Totally extraperitoneal laparoscopy-assisted microsurgical vasovasostomy for the treatment of obstructive azoospermia caused by pediatric bilateral inguinal herniorrhaphy.

BACKGROUND: Pediatric inguinal hernia repair (IHR) is a common cause of obstructive azoospermia (OA). Yet, the surgical treatment for this kind of OA remains difficult with poor fertility outcome. OBJECTIVES: To evaluate the safety and effectiveness of totally extraperitoneal laparoscopy-assisted microsurgical vasovasostomy (VV) in the treatment of OA caused by pediatric bilateral IHR. MATERIALS AND METHODS: Totally, 37 patients with OA caused by pediatric bilateral IHR were enrolled in this study from March 2015 to December 2020 in Shanghai General Hospital. The clinical data and fertility outcomes were collected and analyzed. RESULTS: All patients enrolled had a history of bilateral IHR at the age of 1-10 years old. The mean age of patients was 27 ± 4.31 (range: 18-35) years. Totally extraperitoneal laparoscopy (TEP) was applied in 31 patients for the exploration and retrieval of pelvic vas deferens end, and 30 of them underwent microsurgical VV successfully. Among the six cases where TEP was not applied, five cases underwent microsurgical anastomosis. Intraoperative exploration revealed that the location of vas deferens injuries included scrotum (2.70%, 1/37), inguinal canal (5.41%, 2/37), pelvic cavity (78.37%, 29/37), and multiple sites (13.51%, 5/37). The mean operation time was 339 ± 96.73 min (range: 130-510 min). There were no surgical complications. Thirty-three cases were followed up for 5-48 months with four cases lost to follow-up. The overall patency rate, pregnancy rate, and natural pregnancy rate were 75.86% (22/29), 46.67% (14/30), and 36.84% (7/19, 3 patients without family planning), respectively. And seven couples conceived through the assisted reproductive technique, two of which using fresh sperm in the ejaculate. CONCLUSION: TEP laparoscopy-assisted microscopic VV is an effective treatment for patients with OA caused by pediatric bilateral IHR.

Effectively synthesized functional Si-doped carbon dots with the applications in tyrosinase detection and lysosomal imaging.

There has been significant interest in the preparation and versatile applications of carbon dots (CDs) due to their immense potential value in sensors and imaging. In this work, silicon-doped green carbon dots (Si-CDs) with high quantum yield and rich epoxypropyl were effectively synthesized. Given the clinical diagnostic importance of abnormal levels of tyrosinase (TYR), sensitive detection of TYR is significant for clinical research. A fluorescence signal-off strategy with Si-CDs as probe was constructed to determine TYR based on the oxidation of dopamine by TYR. The detection ranges of this method were 0.01-1.5 and 10-30 U/mL with the detection limit of 0.0046 U/mL, the lower limit of quantification (LLOQ) was 0.01 U/mL, and TYR was successfully and accurately monitored in human serum. Additionally, due to the role of lysosomes in cellular regulatory processes, including TYR levels and fluorescence stability characteristics of Si-CDs in acidic conditions, it was envisaged to use Si-CDs as probe to establish real-time monitoring of lysosomes. According to fluorescence colocation analysis, Si-CDs had intrinsic lysosomal targeting ability to HepG2 and L-02 (with Pearson correlation coefficients were 0.90 and 0.91, respectively). The targeting of Si-CDs to lysosomes was due to the acidophilic effect of the epoxypropyl on its surface.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

[The application of multidimensional nursing intervention in postoperative patients with benign prostatic hyperplasia].

OBJECTIVE: Analyze the application effect of multidimensional nursing intervention in postoperative patients with benign prostatic hyperplasia in urology, and explore targeted nursing measures. METHODS: A total of 118 patients who underwent benign prostatic hyperplasia surgery at the Urology Department of Jintan First People's Hospital in Changzhou City from December 2022 to June 2023 were selected and divided into an experimental group of 59 and an intervention group of 59 according to different nursing measures. Collect IPSS, QoL, SDS, and SAS scores from patients to evaluate their quality of life and psychological changes during hospitalization. RESULTS: The postoperative SAS score of the experimental group patients (54.44 ±2.93) was lower than that of the control group (56.05±2.22), and the predischarge SAS score (46.19 ± 5.56) was lower than that of the control group (51.32 ± 1.48), with statistical significance (P<0.05). The SDS preoperative score (61.53 ± 6.40), postoperative score (54.75 ± 5.13),and pre discharge score (46.71 ± 4.32) of the experimental group patients were lower than preoperative score (67.76 ± 3.44), postoperative score (58.34 ± 3.03), and predischarge score (50.59 ± 2.58) of the control group with statistical significance (P<0.05). The preoperative IPSS score of the experimental group patients (27.97 ± 3.82) was lower than that of the control group (25.49 ± 4.00), and the difference was statistically significant (P<0.05), but there was no significant difference between the two groups after surgery and before discharge. The preoperative QoL score of the experimental group patients (91.90 ± 6.19) was lower than that of the control group (95.17 ± 5.56), and before discharge (105.15 ± 4.66) was higher than that of the control group (101.63 ± 5.66), with a statistically significant difference (P<0.05). CONCLUSION: Multidimensional nursing measures for postoperative patients with benign prostatic hyperplasia can improve their quality of life, reduce psychological pressure, and benefit patients significantly, which is worth further promotion.

[Effect of transurethral thuliumlaser vapoenucleation of the prostate with low-power conventional pulse mode on sexual function in patients with benign prostatic hyperplasia].

OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.

Low-Intensity Pulsed Ultrasound Enhanced Adipose-Derived Stem Cell-Mediated Angiogenesis in the Treatment of Diabetic Erectile Dysfunction through the Piezo-ERK-VEGF Axis.

Objectives: Erectile dysfunction is a major comorbidity of diabetes. Stem cell transplantation is a promising method to treat diabetic erectile dysfunction. In this study, we evaluated whether low-intensity pulsed ultrasound (LIPUS) could enhance the efficacy of adipose-derived stem cells (ADSCs) and investigated the underlying molecular mechanism. Materials and methods. Sixty 8-week-old male Sprague-Dawley rats were randomly divided into the normal control (NC) cohort or the streptozocin-induced diabetic ED cohort, which was further subdivided into DM, ADSC, LIPUS, and ADSC+LIPUS groups. Rats in the ADSC or ADSC+LIPUS group received ADSC intracavernosal injection. Rats in the LIPUS or ADSC+LIPUS group were treated with LIPUS. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were recorded at Day 28 after injection. The corpus cavernosum tissues were harvested and subjected to histologic analysis and ELISA. The effects of LIPUS on proliferation and cytokine secretion capacity of ADSCs were assessed in vitro. RNA sequencing and bioinformatic analysis were applied to predict the mechanism involved, and western blotting and ELISA were used for verification. Results: Rats in the ADSC+LIPUS group achieved significantly higher ICP and ICP/MAP ratios than those in the DM, ADSC, and LIPUS groups. In addition, the amount of cavernous endothelium and cGMP level also increased significantly in the ADSC+LIPUS group. In vitro experiments demonstrated that LIPUS promoted proliferation and cell cycle progression in ADSCs. The excretion of cytokines such as CXCL12, FGF2, and VEGF was also enhanced by LIPUS. Bioinformatic analysis based on RNA sequencing indicated that LIPUS stimulation might activate the MAPK pathway. We confirmed that LIPUS enhanced ADSC VEGF secretion through the Piezo-ERK pathway. Conclusion: LIPUS enhanced the curative effects of ADSCs on diabetic erectile dysfunction through the activation of the Piezo-ERK-VEGF pathway. ADSC transplantation combined with LIPUS could be applied as a synergistic treatment for diabetic ED.

The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial.

BACKGROUND: A recent sham-controlled clinical study has shown that low-intensity pulsed ultrasound twice per week can safely and effectively treat patients with mild-to-moderate erectile dysfunction (ED). However, large-scale clinical trials are needed to verify its efficacy and safety and determine a reasonable treatment interval. AIM: To study whether low-intensity pulsed ultrasound therapy thrice per week is non-inferior to twice per week in patients with mild-to-moderate ED. METHODS: A randomized, open-label, parallel-group, non-inferiority clinical trial was conducted in 7 hospitals in China. A total of 323 patients with mild-to-moderate ED were randomized (1:1) into thrice per week (3/W) and twice per week (2/W) groups. Low-intensity pulsed ultrasound was applied on each side of the penis for 16 sessions. OUTCOMES: The primary outcome was response rate using the minimal clinically important difference in the International Index of Erectile Function (IIEF-EF) score at week 12. Secondary outcomes included Erection Hardness Score (EHS), Sexual Encounter Profile, Global Assessment Question, and Self Esteem and Relationship Questionnaire. RESULTS: Response rates in 3/W and 2/W groups were 62.0% and 62.5%, respectively. Treatment effect in the 3/W group was noninferior to that of the 2/W group, with rate difference lower bound of -0.01% [95% confidence interval -0.11 to 0.10%] within the acceptable margin (-14.0%). No significant difference was found among secondary outcomes. IIEF-EF score showed a significant increase from baseline in the 3/W group (16.8 to 20.7) and 2/W group (17.8 to 21.7), and the percentage of patients with EHS ≥3 increased in the 3/W (54.9% to 84.0%) and 2/W (59.5% to 83.5%) groups. There was no significant difference in response rate between the 2 groups after controlling for strata factors and homogeneous tests. No treatment-related adverse events were reported. CLINICAL IMPLICATIONS: Low-intensity pulsed ultrasound therapy displays similar efficacy and safety for mild-to-moderate ED when administered thrice or twice per week for 16 sessions. This study provides two options to suit patients' needs. STRENGTHS & LIMITATIONS: This is a large-sample, randomized, controlled, noninferiority trial study. Short-term follow-up and mostly younger patients are the main limitations. CONCLUSION: Low-intensity pulsed ultrasound therapy thrice and twice per week showed equivalent therapeutic effects and safety for mild-to-moderate ED in a young and generally healthy population. This therapy warrants further investigation of its potential value in rehabilitation of ED. Chen, H., Li Z., Li X., et al. The Efficacy and Safety of Thrice vs Twice per Week Low-Intensity Pulsed Ultrasound Therapy for Erectile Dysfunction: A Randomized Clinical Trial. J Sex Med 2022;19:1536-1545.

Single-cell transcriptome atlas of the human corpus cavernosum.

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.

Novel bi-allelic variants in KASH5 are associated with meiotic arrest and non-obstructive azoospermia.

KASH5 is an essential component of the LINC (linker of the nucleoskeleton and cytoskeleton) complex that regulates chromosome movements and nuclear envelope (NE) remodeling in mouse spermatocytes during meiosis prophase I, but its expression and function in human cells, as well as its association with male infertility are largely unknown. In this study, a novel heterozygous copy number variation (CNV) (seq [GRCh37] del(19) (19q13.33) chr19: g.49894043-49903011del) and a heterozygous loss of function variant (NM_144688: c.979_980del: p.R327Sfs*21) in human KASH5 were identified in a non-obstructive azoospermia (NOA)-affected patient and in his infertile sister by whole-exome sequencing and CNV array. Spermatogenesis in the proband was arrested at zygotene-like stage with a deficiency in homolog pairing and synapsis. KASH5 protein expression in human spermatocytes was evaluated and reported first in this study. Single-cell RNA sequencing demonstrated that the LINC complex and associated genes in human and mouse shared a similar expression pattern, indicating a conserved mechanism in the regulation of chromosome movements and NE remodeling. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis. Collectively, we have identified novel rare variants within human KASH5 in patients with NOA and meiosis arrest. Our study expands the knowledge of KASH5 and associated proteins in regulating human meiosis prophase I progress and provides new insight into the genetic etiology of NOA.

Electrochemiluminescence Biosensor for Hyaluronidase Based on the Adjustable Electrostatic Interaction between the Surface-Charge-Controllable Nanoparticles and Negatively Charged Electrode.

A novel electrochemiluminescence (ECL) biosensor for hyaluronidase (HAase) based on the adjustable electrostatic interaction between the surface-charge-controllable nanoparticles and negatively charged electrode has been devised. Hyaluronic acid (HA)-coated amino-modified ruthenium bipyridine-doped silica nanoparticles (Ru@SiO2-NH2@HA NPs) have been synthesized and act as ECL indicators, and the surface of this particle is negatively charged because HA contains a large amount of OH- and COO-. The strong electrostatic repulsion between the Ru@SiO2-NH2@HA NPs and negatively charged indium tin oxide (ITO) electrode surface leads to the detection of a low-intensity ECL signal. In the presence of HAase, the HA on the surface of the Ru@SiO2-NH2@HA NPs can be decomposed, and the particles can be transformed into positively charged amino-modified ruthenium bipyridine-doped silica nanoparticles (Ru@SiO2-NH2 NPs), which can be concentrated near the surface of the ITO electrode through electrostatic attraction, and result in the detection of an enhanced ECL signal. The ECL of the system has a good linear relationship with HAase concentration in the range of 2.0-60 U/mL, and the limit of detection was 0.37 U/mL. The designed biosensor had been applied to detect the target in real samples with satisfied results.

Subjective Well-being of Special Education Teachers in China: The Relation of Social Support and Self-Efficacy.

In order to explore the relationship of social support, self-efficacy, and subjective well-being of special education teachers in China, 496 teachers from 67 special education schools were surveyed by questionnaire. We found that (1) the subjective well-being of special education teachers in China was in the medial level. (2) There were significant differences in subjective well-being level among teachers of different genders, teacher position, education background, and teaching age. Male teachers were of higher subjective well-being; subjective well-being of head teachers was lower than those were not head teachers; teachers with the educational background of postgraduate were of higher relaxation and tension than those with junior college educational background; the control scores of emotion and behavior of teachers with teaching age of 3 years and below were significantly lower than those of teachers with teaching age of more than 10 years. (3) Self-efficacy played a partially mediating role in the relationship between social support and subjective well-being of special education teachers. Suggestions to improve the subjective well-being of special education teachers were discussed in the article.

Novel bi-allelic MSH4 variants causes meiotic arrest and non-obstructive azoospermia.

BACKGROUND: Non-obstructive azoospermia (NOA) is one of the most severe type in male infertility, and the genetic causes of NOA with meiotic arrest remain elusive. METHODS: Four Chinese families with NOA participated in the study. We performed whole-exome sequencing (WES) for the four NOA-affected patients in four pedigrees. The candidate causative gene was further verified by Sanger sequencing. Hematoxylin and eosin staining (H&E) and immunohistochemistry (IHC) were carried out to evaluate the stage of spermatogenesis arrested in the patients with NOA. RESULTS: We identified two novel homozygous frameshift mutations of MSH4 and two novel compound heterozygous variants in MSH4 in four pedigrees with NOA. Homozygous loss of function (LoF) variants in MSH4 was identified in the NOA-affected patient (P9359) in a consanguineous Chinese family (NM_002440.4: c.805_812del: p.V269Qfs*15) and one patient with NOA (P21504) in another Chinese family (NM_002440.4: c.2220_2223del:p.K741Rfs*2). Also, compound heterozygous variants in MSH4 were identified in two NOA-affected siblings (P9517 and P9517B) (NM_002440.4: c.G1950A: p.W650X and c.2179delG: p.D727Mfs*11), and the patient with NOA (P9540) (NM_002440.4: c.G244A: p.G82S and c.670delT: p.L224Cfs*3). Histological analysis demonstrated lack of spermatozoa in seminiferous tubules of all patients and IHC showed the spermatogenesis arrested at the meiotic prophase I stage. Consistent with the autosomal recessive mode of inheritance, all of these mutations were inherited from heterozygous parental carriers. CONCLUSIONS: We identified that six novel mutations in MSH4 responsible for meiotic arrest and NOA. And these results provide researchers with a new insight to understand the genetic etiology of NOA and to identify new loci for genetic counselling of NOA.

[Imaging quality of the robotic visualization 4K3D system and its application in microscopic vasectomy reversal in rats].

OBJECTIVE: To quantitatively assess the performance of the new robotic visualization system (Zeiss, KINEVO 900) in terms of visual imaging effect and evaluate its potential application in microscopic vasectomy reversal. METHODS: We made a parallel comparison between the effects of the plane and stereo visual images of KINEVO 900 and optical surgical microscopy (Zeiss, S7), and performed microscopic vasectomy reversal on the rat model using KINEVO 900. RESULTS: Compared with S7, KINEVO 900 provided an even longer working distance (200－625 mm), a 3－4 times larger effective field area and a 1.5－2 times deeper front depth of field with the same working distance of 200 mm. No statistically significant difference was observed in the average anastomosis time and immediate patency rate between the two platforms (P > 0.05). CONCLUSION: The 4K3D video image stream outputted by KINEVO 900 is not inferior to that of the optical surgical microscope represented by S7 and is sufficient for microsurgeries in urology and andrology. More prospective randomized clinical animal experiments are needed to further evaluate its application value in andrology.

Vasal vessel-sparing microsurgical single-armed vasoepididymostomy to epididymal obstructive azoospermia: A retrospective control study.

This study aimed to evaluate the efficacy and safety of vasal vessel-sparing modified single-armed 2-suture longitudinal intussusception vasoepididymostomy (SA-LIVE) to epididymal obstructive azoospermia patients. Forty consecutive epididymal obstructive azoospermia cases, who underwent microsurgical vasoepididymostomy in Shanghai General Hospital from January 2019 to October 2019, were included in this study. Twenty cases underwent SA-LIVE (group A), and 20 cases underwent vasal vessel-sparing SA-LIVE (group B). Until March 2021, the mean follow-up period was 16.9 ± 4.1 (12-23) months. The overall patency rate was 82.5%, and 80% and 85% for group A and group B respectively. The mean time to achieve patency was 4.11 ± 2.74 months. The overall natural pregnancy rate was 51.5%(17/33) at the mean follow-up of 16.9 months. The natural pregnancy rate was 50.0% for group A and 52.9% for group B (p > .05). At the time of 6 months post-operation, the patency rate was 70% for group A and 80% for group B (p = .465); the natural pregnancy rate was 0% for group A and 31.3% for group B (p = .022). Vasal vessel-sparing SA-LIVE is safe and effective to achieve favourable patency and pregnancy rates. Preserving vasal vessel would improve natural pregnancy rate at a very early stage.

RNA-binding protein ELAVL2 plays post-transcriptional roles in the regulation of spermatogonia proliferation and apoptosis.

OBJECTIVES: RNA-binding proteins (RBPs) play essential post-transcriptional roles in regulating spermatogonial stem cells (SSCs) maintenance and differentiation. We identified a conserved and SSCs-enriched RBP ELAVL2 from our single-cell sequencing data, but its function and mechanism in SSCs were unclear. MATERIALS AND METHODS: Expressions of ELAVL2 during human and mouse testis development were validated. Stable C18-4 and TCam-2 cell lines with overexpression and knockdown of ELAVL2 were established, which were applied to proliferation and apoptosis analysis. RNA immunoprecipitation and sequencing were used to identify ELAVL2 targets, and regulatory functions of ELAVL2 on target mRNAs were studied. Proteins interacting with ELAVL2 in human and mouse testes were identified using immunoprecipitation and mass spectrometric, which were validated by in vivo and in vitro experiments. RESULTS: ELAVL2 was testis-enriched and preferentially expressed in human and mouse SSCs. ELAVL2 was down-regulated in NOA patients. ELAVL2 promoted proliferation and inhibited apoptosis of C18-4 and TCam-2 cell lines via activating ERK and AKT pathways. ELAVL2 associated with mRNAs encoding essential regulators of SSCs proliferation and survival, and promoted their protein expression at post-transcriptional level. ELAVL2 interacted with DAZL in vivo and in vitro in both human and mouse testes. CONCLUSIONS: Taken together, these results indicate that ELAVL2 is a conserved SSCs-enriched RBP that down-regulated in NOA, which regulates spermatogonia proliferation and apoptosis by promoting protein expression of targets.

Transverse testicular ectopia associated with persistent Mullerian duct syndrome in infertile male: two case reports and literature review.

Transverse testicular ectopia (TTE) associated with persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism usually unexpectedly found at surgery for cryptorchidism or inguinal hernia in children. Its etiology and prevalence are unclear, although defects in the gene that encodes anti-Mullerian hormone (AMH) or AMH receptor has been generally considered as the major cause. Adult cases of TTE associated with PMDS are even more peculiar, as the adult patients usually present more complex medical history, require more comprehensive medical examination and management. Two adult men with normal karyotype were referred to the urology outpatient clinic for infertility and cryptorchidism. Semen analysis showed both patients were azoospermic. Ultrasound and computed tomography (CT) found both testes were located at the same side of abdominal cavity or pelvic cavity, which was confirmed during the laparoscopic exploration. A tubular structure adhering to the spermatic cord was also found in both cases. Laparoscopic-assisted transabdominal orchiopexy was performed and the tubular mass was removed. Pathological examination confirmed the existence of Mullerian duct, which showed positive immunostaining of the uterus marker genes. The principles of treatment include the restoration of testes, the preservation of fertility, and the prevention of malignancy. Much attention should be payed to avoid damage of fertile testes and vas deferens in the surgery. Long-term postoperative follow-up is necessary for assessment of malignant transformation and infertility.

Bi-allelic SHOC1 loss-of-function mutations cause meiotic arrest and non-obstructive azoospermia.

BACKGROUND: The genetic causes of human idiopathic non-obstructive azoospermia (NOA) with meiotic arrest remain unclear. METHODS: Two Chinese families with infertility participated in the study. In family 1, two brothers were affected by idiopathic NOA. In family 2, the proband was diagnosed with idiopathic NOA, and his elder sister suffered from infertility. Whole-exome sequencing (WES) was conducted in the two patients in family 1, the proband in family 2 and 362 additional sporadic patients with idiopathic NOA. Sanger sequencing was used to verify the WES results. Periodic acid-Schiff (PAS), immunohistochemistry (IHC) and meiotic chromosomal spread analyses were carried out to evaluate the stage of spermatogenesis arrested in the affected cases. RESULTS: We identified compound heterozygous loss of function (LoF) variants of SHOC1 (c.C1582T:p.R528X and c.231_232del:p.L78Sfs*9, respectively) in both affected cases with NOA from family 1. In family 2, homozygous LoF variant in SHOC1 (c.1194delA:p.L400Cfs*7) was identified in the siblings with infertility. PAS, IHC and meiotic chromosomal spread analyses demonstrated that the spermatogenesis was arrested at zygotene stage in the three patients with NOA. Consistent with the autosomal recessive mode of inheritance, all of these SHOC1 variants were inherited from heterozygous parental carriers. Intriguingly, WES of 362 sporadic NOA cases revealed one additional NOA case with a bi-allelic SHOC1 LoF variant (c.1464delT:p.D489Tfs*13). CONCLUSION: To the best of our knowledge, this is the first report identifying SHOC1 as the causative gene for human NOA. Furthermore, our study showed an autosomal recessive mode of inheritance in the NOA caused by SHOC1 deficiency.

Novel Bi-Allelic Variants of FANCM Cause Sertoli Cell-Only Syndrome and Non-Obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is the most severe disease in male infertility, but the genetic causes for the majority of NOA remain unknown. FANCM is a member of Fanconi Anemia (FA) core complex, whose defects are associated with cell hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. It was reported that variants in FANCM (MIM: 609644) might cause azoospermia or oligospermia. However, there is still a lack of evidence to explain the association between different FANCM variants and male infertility phenotypes. Herein, we identified compound heterozygous variants in FANCM in two NOA-affected brothers (c. 1778delG:p. R593Qfs*76 and c. 1663G > T:p. V555F), and a homozygous variant in FANCM (c. 1972C > T:p. R658X) in a sporadic case with NOA, respectively. H&E staining and immunohistochemistry showed Sertoli cell-only Syndrome (SCOS) in the three patients with NOA. Collectively, our study expands the knowledge of variants in FANCM, and provides a new insight to understand the genetic etiology of NOA.