Physiological Adaptation to Simultaneous Chronic Exposure to High-Fat Diet and Dichlorodipheniletylhene (DDE) in Wistar Rat Testis

Abstract

Environmental chemicals can be introduced by consuming contaminated foods. The environmental chemical dichlorodiphenyldichloroethylene (DDE), a persistent metabolite of dichlorodiphenyltrichloroethane (DDT), can affect spermatogenesis. Our study aims to evaluate, by using spectrophotometric analyses, western blot, and immunohistochemistry, the adaptive responses in testis of adult rats treated with a non-toxic dose of DDE, alone or in association with a high-fat diet (HFD). Four experimental groups were performed: N (normal diet); D (HFD); D + DDE (HFD + DDE); N + DDE (normal diet + DDE). D group showed a reduction in antioxidant capacity, and increases in lipid peroxidation, apoptosis, and proliferation associated with morphological impairment. A reduction in androgen receptor (AR) and serum testosterone levels were also found. DDE-treated groups exhibited higher lipid peroxidation levels compared to N and D, associated with pronounced defect in antioxidant capacity, apoptosis, cellular proliferation, as well as with tissue damage. Moreover, decreases in AR and serum testosterone levels were found in DDE-treated groups vs. N and D. In conclusion, HFD and DDE produced cellular stress leading to antioxidant impairment, apoptosis, and decreases in AR and serum testosterone levels associated with tissue damage. Cellular proliferation could be used as an adaptation to counterbalance the occurred damage, maintaining a pool of tubules that follow physiological maturation.

Exposure to Dichlorodiphenyldichloroethylene (DDE) and Metallothionein Levels in Rats Fed with Normocaloric or High-Fat Diet: A Review

“…Indeed, in the rats fed a high-fat diet and in the DDE-administered rats, a marked increase in the MT content was observed in the nuclei of both hepatic and renal cells, with a concomitant drop in the cytoplasmic protein level. The presence of MTs in nuclei occurring through a nuclear translocation of proteins is considered a cellular mechanism engaged to protect DNA from hydroxyl radical attacks [22,57]. Thanks to the ability of these proteins to donate zinc to several enzymes, a high level of nuclear MTs has also been related to the increased zinc requirement for metalloenzymes and transcription factors during fast cellular metabolism and growth [63][64][65][66].…”

“…The treatments also induce lipid peroxidation, a cellular condition previously associated with inhibition of MT synthesis in rat testes [45]. However, the nuclear translocation of MT proteins observed in the hepatocytes of the animals administered DDE or fed a high-fat diet outlines a role of MTs in the protection of DNA from hydroxyl radical attacks [57,58].…”

High-Fish Oil and High-Lard Diets Differently Affect Testicular Antioxidant Defense and Mitochondrial Fusion/Fission Balance in Male Wistar Rats: Potential Protective Effect of ω3 Polyunsaturated Fatty Acids Targeting Mitochondria Dynamics

“…To evaluate the possible correlation between oxidative injury and mitochondrial dynamic behavior, which directly correlates with mitochondrial morphology and function [42], MFN2 and DRP1, the principal proteins involved in the mitochondrial dynamics, were analyzed by western blotting. Results showed that fusion and fission processes change in different way in L and F rats compared to the control animals.…”

“…Moreover, the same authors demonstrated that ω3-PUFAs supplementation in vitro protected Sertoli cells from the harmful effect of palmitic acid, preventing cellular oxidative stress and apoptosis [41]. In our recent work, we found that antioxidant activity plays a key role in the control of cellular stress, apoptosis and tissular damage in rat testis [42]. In fact, we showed that high SFA diet (45% fat) negatively affected antioxidant system in rat testis by inducing malondialdehyde (MDA) accumulation as a product of lipid peroxidation and apoptosis.…”

“…In fact, we showed that high SFA diet (45% fat) negatively affected antioxidant system in rat testis by inducing malondialdehyde (MDA) accumulation as a product of lipid peroxidation and apoptosis. In the same experimental work, simultaneous exposure to high fat diet and environmental pollutants elicited a further rise in oxidative stress and apoptosis, associated with a worsened antioxidant system with a strong reduction in both SODs and GPx activities [42]. Therefore, spermatogenesis was compromised.…”