Abstract
BackgroundWhole body heat stress had detrimental effect on male reproductive function. It's known that the nuclear factor erythroid 2-related factor 2 (Nrf2) activates expression of cytoprotective genes to enable cell adaptation to protect against oxidative stress. However, it’s still unclear about the exactly effects of Nrf2 on the testis. Here, we investigate the protective effect of Nrf2 on whole body heat stress-induced oxidative damage in mouse testis.MethodsMale mice were exposed to the elevated ambient temperature (42°C) daily for 2 h. During the period of twelve consecutive days, mice were sacrificed on days 1, 2, 4, 8 and 12 immediately following heat exposure. Testes weight, enzymatic antioxidant activities and concentrations of malondialdehyde (MDA) and glutathione (GSH) in the testes were determined and immunohistochemical detection of Nrf2 protein and mRNA expression of Nrf2-regulated genes were analyzed to assess the status of Nrf2-antioxidant system.ResultsHeat-exposed mice presented significant increases in rectal, scrotal surface and body surface temperature. The concentrations of cortisol and testosterone in serum fluctuated with the number of exposed days. There were significant decrease in testes weight and relative testes weight on day 12 compared with those on other days, but significant increases in catalase (CAT) activity on day 1 and GSH level on day 4 compared with control group. The activities of total superoxide dismutase (T-SOD) and copper-zinc SOD (CuZn-SOD) increased significantly on days 8 and 12. Moreover, prominent nuclear accumulation of Nrf2 protein was observed in Leydig cells on day 2, accompanying with up-regulated mRNA levels of Nrf2-regulated genes such as Nrf2, heme oxygenase 1 (HO-1), γ-Glutamylcysteine synthetase (GCLC) and NAD (P) H: quinone oxidoreductase 1 (NQO1)) in heat-treated groups.ConclusionsThese results suggest that Nrf2 displayed nuclear accumulation and protective activity in the process of heat treated-induced oxidative stress in mouse testes, indicating that Nrf2 might be a potential target for new drugs designed to protect germ cell and Leydig cell from oxidative stress.
Highlights
Whole body heat stress had detrimental effect on male reproductive function
These results suggest that nuclear factor erythroid 2-related factor 2 (Nrf2) displayed nuclear accumulation and protective activity in the process of heat treated-induced oxidative stress in mouse testes, indicating that Nrf2 might be a potential target for new drugs designed to protect germ cell and Leydig cell from oxidative stress
Assessment of heat treatment Mice rectal surface, scrotal surface and body surface temperatures were significantly increased after 2 h heat exposure at all five time points (Figure 1C, Figure 1D and Figure 2)
Summary
Whole body heat stress had detrimental effect on male reproductive function. It's known that the nuclear factor erythroid 2-related factor 2 (Nrf2) activates expression of cytoprotective genes to enable cell adaptation to protect against oxidative stress. It’s still unclear about the exactly effects of Nrf on the testis. We investigate the protective effect of Nrf on whole body heat stress-induced oxidative damage in mouse testis. The testes normally complete descent into a scrotum before birth to provide a lower temperature for spermatogenesis [1]. If descent does not occur and testis remains in abdomen, it’s described as the cryptorchidism which present invariably sterile and spermatogenesis does not begin until testis is surgically moved into the scrotum [2]. Testes suspend in a scrotum outside the body cavity, spermatogenesis is still disturbed by exposure to high ambient temperature via weakening the ability of thermoregulatory system and inducing increased temperature in testis. The correction or prevention of whole body heat stress-induced sterility is a problem of major concern
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