Endometrial Cells Acutely Exposed to Phthalates In Vitro Do Not Phenocopy Endometriosis

Abstract

Environmental factors that have been linked to an increased endometriosis risk include exposure to di-(2-ethylhexyl)-phthalate (DEHP), an endocrine disruptor. This study aims to investigate whether DEHP in vitro exposure in primary endometrial stromal cells (EnSC), primary endometrial epithelial cells (EnEC), and the human endometrial adenocarcinoma cell line Ishikawa properly mimics alterations described in the eutopic endometrium of women with endometriosis. Primary EnSC and EnEC, isolated from six fertile egg donors, and Ishikawa cells were exposed to DEHP (0.1, 1, and 10 µM) and were assessed for viability, endometriosis markers (IL-6, VEGF-A, HOXA10, EZH2, and LSD1), steroid receptor gene expressions (ER-1, ER-2, PR-T, PR-B, and PGRMC1), and invasive capacity. Viability after 72 h of DEHP exposure was not significantly affected. None of the endometriosis markers studied were altered after acute DEHP exposure, nor was the expression of steroid receptors. The invasive capacity of EnSC was significantly increased after 10 µM of DEHP exposure. In conclusion, acute DEHP exposure in primary endometrial cells does not fully phenocopy the changes in the viability, expression of markers, or steroidal receptors described in endometriosis. However, the significant increase in EnSC invasiveness observed after DEHP exposure could be a link between DEHP exposure and increased endometriosis likelihood.

The adverse role of endocrine disrupting chemicals in the reproductive system

“…Furthermore, treatment of endometrial cells with DEHP may increase extracellular signal-regulated kinase phosphorylation and regulate Pak4 expression collaborate with the increase in migration and invasion of endometrial cells, and therefore with the development of EMs ( 70 ). The significant increase in endometrial stromal cells invasiveness observed after DEHP exposure could be a link between DEHP exposure and increased EMs likelihood ( 71 ). Additionally, nonobese diabetic/severe combined immunodeficiency mice fed with DEHP have exhibited greater growth and proliferation of endometrial implants compared to those fed with a vehicle ( 70 ).…”