Dibutyl phthalate impairs steroidogenesis and a subset of LH-dependent genes in cultured human mural granulosa cell in vitro

Exposure to di-butyl phthalate (DBP) exerts negative effects on female fertility in animal models, but human studies remain limited. Here, the effects of DBP exposure on mural granulosa cell function were investigated in primary cultures from women undergoing in vitro fertilization. Cultured cells treated with various doses of DBP (0, 0.01 mu g/mL, 0.1 mu g/mL, 1 mu g/mL, 10 mu g/mL, or 100 mu g/mL) for 48 h were assessed using enzyme-linked immunosorbent assay and qRT-PCR. Treatment with 100 mu g/mL DBP resulted in significantly lower 17 beta-estradiol and progesterone production (p < 0.01). It also resulted in altered mRNA expression of steroidogenic, angiogenic, and epidermal growth factor-like growth factor genes: CYP11A1 (p < 0.001), CYP19A1 (aromatase) (p < 0.001), VEGF-A (p < 0.02), BTC (p = 0.009), and EREG (p = 0.04). StAR expression was impaired after exposure to both 10 and 100 mu g/mL (p <0.03 and p <0.001, respectively). Our results indicate that in vitro exposure of granulosa cells to high doses of DBP alters cell functions. (C) 2017 Elsevier Inc. All rights reserved.