AB119. A Chinese herbal formula, Wuzi Yanzong Pill, improves spermatogenesis by modulating mitophagy of Sertoli cells

OBJECTIVE: To evaluate the effects of the Chinese herbal formula Wuzi Yanzong Pill (WYP) on the spermatogenesis and mitophagy of Sertoli cells in a rat model. METHODS: Five groups of male Sprague-Dawley rats (n=5 per group) included control group, model group, low-dose WYP group, medium-dose WYP group and high-dose WYP group. They were treated daily with vehicle, multiglycosides of Tripterygium wilfordii Hook f (GTW) either alone (20 mg/kg) or followed by WYP (0.5, 1.0, or 2.0 g/kg daily) respectively for 30 days. The autophagy genes, LC3 and lysosome-associated membrane protein 2 (LAMP-2) expression of Sertoli cell in testis were measured by immunohistochemical staining. The quantification of mitophagy and LC3 immunogold particles in Sertoli cell were observed by transmission electron microscopy. Histopathological alterations in the testis were determined using Johnsen’s score. RESULTS: The toxicity of GTW towards Sertoli cell and spermatogenesis was accompanied by increased LC3 and LAMP-2 expression and decreased Johnsen’s scores in the GTW group compared with the control group. The increased quantification of mitophagy and LC3 immunogold particles in Sertoli cell were observed in the GTW group testis tissue. Oral high-dose WYP administrations to GTW-treated rats effectively alleviated all of the GTW-induced changes on mitophagy in Sertoli cells. Furthermore, Johnsen’s score of the testis increased greatly compared with the model group. CONCLUSIONS: WYP has the ability to improve spermatogenesis, possibly through modulating the mitophagy of Sertoli cells.