Journal Article
Dibutyl phthalate impairs steroidogenesis and a subset of LH-dependent genes in cultured human mural granulosa cell in vitro
Adir, M; Combelles, CM; Mansur, A; Ophir, L; Hourvitz, A; Orvieto, R; Dor, J; Machtinger, R
Reproductive Toxicology
ISSN: 0890-6238
EISSN: 1873-1708
Reprod Toxicol. 2017, 04; 69:13-18. [Reproductive toxicology (Elmsford, N.Y.)]
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, 0.01μg/mL, 0.1μg/mL, 1μg/mL, 10μg/mL, or 100μg/mL) for 48h were assessed using enzyme-linked immunosorbent assay and qRT-PCR. Treatment with 100μg/mL DBP resulted in significantly lower 17β-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 100μg/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.
Adult; Aromatase/genetics; Betacellulin/genetics; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme/genetics; Dibutyl Phthalate/toxicity; Epiregulin/genetics; Estradiol/metabolism; Granulosa Cells/drug effects/metabolism; Luteinizing Hormone; Phosphoproteins/genetics; Progesterone/metabolism; RNA, Messenger/metabolism; Vascular Endothelial Growth Factor A/genetics; Young Adult; Dibutyl phthalate; EGF–like factors; Endocrine disruptors; Granulosa cells; Steroidogenesis; 2286E5R2KE; 4G7DS2Q64Y; 4TI98Z838E; 9002-67-9
