MSC-derived exosomes mitigate cadmium-induced male reproductive injury by ameliorating DNA damage and autophagic flux.

Cadmium, an environmental toxicant, severely impairs male reproductive functions and currently lacks effective clinical treatments. Mesenchymal stem cell-derived exosomes (MSC-Exos) are increasingly recognized as a potential alternative to whole-cell therapy for tissue injury and regeneration. This study aims to investigate the protective effects of MSC-Exos against cadmium toxicity on male reproduction. Our findings reveal that MSC-Exos treatment significantly promotes spermatogenesis, improves sperm quality, and reduces germ cell apoptosis in cadmium-exposed mice. Mechanistically, MSC-Exos dramatically mitigate cadmium-induced cell apoptosis in a spermatogonia cell line (GC-1 spg) in vitro by reducing DNA damage and promoting autophagic flux. These results suggest that MSC-Exos have a protective effect on cadmium-induced germ cell apoptosis by ameliorating DNA damage and autophagy flux, demonstrating the therapeutic potential of MSC-Exos for cadmium toxicity on male reproduction.

Combination of High Ligation and Intraoperative Embolization using Polidocanol for Treatment of Varicoceles.

Varicoceles are dilated veins within the pampiniform plexus and are relatively common in the general male population. The spermatic vein has many branches in the scrotal segment and then gradually merges into 1-2 trunks after passing through the internal inguinal ring. The key to a successful varicocelectomy is to ligate all the spermatic veins while protecting the testicular arteries and spermatic lymphatic vessels from damage. The small veins, including the branches of spermatic veins and collateral veins, are easily missed for ligation during conventional high ligation of varicocele, which has been suggested as a major cause of postoperative recurrence. Although microsurgery effectively reduces the risk of missing ligation of the spermatic veins during surgery, it has several shortcomings, such as long operation time and a steep learning curve. More importantly, this technique is difficult to carry out in primary hospitals due to the requirement of specialized equipment. Therefore, an attempt to modify the traditional high ligation aiming to reduce the postoperative recurrence rate has been carried out here. The protocol here combines traditional high ligation with intraoperative embolization to seal off the branches of the spermatic vein and collateral veins. We rapidly injected foamed sclerosant into the internal spermatic vein under direct observation after separation of the spermatic vein and then ligated all the veins. The foamed sclerosant through the varicose vein hampers endothelial cell growth, promotes the growth of thrombus and fibrosis, and ultimately forms fibrous streaks that permanently fill the venous. The results showed a more satisfactory effect on reducing the postoperative recurrence rate compared with traditional high ligation. Since this protocol is simple to carry out and has better results in reducing the recurrence rate, this can be an alternative surgical method for the treatment of varicocele, especially in primary hospitals.

Inhibiting Necroptosis of Spermatogonial Stem Cell as a Novel Strategy for Male Fertility Preservation.

Fertility preservation is a common concern for male cancer survivors of reproductive age. However, except for testicular tissue cryopreservation, which is not very effective, there is no feasible and precise therapy capable of protecting spermatogenesis for prepubertal boys before or during gonadotoxic treatment. This study aims to investigate the effects of inhibiting necroptosis of spermatogonial stem cell (SSC) in fertility preservation. Male mice 12 weeks of age were used to establish gonadotoxicity with two intraperitoneal injections of busulfan at a total dose of 40 mg kg-1. The mouse model and the primary cultured mouse SSCs were used to characterize the relationship between necroptosis of SSC and gonadotoxicity. Meanwhile, the effects of an inhibitor of necroptosis pathway, RIPA-56, were observed on day 36 in the mouse model of busulfan-induced gonadotoxicity. We found that the number of SSCs was decreased, but the level of necroptosis was upregulated on day 18 after busulfan treatment in testes from gonadotoxic mice. Further experiments in primary cultured cells showed that the necroptosis caused cell death in busulfan-treated SSCs and could be inhibited by RIPA-56. After suppressing the necroptosis of SSCs, the busulfan-induced mice had a decreased loss of spermatogenic cells as shown by histology and an increased Johnsen's score. Moreover, the quantities of SSCs and epididymal spermatozoa were restored after intervention with RIPA-56, indicating a series of beneficial effects by targeting the necroptosis of SSCs in mice undergoing busulfan treatment. In conclusion, our findings reveal that the necroptosis of SSCs plays a critical role in busulfan-induced gonadotoxicity and may be a potential target for male fertility preservation.