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.
Highlights
Infertility and gonadal dysfunction are well known side-effects by cancer treatment in males
These findings show the therapeutic effect on total body irradiation (TBI)-induced aspermatogenesis and the recovering disrupted gonadal functions by supplementation with TJ107
A marginal recovery in body weight and all reproductive parameters were observed at day 120, but on day 150 further decreases in all parameters were noted in this group
Summary
Infertility and gonadal dysfunction are well known side-effects by cancer treatment in males. Chemotherapy and radiotherapy are commonly used for cancer treatment, but side effects include temporary or permanent infertility. Around 99.5% of men as reported by previous studies experience permanent infertility who receive12Gy TBI [2] and decrease in spermatogenesis in the seminiferous tubules of mice is caused by lower TBI doses as 5–6 Gy [3, 4]. Mechanism reported through previous studies for infertility in irradiated rodent testes is germ cell-apoptosis [5,6,7]. Lipid peroxidation in the cellular membrane is caused by the generation of reactive oxygen species (ROS) which causes deleterious effects of irradiation in biological systems and thereby causing DNA damage in immature germ cells [8, 9]. In three-month-old rats activation of caspase-3, concomitant with increased expression of caspase-8 and decreased expression of caspase-9 induces germ cell-apoptosis [7]
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