CasesTesticular adrenal rest tumor (TART) is one of the possible causes of male infertility, accompanied by congenital adrenal hyperplasia (CAH). Here are reported two cases of TARTs that were referred to Kobe City Medical Center West Hospital for the treatment of infertility and testicular tumors.OutcomeIn one case, the semen analysis was improved from oligoasthenozoospermia to normozoospermia after taking oral glucocorticoid supplementation. The other case of original azoospermia showed that sperm had ejaculated into the semen after taking oral glucocorticoid supplementation.ConclusionAlthough the prevalence of TARTs in male infertility is very rare, it is important to know how to approach this disease, considering the curable pathology of spermatogenesis and tumors resembling an appearance to germ cell tumors.
Mirabegron is a selective beta3‐adrenoceptor (β3‐AR) agonist, which is commonly used for the treatment of overactive bladder. This medicine is associated with atrophy of reproductive organs in rats. However, no study has examined the detailed action and mechanism of its toxicity in reproductive cells. In this study, we examined the effect of mirabegron on primary cultured rat Sertoli cells. Firstly, RT‐PCR and immunocytochemistry revealed that β3‐AR was present in rat Sertoli cells. Then, primary cultured rat Sertoli cells were treated with mirabegron. Quantitative real‐time PCR revealed that mirabegron treatment induced a significant increase in claudin‐11 mRNA, which is crucial for spermatogenesis. Western blot analysis also showed that mirabegron treatment significantly activated p44/42 mitogen‐activated protein kinase (MAPK). After additional treatment with U0126, a specific noncompetitive inhibitor of mitogen‐activated protein kinase kinase (MAPKK), the upregulation of claudin‐11 mRNA induced by mirabegron was reduced. At the same time, immunocytochemistry showed mirabegron treatment disturbed claudin‐11 localisation to tight junction, which was recovered when treated with mirabegron in the presence of U0126. These results suggest that mirabegron treatment is associated with assembly of the blood–testis barrier through p44/42 MAPK pathway. These findings could explain one of the underlying mechanisms of reproductive toxicity induced by mirabegron.
Four weeks after subcutaneous autograft of LSCs in combination with Sertoli and myoid cells in castrate mice, the cells in graft expressed 3B-HSD, SOX-9 and A-SMA. Serum testosterone in castrated mice that received autograft was significantly higher compared to mice that did not receive autograft (22.4þ/-1.9 VS 11.9þ/-0.8 Ng/DL, p<0.05). Importantly, mice that received LSC autograft maintained production of LH and FSH with levels higher than mice that received testosterone pellet implant (LH 3.09þ/-1.47 VS 0.01þ/-0.01 ng/ml) (FSH 102.6þ/-28.1 VS 51.7þ/-7.4ng/ml) respectively. Furthermore, T levels consistently increased at 15, 30 and 60 days following subcutaneous autograft (12.01þ/-0.87ng/DL (neg CTL) vs 15.1þ/-1.50ng/DL (15 days Autograft) vs 22.26þ/-1.33ng/DL (30 days Autograft) vs 37.3þ/-9.6ng/DL (60 days Autograft)), demonstrating differentiating LSC within the autograft. In addition, we found that levels of 3BHSD were induced upon SAG (DHH inducer) treatment in-vitro conditions. Immunostaining autografts (4 weeks), containing LSCs treated with SAG before subcutaneous implantation, showed higher levels of SOX9, and A-SMA. Importantly, T levels were significantly higher (p<0.05) in mice received SAG treated autografts vs negative controls (23.95þ/-4.11 Ng/DL vs 11.91þ/-0.80 Ng/DL). Collectively these results establish that Hedgehog signalling induces survival of adjacent testicular cells and regulates graft function.CONCLUSIONS: Our results demonstrate that subcutaneous autograft of LSC in combination with Sertoli cells and myoid cells can increase serum testosterone without inhibiting circulating LH and FSH in castrate mice. Extratesticular LSC appear to be regulated by Hedgehog signalling. Leydig stem cell autograft can a novel therapeutic approach to increase serum testosterone while simultaneously preserving hypothalamic-pituitary-gonadal axis. Factors involved in hedgehog signalling can be utilized to enhance graft efficacy.
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