Male infertility remains a major unmet medical challenge, with poorly defined molecular mechanisms and no effective therapies. Here, we identify a stress granule-mediated necroptotic pathway as a key driver of non-obstructive azoospermia, a severe form of male infertility marked by the loss of spermatogenesis. Environmental or physiological stress activates eIF2α kinases, inducing stress granule formation and the recruitment of ZBP1 and RIPK3 into a cytoplasmic complex. This assembly triggers RIPK3 activation, MLKL phosphorylation, and necroptotic death of spermatogonia and Sertoli cells. Genetic ablation of Zbp1 or Ripk3 protects mice from heat-induced testicular degeneration, establishing their essential role in stress-induced testicular damage. Importantly, activation of this pathway is also observed in aged human testes, linking stress-responsive necroptosis to both pathological infertility and the broader process of reproductive aging. These findings reveal an unrecognized mechanism that couples cellular stress responses to regulated cell death in the male reproductive system.

Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury. MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken. On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126. MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.

Purpose: We used a local anesthetic jet injection technique for adult male circumcision. This method eliminates needle use and may decrease the fear of local anesthetic injection used for male circ...

Retrograde ejaculation contributes to male infertility. Pharmacotherapy has a limited role in retrograde ejaculation. Deflux, a viscous substance, consists of two components: dextranomer microspheres and stabilized hyaluronic acid for the treatment of children with vesicoureteral reflux. According to the published articles, the authors described the first case achieved not only restoration of antegrade ejaculation but also followed conception of the spouse after transurethral bladder neck injection of Deflux. A 30-year-old male kept infertile after 3 years of marriage. The patient reported that he could not ejaculate in an antegrade direction after puberty when he reached sexual climax. There was no semen expulsed from the urethral meatus. Medicine prescribed by a local hospital didn’t restore normal ejaculation. Four embryos fertilized by intracytoplasmic sperm injection developed well until transplantation, but none survived. The local reproductive center confirmed that his spouse preserved full capacity of fertility. He was diagnosed as retrograde ejaculation by real-time monitoring of transrectal ultrasound. He received transurethral bladder neck injection of Deflux. One month later, the patient restored antegrade ejaculation and the spouse of the patient conceived. During 18 months of follow-up, no related complications of the surgery have been observed. Transurethral bladder neck injection of Deflux can be considered as an alternative treatment method for retrograde ejaculation, and natural conception is possible thereafter.

Introduction Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of cutaneous port wine capillary malformations, varicose veins, and hemihypertrophy of bone and soft tissues. Aims To report on a rare case of KTS in an adult man manifested by painless urethral bleeding during penile erection briefly review the clinical presentation and management of the genitourinary forms of this syndrome. Methods On presentation, the clinical features of this patient, including medical history, signs and symptoms, and imaging examinations, were recorded. After diagnosis and initial treatment, a literature review of the urethral features of KTS was performed and is discussed in this report. Results A 35-year-old man with KTS presented with painless urethral bleeding during penile erection that was associated with posterior urethral vascular malformations. The coagulation method was used to treat the malformation, and no urethral bleeding or gross hematuria occurred during a postoperative follow-up period of 6 months. Conclusion This case demonstrates that coagulation therapy and careful follow-up can be adequate treatment approaches for urethral features of KTS. However, the long-term efficacy of coagulation for this disorder should be investigated further. Lei H, Guan X, Han H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180–183.

Nutcracker syndrome (NCS) is a rare cause of varicocele and its treatment is still controversial. To summarize the surgical strategy and outcomes of microvascular Doppler (MVD)-assisted microsurgical left spermatic-inferior epigastric vein anastomosis (MLSIEVA) with microsurgical varicocelectomy (MV) at the same incision for treating NCS-associated varicocele. A retrospective analysis of 13 cases of NCS-associated varicocele between July 2018 and January 2022 was performed. A small incision in the body projection corresponding to the deep inguinal ring was chosen as the surgical incision. All patients underwent MLSIEVA and MV with the assistance of MVD. Patients received real-time Doppler ultrasound (DUS) before and after surgery; urine red blood cells and protein were tested, with a follow-up time of 12–53 mo. All patients had no intraoperative complications, and all postoperative symptoms of hematuria or proteinuria, scrotal swelling, and low back pain disappeared. Comparing pre- and postoperative DUS, two patients did not show any improvement in their postoperative measurements. However, in the remaining patients, the internal diameter of the renal vein at the hilum portion and at the aortomesenteric angle portion, as well as their ratio, improved significantly compared with preoperative measurements. No complications or recurrence of varicocele was observed during postoperative follow-up. Our study suggests that MVD-assisted MLSIEVA with MV is feasible with no major short-term complication and effective regarding the treatment of varicocele and NCS. We investigated microsurgery mediated by microultrasound for the treatment of varicocele associated with nutcracker syndrome. We found this procedure to be safe and effective with good long-term results.