RRC ID 66002
著者 Simon V, Avet C, Grange-Messent V, Wargnier R, Denoyelle C, Pierre A, Dairou J, Dupret JM, Cohen-Tannoudji J.
タイトル Carbon Black Nanoparticles Inhibit Aromatase Expression and Estradiol Secretion in Human Granulosa Cells Through the ERK1/2 Pathway.
ジャーナル Endocrinology
Abstract Secretion of 17-β-estradiol (E2) by human granulosa cells can be disrupted by various environmental toxicants. In the current study, we investigated whether carbon black nanoparticles (CB NPs) affect the steroidogenic activity of cultured human granulosa cells. The human granulosa cell line KGN and granulosa cells from patients undergoing in vitro fertilization were treated with increasing concentrations of CB NPs (1 to 100 µg/mL) together or not with follicle-stimulating hormone (FSH). We observed that CB NPs are internalized in KGN cells without affecting cell viability. CB NPs could be localized in the cytoplasm, within mitochondria and in association with the outer face of the endoplasmic reticulum membrane. In both cell types, CB NPs reduced in a dose-dependent manner the activity of aromatase enzyme, as reflected by a decrease in E2 secretion. A significant decrease was observed in response to CB NPs concentrations from 25 and 50 µg/mL in KGN cell line and primary cultures, respectively. Furthermore, CB NPs decreased aromatase protein levels in both cells and reduced aromatase transcript levels in KGN cells. CB NPs rapidly activated extracellular signal-regulated kinase 1 and 2 in KGN cells and pharmacological inhibition of this signaling pathway using PD 98059 significantly attenuated the inhibitory effects of CB NPs on CYP19A1 gene expression and aromatase activity. CB NPs also inhibited the stimulatory effect of FSH on aromatase expression and activity. Altogether, our study on cultured ovarian granulosa cells reveals that CB NPs decrease estrogens production and highlights possible detrimental effect of these common NPs on female reproductive health.
巻・号 158(10)
ページ 3200-3211
公開日 2017-10-1
DOI 10.1210/en.2017-00374
PII 3979717
PMID 28977593
MeSH Aromatase / genetics Aromatase / metabolism Aromatase Inhibitors / pharmacology* Cell Line Dose-Response Relationship, Drug Down-Regulation / drug effects Endocrine Disruptors / pharmacology Estradiol / biosynthesis Estradiol / metabolism* Estrogen Antagonists Female Fertilization in Vitro Follicle Stimulating Hormone / administration & dosage Granulosa Cells / chemistry Granulosa Cells / enzymology* Granulosa Cells / metabolism Humans MAP Kinase Signaling System / drug effects* MAP Kinase Signaling System / physiology Nanoparticles / administration & dosage* Nanoparticles / analysis Soot / administration & dosage Soot / analysis Soot / pharmacology*
IF 3.934
リソース情報
ヒト・動物細胞 KGN(RCB1154)