile semen samples (8 with oligospermia and 8 with azoospermia), were collected, and the expression levels of miR-20b and miR-197 were detected by the SYBR Green real-time quantitative PCR technique. Our results showed significant different expression of these miRNAs in normal semen compared to vaginal and infertile semen. Moreover, we designed a model based on Fisher's discriminant function to forecast the group affiliations of unidentified samples. With three novel equations, we were able to accurately distinguish between semen and vaginal fluid, fertile and infertile semen, and oligospermia and azoospermia semen samples with validation accuracy of 81.3%, 100%, and 100%, respectively. MiR-20b and miR-197 expression levels are efficient and appropriate markers to distinguish semen from vaginal fluid and to differentiate between fertile and infertile semen samples. However, the present study is a preliminary study based on clinical samples, and the potential role of these markers in differentiating real crime scene samples is still unknown, so we recommend further research to investigate these markers expression while using forensic samples.
PubMed: 38856935
DOI: 10.1007/s12024-024-00831-6 -
Clinical and Experimental Reproductive... Jun 2024To investigate whether long non-coding RNA (lncRNA) Gm8097 (LncGm8097) is associated with male infertility.
OBJECTIVE
To investigate whether long non-coding RNA (lncRNA) Gm8097 (LncGm8097) is associated with male infertility.
METHODS
The expression and bilogical role of LncGm8097 were investigated.
RESULTS
LncGm8097 expression was down-regulated in the testis tissues with moderate and severe hypospermatogenesis compared with those with normal spermatogenesis and mild hypospermatogenesis (p<0.05). LncGm8097 down-regulation significantly promoted apoptosis and inhibited proliferation in GC1 and GC2 cells. In addition, LncGm8097 was significantly down-regulated in mouse model of hypospermatogenesis and correlated with cell apoptosis and proliferation. LncGm8097 was located immediately upstream of PRPS2, and correlated with Bcl-2/P53/caspase 6/caspase 9 signal pathway.
CONCLUSION
LncGm8097 down-regulation correlates with hypospermatogenesis, which may offer new insights into the pathogenesis of male infertility.
PubMed: 38853128
DOI: 10.5653/cerm.2024.06835 -
Alternative Therapies in Health and... Jun 2024To explore the relationship between DAZ (Deleted in Azoospermia, DAZ) and DAZLA (Deleted in Azoospermia-like autosomal) gene deletion and male idiopathic azoospermia and...
AIM
To explore the relationship between DAZ (Deleted in Azoospermia, DAZ) and DAZLA (Deleted in Azoospermia-like autosomal) gene deletion and male idiopathic azoospermia and oligozoospermia.
METHODS
80 patients with azoospermia (azoospermia group) and 80 patients with oligozoospermia (oligozoospermia group) who were treated at our hospital from April 2021 to April 2023, and male volunteers who underwent health examinations at our hospital during the same period were selected as the control group, The incidence of DAZ and DAZLA gene locus deletion in three groups of men was detected by polymerase chain reaction (PCR), and the differences of reproductive hormone levels and main semen parameters among the three groups were compared. The azoospermia were stratified according to whether DAZ and DAZLA gene locus deletion occurred.
RESULTS
DAZ gene locus deletion rate in azoospermia and oligospermia groups was considerably higher than in the control group (P < .05). The DAZLA gene locus deletion rate in the azoospermia group was apparently higher than that in the oligospermia and control groups (P < .05). The semen volume was compared between azoospermia and oligospermia patients and controls (P > .05). Sperm concentration, sperm survival rate, the proportion of normal morphological sperm, and the proportion of progressive motility sperm in the oligospermia group were lower than those in the control group (P < .05). The levels of serum T (Testosterone, T) and T/LH in the azoospermiaspermia group were lower than those in the control group (P < .05). Serum LH (Luteinizing Hormone) and FSH (Follicular Stimulating Hormone) in azoospermia group and oligospermia group were higher than those in the control group (P < .05). The Serum LH determination value of the azoospermia group is higher than the oligospermia group (P < .05). Serum T/LH in the azoospermia group was lower than in the oligospermia group (P < .05). The serum T and T/LH values in azoospermia male patients with DAZ and DAZLA gene deletion were lower than those without deletion (P < .05). Sperm concentration and survival rate of oligospermatism male patients with DAZ gene deletion were lower than those without deletion (P < .05). Sperm and serum T and T/LH values of oligospermatism male patients with DAZ gene deletion were lower than those without deletion (P < .05).
CONCLUSION
The incidence of DAZ and DAZLA gene locus deletion in male patients with idiopathic azoospermia and oligozoospermia was higher than in normal males. The gene locus deletion was related to decreased androgen level, sperm count and motility.
PubMed: 38843424
DOI: No ID Found -
Reproductive Sciences (Thousand Oaks,... Jun 2024The long arm of the Y chromosome (Yq) contains many amplified and palindromic sequences that are prone to self-reorganization during spermatogenesis, and tiny...
The long arm of the Y chromosome (Yq) contains many amplified and palindromic sequences that are prone to self-reorganization during spermatogenesis, and tiny submicroscopic segmental deletions in the proximal Yq are called Y chromosome microdeletions (YCM). A retrospective study was conducted on male infertility patients of Zhuang ethnicity who presented at Reproductive Medical Center of Nanning between January 2015 and May 2023. Seminal fluid was collected for standard examination. YCM were detected by using a combination of multiplex PCR and agarose gel electrophoresis. Preparation of peripheral blood chromosomes and karyotyping of chromosomes was performed. 147 cases (9.22%) of YCM were detected in 1596 male infertility patients of Zhuang ethnicity. Significant difference was found in the detection rate of YCM between the azoospermia group and the oligospermia group (P < 0.001). Of all types of YCM, the highest detection rate was AZFc (n = 83), followed by AZFb + c (n = 28). 264 cases (16.54%) of sex chromosomal aberrations were detected. The most prevalent karyotype was 47, XXY (n = 202). The detection rate of sex chromosomal aberrations in azoospermia group was higher than that in severe oligospermia group and oligospermia group, and the differences were significant (P < 0.001). 28 cases (1.57%) of autosomal aberrations and 105 cases (6.58%) of chromosomal polymorphism were identified. The current research has some limitations due to the lack of normal men as the control group but suggests that YCM and chromosomal aberrations represent key genetic factors influencing spermatogenesis in infertile males of Zhuang ethnicity in Guangxi.
PubMed: 38836967
DOI: 10.1007/s43032-024-01568-x -
International Journal of Surgery Case... Jul 2024Polyorchidism, or supernumerary testis, is a rare urogenital congenital disorder. Because of its rarity, there is no approved standard treatment protocol for preserving...
INTRODUCTION AND IMPORTANCE
Polyorchidism, or supernumerary testis, is a rare urogenital congenital disorder. Because of its rarity, there is no approved standard treatment protocol for preserving or removing the extra testicle, yet orchiopexy is frequently performed as a preferred treatment in most medical facilities.
CASE PRESENTATION
We present a 23-year-old single male with a bilaterally empty scrotum. He was unaware of his condition and had not seen a doctor before being admitted to our surgical unit. During his younger sibling's circumcision by a local circumcisionist (a medical staff member, idealy a nurse, whose duty is to perform circumcision, preferably at home), he saw something different (his emptey scrotum) and came to us with his problem. Laboratory findings revealed severe oligospermia, and tumor markers (Alpha fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase) were negative for malignancy. The patient underwent bilateral herniorrhaphy and orchiopexy of all six testicles (three in each inguinal canal) and had an uneventful recovery.
CLINICAL DISCUSSION
As polyorchidism is not a common problem, its management remains a contentious issue due to the lack of evidence-based consensus. However, with the introduction of new imaging modalities and on-table frozen section biopsy, the decision to continue with orchiopexy or orchiectomy can be easily justified; however, conservative treatment is preferable in cases of no coexisting anomalies, particularly cryptorchidism.
CONCLUSION
Polyorchidism could run unnoticed for years, especially if there is no direct and consistent access to a medical facility. In cases where polyorchidism is detected accidentally by imaging or during surgical exploration, the treatment must be justified accordingly.
PubMed: 38833904
DOI: 10.1016/j.ijscr.2024.109837