Project title: Common phthalate DEHP and women’s reproductive health risk assessment: mechanistic and chronic low-dose exposure studies (DETOX)

Funded by Science Fund of the Republic of Serbia – Program for excellent projects of young researchers-PROMIS. No. 6062573

Project duration: 2020.-2022.

Principal investigator: dr Kristina Pogrmic-Majkic

Objectives: Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate in plastic products. DEHP is a very powerful endocrine disruptor, which alters female reproductive functions. While the effect of DEHP on granulosa cells’ steroidogenesis in animals is well studied, the mechanism of its action in human granulosa cells remains largely unknown. Also, additional challenges are related to the unknown reproductive consequences of chronic, real-life exposure to this endocrine disruptor. Therefore, the overall objective of this proposal is to reveal the mechanism of action of DEHP in human granulosa cells, which is in line with the EU mission for better protection of the health of EU citizens from chemical exposure. This objective will be accomplished by pursuing the following aims: (i) understand the molecular mechanisms of DEHP action in human granulosa cells and (ii) and to reveal the response of human granulosa cells after “real-life” exposure to DEHP (long-term and low dose).

Methodology: To accomplish the goal of the project, two different approaches, mechanistic and chronic exposure studies will be applied. A variety of molecular biology techniques, such as qRT-PCR, ELISA, cytotoxicity assay, Western blot, ChIP together with novel “omics” technology-RNA-sequencing and bioinformatics will be applied.

Expected impact: We expect that, through work on this emerging issue for EU and worldwide, this project will (i) fill the gap in knowledge about DEHP toxicity and identify the potential link between exposure to DEHPand alteration of reproductive potential among women of reproductive age, and (ii) accelerate the scientific competence of young researcher in Serbia.

Keywords: DEHP, endocrine disruptor, granulosa cells, reproduction, toxicology