Oral exposure to DEHP may stimulate prostatic hyperplasia associated with upregulation of COX-2 and L-PGDS expressions in male adult rats.

Di-(2-ethylhexyl) phthalate (DEHP), a typical environmental endocrine disruptor (EED), can disrupt estrogen and androgen secretion and metabolism process, thus inducing dysfunctional reproduction such as impaired gonadal development and spermatogenesis disorder. Prostaglandin synthases (PGS) catalyze various prostaglandins biosynthesis, involved in inflammatory cascade and tumorigenesis. Yet, little is known about how PGS may impact prostatic hyperplasia development and progression. This study concentrates predominantly on the potential prostatic toxicity of DEHP exposure and the mediating role of PGS. In vivo study, adult male rats were administered via oral gavage 30 μg/kg/d, 90 μg/kg/d, 270 μg/kg/d, 810 μg/kg/d DEHP or vehicle for four weeks. The results elucidated that low-dose DEHP may cause the proliferation of the prostate with an increased PCNA/TUNEL ratio. Given the importance of estrogens and androgens in prostatic hyperplasia, our first objective was to evaluate the levels of sex hormones. DEHP improved the ratio of estradiol (E)/testosterone (T) in a dose-dependent manner and upregulated estrogen receptor alpha (ERα) and androgen receptor (AR) expressions. Prostaglandin synthases, including cyclooxygenase-2 (COX-2) and lipocalin-type prostaglandin D synthase (L-PGDS), were significantly upregulated in the ventral prostate. COX-2 and L-PGDS might mediate the tendency of prostatic hyperplasia induced by low-dose DEHP through estradiol/androgen regulation and imbalance between proliferation and apoptosis in vivo. These findings provide the first evidence that prostaglandin synthases contribute to the tendency toward benign prostatic hyperplasia induced by DEHP. Further investigations will have to be performed to facilitate an improved understanding of the role of prostaglandin synthases in DEHP-induced prostatic lesions.