Di‐(2‐Ethylhexyl) Phthalate Increases Obesity‐Induced Damage to the Male Reproductive System in Mice

Abstract

Objective This study evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) and obesity on male reproductive organ function in male mice and the potential mechanism of male secondary hypogonadism (SH) in such mice. Methods 140 mice were assigned to six groups for 12 weeks: normal, DEHP, DIO, DIO + DEHP low, DIO + DEHP middle, and DIO + DEHP high. The effects of DEHP and obesity upon the reproductive organs were determined by measuring sperm count and motility, relative testis and epididymis weight, hormone level, and pathological changes. Oxidative stress was evaluated by determining malondialdehyde, T-AOC, SOD, GSH, H2O2, CAT, and GSH-PX in testicular tissues. Nrf2 and Keap1 protein were measured by Western blotting. Results DEHP and obesity reduced sperm count and motility, relative testis and epididymis weight, and testosterone level but increased the levels of MDA, H2O2, leptin, and estradiol. Pathological injury was observed in the testicular Leydig cells. Moreover, the activity of CAT, SOD, and GSH-Px enzymes was inhibited. Nrf2 protein expression was reduced but that of Keap1 was increased. Conclusions DEHP and obesity jointly caused damage to male productive function. Oxidative stress in testicular tissue, and a high level of leptin, may provide some evidence to clarify the mechanisms of male SH with DEHP and obesity.

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

“…In addition, our results showed that treatment of cells with DEHP induced over generation of intracellular ROS that leads to a disturbance of redox status balance in cells. In agreement with our studies, a significant increase in ROS generation was observed in vivo and in vitro studies following DEHP treatment . ROS overproduction observed in this work is an index of oxidative stress installation that could be the result of the antioxidant system incapacity to neutralize the ROS overproduction.…”

“…As expected, in the present study, the MTT assay indicated that Abbreviations: GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HO-1, heme oxygenase-1; Nrf2, NF-E2 related factor 2. significant increase in ROS generation was observed in vivo and in vitro studies following DEHP treatment. [44][45][46] ROS overproduction observed in this work is an index of oxidative stress installation that could be the result of the antioxidant system incapacity to neutralize the ROS overproduction. In our study, compared with those of the control group, the activities of SOD and CAT increased significantly in DEHP treated cells.…”

“…Interestingly, similar mechanisms of action were observed by Zhang et al, who showed that the DEHP treatment‐induced testicular injuries in prepubertal mal Sprague‐Dawly rats through the inhibition of the Nrf2‐HO‐1 pathway. Another study from Zhao et al showed a reduction in the Nrf2 expression in testis and epididymis of mice treated with the DEHP.…”

Di (2‐ethylhexyl) phthalate targets the thioredoxin system and the oxidative branch of the pentose phosphate pathway in liver of Balb/c mice

“…Nevertheless, these increases were insufficient to protect the liver from free radicals. In agreement with our studies, a significant increase in oxidative stress generation was observed in vivo and in vitro studies following DEHP treatment …”

Cross Sectional Study on Exposure to BPA and Phthalates and Semen Parameters in Men Attending a Fertility Center

“…The exclusion criteria were: self-reported endocrine diseases (e.g., adrenal disorders with clear etiology), self-reported clinical conditions that could affect semen quality (e.g., testis injury, vasectomy, epididymitis, orchiditis, varicocele), inability to produce a useful semen sample (e.g., azoospermia), missed urine samples, creatinuria out of the World Health Organization (WHO) range of normality for biological monitoring [53]. Using these criteria, the starting population was reduced to 105 men.…”