In vitro exposure of human luteinized mural granulosa cells to dibutyl phthalate affects global gene expression

Michal Adir, Mali Salmon-Divon, Catherine M.H. Combelles, Abdallah Mansur, Yoram Cohen, Ronit Machtinger

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Exposure to dibutyl phthalate (DBP) is ubiquitous among women of reproductive age. Previous studies in animal models and in human cells in vitro have shown that exposure to DBP disrupts ovarian function. Here, we examined the effect of DBP on global gene expression in mural granulosa cells (MGCs) in vitro. Primary cultures of MGC obtained from 48 patients undergoing IVF were treated with increasing concentrations of DBP (0, 0.01, 0.1, 1, 10, or 100 mg/ml) for 48 h. Microarray analysis was used to identify genes exhibiting expression changes following DBP exposure. When compared with untreated cells, exposure to 100 mg/ml DBP resulted in significant differences in expression of 346 annotated genes ( > 2-fold; q value < .05). Of them, 151 were upregulated and 195 downregulated. The main functional annotations affected by DBP were associated with cell cycle, mitosis, Rho GTPases, PLK1, Aurora B signaling pathways, and E2F-mediated regulation of DNA replication. No significant differences in gene expression were observed for the lower concentrations of DBP (0.01, 0.1, 1, and 10 mg/ml) compared with controls for both the microarray analysis and genes validated by quantitative real-time (qRT)-PCR. This study provides important molecular inputs on the effect of short-term DBP exposure on human MGCs in vitro. Our results indicate that acute treatment with high concentrations of DBP alters gene expression pathways mainly associated with the cell cycle.

Original languageEnglish
Pages (from-to)180-188
Number of pages9
JournalToxicological Sciences
Volume160
Issue number1
DOIs
StatePublished - 1 Nov 2017

Keywords

  • Cell cycle
  • Dibutyl phthalate
  • Endocrine disruptors
  • Granulosa cells
  • Microarray transcriptomic analysis

Fingerprint

Dive into the research topics of 'In vitro exposure of human luteinized mural granulosa cells to dibutyl phthalate affects global gene expression'. Together they form a unique fingerprint.

Cite this