Effects of di-n-butyl phthalate on male rat reproduction following pubertal exposure

Abstract

Di-n-butyl phthalate (DBP) is an endocrine-disrupting chemical that has the potential to affect male reproduction. However, the reproductive effects of low-dose DBP are still not well known, especially at the molecular level. In the present study, pubertal male Sprague-Dawley rats were orally administered DBP at a wide range of doses (0.1, 1.0, 10, 100 and 500 mg kg⁻¹ day⁻¹) for 30 days. The selected end points included reproductive organ weights, testicular histopathology and serum hormonal levels. Additionally, proteomic analysis was performed to identify proteins that are differentially expressed as a result of exposure to DBP at low doses (0.1, 1.0 and 10 mg kg⁻¹ day⁻¹). Toxic effects were observed in the high-dose groups, including anomalous development of testes and epididymides, severe atrophy of seminiferous tubules, loss of spermatogenesis and abnormal levels of serum hormones. Treatment with low doses of DBP seemed to exert a 'stimulative effect' on the serum hormones. Proteomics analysis of rat testes showed 20 differentially expressed proteins. Among these proteins, alterations in the expression of HnRNPA2/B1, vimentin and superoxide dismutase 1 (SOD1) were further confirmed by Western blot and immunohistochemistry. Taken together, we conclude that high doses of DBP led to testicular toxicity, and low doses of DBP led to changes in the expression of proteins involved in spermatogenesis as well as changes in the number and function of Sertoli and Leydig cells, although no obvious morphological changes appeared. The identification of these differentially expressed proteins provides important information about the mechanisms underlying the effects of DBP on male rat reproduction.

Dose-dependent short-term study of di-n-butyl phthalate on the testicular antioxidant system of Wistar rats

“…Similar observations were reported by Zhou et al (2010) where activities of SOD decreased at 250 and 500 mg/kg/day DBP, although increase was also reported after 100 mg/kg/day. Contrary to the present study, increased expression of oxidative stress protein SOD1 (Cu-ZnSOD) after exposure to DBP (0.1, 1.0, 10, 100, and 500 mg/kg/day) for 30 days was reported (Bao et al 2011). Catalase and glutathione peroxidase/reductase (GPx/GR) system are known scavengers for ROS.…”

“…Generation of free radicals (O 2 ·ˉ, OH·, or O·) causes lipid peroxidation leading to oxidative stress overwhelming the antioxidant defense system (Halliwell 2011). Proteomic analysis of testes revealed 20 differentially expressed proteins with 12 proteins involved in cell cycle, spermatogenesis as well as oxidative stress (Bao et al 2011). The expressions of these proteins were affected at low dose of DBP.…”

Effects of Endocrine Disruptors (NP, DBP and BPA) on Sperm Characteristics and Development of IVF Embryos in Pig

“…The results of our study indicate that NP, DBP and BPA alone basically have detrimental effects. These results are consistent with previous studies (Hunt et al, 2003;Gang and Han, 2006;El-Dakdoky and Helal, 2007;Hallmark et al, 2007;Gong et al, 2009;Bao et al, 2011). The present study attempted to evaluate the combination effects of low and high dose mixtures of NP, DBP and BPA on boar sperm characteristics.…”

Phthalate exposure and human semen quality: Results from an infertility clinic in China

“…DBP and DEHP have been shown to affect the structures and functions of Sertoli cells and germ cells in rats, resulting in a decrease in the number of Sertoli cells and secretion of testosterone hormone in the testes. Together with the decrease in testosterone, the dysfunction and decreased number of Sertoli cells results in a reduction in the number of spermatogenic cells (Bao et al, 2011) and premature detachment of round spermatids (Erkekoglu et al, 2011;O'Donnell et al, 1996), consequently reducing sperm production or increasing abnormal sperm morphology. In agreement with our findings, some studies of rats have reported adverse effects of DBP exposure on sperm production (Bao et al, 2011;Foster et al, 2001) and of DEHP on sperm morphology (Agarwal et al, 1985;Erkekoglu et al, 2011).…”