Prepubertal Exposure to Genistein Alleviates Di-(2-ethylhexyl) Phthalate Induced Testicular Oxidative Stress in Adult Rats

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN) is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22) to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw)/day (G), DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450) and their mixture (G + D50, G + D150, G + D450). On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient), testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.

Genistein attenuates di‑(2‑ethylhexyl) phthalate-induced testicular injuries via activation of Nrf2/HO‑1 following prepubertal exposure

“…Similar to various other isoflavones, GEN acts as an anti-oxidant, and thus may alleviate the damaging effects of free radicals in tissues ( 14 , 15 ). GEN also influences multiple biochemical functions in living cells, including activation of PPARs, inhibition of several tyrosine kinases, activation of Nrf2 anti-oxidative response and stimulation of autophagy ( 19 , 28 ). Theoretically, we can predict the effects of exposure to multiple EDCs and the mechanisms involved based on previous studies, however the co-administration multiple EDCs may not follow classical dose-responses and the health effects may differ from what would be expected by simply adding or subtracting the effects of individual components.…”

“…Subsequently, testicular homogenates were centrifuged at 3,500 × g for 5 min at 4°C and the supernatants were collected for further testicular redox state analysis. Total anti-oxidant capacity (T-AOC) ( 26 ), superoxide dismutase (SOD) ( 26 ), GSH peroxidase (GSH-PX) ( 27 ), total GSH ( 28 ), GSSG ( 28 ) and MDA ( 29 ) were evaluated using clinical chemistry assay kits (Nanjing Jiancheng Bioengineering Institute, Nanjing, China) according to the manufacturer's instructions to monitor testicular redox state.…”

Cytotoxic effects of ZnO nanoparticles on mouse testicular cells

“…61,62 In particular, two previous studies 26,27 using exposure protocols based on daily administration of the NPs for 35 days have established that ZnO NPs have cytotoxic actions on testicular germ cells in a dose-dependent manner. In line with these studies, we found that a single systemic injection of ZnO NPs caused alteration in the structure of seminiferous epithelium and the production of morphologically abnormal spermatozoa.…”

Co-exposure to endocrine disruptors: effect of bisphenol A and soy extract on glucose homeostasis and related metabolic disorders in male mice

“…In agreement with our finding, Piotrowska et al (2011) did not find any change in testosterone levels of rats treated with soy isoflavones despite the high dose used and the fact that exposure was during the critical prenatal life to sexual maturity period. In general, some studies have implied that there is an antioxidant potential role of soy isoflavones for improving the inflammatory and oxidative effects of BPA on the gonad (Zhang et al 2014;Bernardo et al 2015), and thus soy isoflavones can maintain proper function of the male reproductive system. In contrary, a few studies have also indicated isoflavones reduced fertility and sperm quality along with a possibly antiandrogenic effect (Meena et al 2017) that cannot be ignored in this context.…”