To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.
Humans ; Male ; Sperm Retrieval ; Klinefelter Syndrome ; Microdissection ; Anti-Mullerian Hormone ; Semen ; Testis ; Spermatozoa ; Testosterone ; Azoospermia ; Retrospective Studies

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.
Male ; Humans ; Urethral Stricture/etiology* ; Retrospective Studies ; Constriction, Pathologic/surgery* ; Lichen Sclerosus et Atrophicus/surgery* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; China ; Urethra/surgery* ; Postoperative Complications/etiology* ; Mouth Mucosa ; Diabetes Mellitus/etiology* ; Anticoagulants ; Coronary Disease

This study aimed to evaluate the ability of rete testis thickness (RTT) and testicular shear wave elastography (SWE) to differentiate obstructive azoospermia (OA) from nonobstructive azoospermia (NOA). We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital (Shanghai, China) between August 2019 and October 2021. The testicular volume (TV), SWE, and RTT were compared among patients with OA and NOA and healthy controls. The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve. The TV, SWE, and RTT in OA differed significantly from those in NOA (all P ≤ 0.001) but were similar to those in healthy controls. Males with OA and NOA were similar at TVs of 9-11 cm 3 ( P = 0.838), with sensitivity, specificity, Youden index, and area under the curve of 50.0%, 84.2%, 0.34, and 0.662 (95% confidence interval [CI]: 0.502-0.799), respectively, for SWE cut-off of 3.1 kPa; and 94.1%, 79.2%, 0.74, and 0.904 (95% CI: 0.811-0.996), respectively, for RTT cut-off of 1.6 mm. The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range. In conclusion, ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA, particularly in the TV overlap range.
Male ; Humans ; Azoospermia ; Rete Testis ; China ; Testis

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; MicroRNAs/genetics* ; Signal Transduction/genetics* ; Spermatozoa/metabolism* ; Gene Expression Profiling

Male ; Humans ; Genital Diseases, Male ; Scrotum ; Cysts ; Pelvic Pain ; Retrospective Studies

Vasectomy damage is a common complication of open nonmesh hernia repair. This study was a retrospective analysis of the characteristics and possible causes of vas deferens injuries in patients exhibiting unilateral or bilateral vasal obstruction caused by open nonmesh inguinal herniorrhaphy. The site of the obstructed vas deferens was intraoperatively confirmed. Data, surgical methods, and patient outcomes were examined. The Anderson-Darling test was applied to test for Gaussian distribution of data. Fisher's exact test or Mann-Whitney U test and unpaired t-test were used for statistical analyses. The mean age at operation was 7.23 (standard deviation [s.d.]: 2.09) years and the mean obstructive interval was 17.72 (s.d.: 2.73) years. Crossed (n = 1) and inguinal ( n = 42) vasovasostomies were performed. The overall patency rate was 85.3% (29/34). Among the 43 enrolled patients (mean age: 24.95 [s.d.: 2.20] years), 73 sides of their inguinal regions were explored. The disconnected end of the vas deferens was found in the internal ring on 54 sides (74.0%), was found in the inguinal canal on 16 sides (21.9%), and was found in the pelvic cavity on 3 sides (4.1%). Location of the vas deferens injury did not significantly differ according to age at the time of hernia surgery ( ≥ 12 years or <12 years) or obstructive interval (≥15 years or <15 years). These results underscore that high ligation of the hernial sac warrants extra caution by surgeons during open nonmesh inguinal herniorrhaphy.
Male ; Humans ; Young Adult ; Adult ; Child ; Vas Deferens/surgery* ; Herniorrhaphy/methods* ; Retrospective Studies ; Hernia, Inguinal/surgery* ; Iatrogenic Disease ; Laparoscopy

Primary ciliary dyskinesia (PCD) is a rare hereditary orphan condition that results in variable phenotypes, including infertility. About 50 gene variants are reported in the scientific literature to cause PCD, and among them, dynein axonemal assembly factor 4 ( DNAAF4 ) has been recently reported. DNAAF4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as flagella. In the current study, a single patient belonging to a Chinese family was recruited, having been diagnosed with PCD and asthenoteratozoospermia. The affected individual was a 32-year-old male from a nonconsanguineous family. He also had abnormal spine structure and spinal cord bends at angles diagnosed with scoliosis. Medical reports, laboratory results, and imaging data were investigated. Whole-exome sequencing, Sanger sequencing, immunofluorescence analysis, hematoxylin-eosin staining, and in silico functional analysis, including protein modeling and docking studies, were used. The results identified DNAAF4 disease-related variants and confirmed their pathogenicity. Genetic analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected individual. The identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus, resulting in a truncated and functionless DNAAF4 protein. Immunofluorescence analysis indicated that the inner dynein arm was not present in the sperm flagellum, and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking flagella. The current study found novel biallelic variants causing PCD and asthenoteratozoospermia, extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of asthenoteratozoospermia. These findings will improve our understanding of the etiology of PCD.
Adult ; Humans ; Male ; Asthenozoospermia/genetics* ; Dyneins/genetics* ; East Asian People ; Kartagener Syndrome/genetics* ; Mutation ; Proteins/genetics* ; Semen/metabolism*

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.
Animals ; Humans ; Male ; Female ; Sertoli Cells/metabolism* ; Klinefelter Syndrome/genetics* ; Endothelial Cells ; Testis/metabolism* ; X Chromosome/metabolism* ; Mammals/genetics*

To compare the impact of the scrotal vs inguinal orchidopexy approach on the testicular function of infants with cryptorchidism, a randomized controlled trial was conducted involving boys who were 6-12 months old at surgery and were diagnosed with clinically palpable, inguinal undescended testis. Between June 2021 and December 2021, these boys at Fujian Maternity and Child Health Hospital (Fuzhou, China) and Fujian Children's Hospital (Fuzhou, China) were enrolled. Block randomization with a 1:1 allocation ratio was employed. The primary outcome was testicular function assessed by testicular volume, serum testosterone, anti-Müllerian hormone (AMH), and inhibin B (InhB) levels. Secondary outcomes included operative time, amount of intraoperative bleeding, and postoperative complications. Among 577 screened patients, 100 (17.3%) were considered eligible and enrolled in the study. Of the 100 children who completed the 1-year follow-up, 50 underwent scrotal orchidopexy and 50 underwent inguinal orchidopexy. The testicular volume, serum testosterone, AMH, and InhB levels in both groups increased markedly after surgery (all P < 0.05), but there were no apparent differences between groups at 6 months and 12 months after operation (all P > 0.05). No differences between the scrotal and inguinal groups were noted regarding the operative time ( P = 0.987) and amount of intraoperative bleeding ( P = 0.746). The overall complication rate (2.0%) of the scrotal group was slightly lower than that of the inguinal group (8.0%), although this difference was not statistically significant ( P > 0.05). Both scrotal and inguinal orchiopexy exerted protective effects on testicular function in children with cryptorchidism, with similar operative status and postoperative complications. Scrotal orchiopexy is an effective alternative to inguinal orchiopexy in children with cryptorchidism.
Female ; Pregnancy ; Male ; Infant ; Humans ; Child ; Cryptorchidism/surgery* ; Orchiopexy ; Scrotum/surgery* ; Postoperative Complications ; Anti-Mullerian Hormone ; Testosterone

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.
Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Drug Resistance, Neoplasm/genetics* ; Cell Line, Tumor ; Receptors, Androgen/genetics* ; Nitriles ; Apoptosis