title: Dibutyl phthalate impairs steroidogenesis and a subset of LH-dependent genes in cultured human mural granulosa cell in vitro.
abstract: 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.
authors.affiliation: Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Adir
authors.affiliation: Biology Department, Middlebury College, Middlebury, VT, USA.
authors.forename: Catherine M H
authors.initials: CMH
authors.lastname: Combelles
authors.affiliation: Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Mansur
authors.affiliation: Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Libby
authors.initials: L
authors.lastname: Ophir
authors.affiliation: Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Hourvitz
authors.affiliation: Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Raoul
authors.initials: R
authors.lastname: Orvieto
authors.affiliation: Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Jehoshua
authors.initials: J
authors.lastname: Dor
authors.affiliation: Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel. Electronic address: Ronit.Machtinger@sheba.health.gov.il.
authors.forename: Ronit
authors.initials: R
authors.lastname: Machtinger
mesh_terms: D000328:Adult; D001141:Aromatase / Q000235:genetics; D066259:Betacellulin / Q000235:genetics; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003993:Dibutyl Phthalate / Q000633:toxicity*; D066260:Epiregulin / Q000235:genetics; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone; D010750:Phosphoproteins / Q000235:genetics; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D055815:Young Adult; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C587851:BTC protein, human; D066259:Betacellulin; C587880:EREG protein, human; D066260:Epiregulin; D010750:Phosphoproteins; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000098682:Steroidogenic Acute Regulatory Protein; D003993:Dibutyl Phthalate; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D001141:Aromatase; C561410:CYP19A1 protein, human; D002786:Cholesterol Side-Chain Cleavage Enzyme
keywords: Dibutyl phthalate; EGF–like factors; Endocrine disruptors; Granulosa cells; Steroidogenesis