The effectiveness of traditional Japanese medicine Goshajinkigan in irradiation-induced aspermatogenesis in mice

Abstract

BackgroundInfertility and gonadal dysfunction are well known side-effects by cancer treatment in males. In particularly, chemotherapy and radiotherapy induced testicular damage, resulting in prolonged azoospermia. However, information regarding therapeutics to treat spermatogenesis disturbance after cancer treatment is scarce. Recently, we demonstrated that Goshajinkigan, a traditional Japanese medicine, can completely rescue severe busulfan-induced aspermatogenesis in mice. In this study, we aimed to detect the effects of Goshajinkigan on aspermatogenesis after irradiation.MethodsThis is animal research about the effects of traditional Japanese medicine on infertility after cancer treatment. C57BL/6 J male mice received total body irradiation (TBI: a single dose of 6Gy) at 4 weeks of age and after 60 days were reared a Goshajinkigan (TJ107)-containing or TJ107-free control diet from day 60 to day 120. Then, two untreated females were mated with a single male from each experimental group. On day 60, 120 and 150, respectively, the sets of testes and epididymis of the mice in each group after deep anesthetization were removed for histological and cytological examinations.ResultsHistological and histopathological data showed that 6Gy TBI treatment decreased the fertility rate (4/10) in the control diet group; in contrast, in the TJ107-diet group, the fertility rate was 10/10 (p < 0.05 vs. 6Gy group). Supplementation with TJ107 was found to rescue the disrupted inter-Sertoli tight junctions via the normalization of claudin11, occludin, and ZO-1 expression and reduce serum anti-germ cell autoantibodies.ConclusionsThese findings show the therapeutic effect on TBI-induced aspermatogenesis and the recovering disrupted gonadal functions by supplementation with TJ107.

Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis

“…We also suggest that these medicines may act by reducing the testicular inflammation induced by BSF. We have previously demonstrated that impaired reproductive function induced by chemotherapy and radiotherapy was related to immune-pathophysiologies [17,31,32]. In the future, we propose to examine the effects of TJ7 and TJ41 alone or in combination on irradiation-induced spermatogenic defects and to further clarify their mechanisms of action, focusing on testicular immunology.…”

Role of Antioxidant Natural Products in Management of Infertility: A Review of Their Medicinal Potential

“…Gosha-Jink-Gan is a Kampo formula which is known to manage chemotherapy induced peripheral neuropathy [ 155 , 156 ]. Along with the study our research reviewed, it is newly receiving attention as a potential agent to recover spermatogenesis [ 93 , 157 ]. Saikokaryukatsuboreito is also another Kampo medicine, identified to improve spermatogenesis and testosterone levels [ 95 , 158 ].…”

Effects of Chemotherapy and Radiotherapy on Spermatogenesis: The Role of Testicular Immunology

“…Some studies have indicated that irradiation-mediated oxidative stress induces apoptosis primarily in adult mouse and rat germ cells [ 69 , 70 , 71 , 72 ]. Additionally, irradiation-induced germ cell apoptosis depends on activation of caspase-3 in three-month-old rats [ 72 ], concomitant with increased expression of caspase-8 and decreased expression of caspase-9 in adult rats and prepubertal mice, respectively [ 72 , 73 ] ( Table 1 , Figure 1 ). However, irradiation-induced apoptosis does not occur in all types of testicular somatic cells.…”

“…An increase in BTB permeability is known to enhance ASA production, resulting in infertility in males [ 85 , 86 , 98 ]. Recently, we reported that single-dose TBI induced ASA that preferentially reacted with mature spermatids and spermatozoa in prepubertal mice [ 73 ]. Our results showed that 6 Gy of TBI induced a disruption of spermatogenesis with a decrease in inter-Sertoli tight junction mRNA levels and the production of ASA ( Table 1 ).…”

“…In contrast, irradiation treatment induced significant decreases in the weights of the testes and epididymal sperm cell counts on day 30; marginal recovery was observed from day 60 to day 120, but further decreases in all parameters were noted on day 150 ( Figure 2 ). Notably, supplementation with the above oriental medicine significantly restored the epididymal spermatozoa count and fertility on day 150 but not day 120 [ 73 ]. This belated recovery of spermatogenesis in the irradiated group compared with that in the busulfan-treated group suggested that the presence of ASAs may be the other immunological cause of aspermatogenesis.…”