Endocrine Abstracts

Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine disruptor that belongs to the group of phthalates. Human exposure to DEHP is ubiquitous, considering its use in plastics and other common consumer products. In vivo and in vitro studies demonstrate its harmful effects on female reproductive system. The aim of this study was to investigate the effects of short term exposure to DEHP on progesterone synthesis in human granulosa cells. The human nonluteinized granulosa cells (HGrC1) were exposed for 48 h to 25 μM DEHP alone or in the presence of 25 μM forskolin (FOR), stimulator of progesterone synthesis. The results showed that exposure to DEHP did not affect the viability of HGrC1 cells. DEHP did not affect basal but decreased FOR-stimulated progesterone production in HGrC1 after 48 h. To clarify the potential mechanism of DEHP-induced decrease in progesterone production in FOR-stimulated HGrC1, we have analyzed the expression of key genes involved in progesterone synthesis. The results showed that DEHP decreased FOR-stimulated mRNA and protein expression of steroidogenic acute regulatory protein, which regulates rate limiting step in progesterone synthesis. Furthermore, the mRNA expression of 3-beta-hydroxysteroid dehydrogenase, an enzyme that converts pregnenolone to progesterone, was downregulated in FOR-stimulated cells after DEHP exposure. These results indicate that short-term exposure to DEHP decreases progesterone production in human granulosa cells, which could have negative impact on ovarian function and fertility. Funding: Science Fund of the Republic of Serbia, program PROMIS, project DETOX, grant number 6062573.