Combined effects of simultaneous exposure to six phthalates and emulsifier glycerol monosterate on male reproductive system in rats.

Human beings are inevitably exposed to ubiquitous phthalate esters (PEs), and simultaneously ingesting high quantities of food emulsifiers via daily diet. Glycerin monostearate (GMS) is a widely used food emulsifier. The purposes of this study were to investigate the combined effects between the mixture of six frequently used PEs (MIXPs) and GMS on male rat reproductive system, and further to explore the underlying mechanisms. Male rats were orally administered either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses with or without GMS (200mg/kg/d) by gavage. The 15-week exposure of MIXPs caused male reproductive toxicity in a dose- and time-dependent manner, including the decrease of serum testosterone and morphological damage of testis. Metabonomics analyses of urine and Western blotting analyses of steroidogenic proteins (StAR, P450scc, CYP17A1, 17β-HSD and P450arom) indicated that MIXPs exposure down-regulated the expression of steroidogenic proteins, and might alter androgen metabolism. The results also showed that the presence of GMS exacerbated the toxicities of MIXPs to male rat reproductive system. These findings suggest that food emulsifier GMS could enhance the toxic effects of MIXPs on male hormone biosynthesis.