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

Autores de IIS La Fe

• Roberto González Martín

  Autor

• Andrea Palomar Rios

  Autor

• Yassmin Medina Laver

  Autor

• Alicia Quiñonero Villora

  Autor

• 

  Francisco Domínguez Hernández

  Autor

Grupos

• Biología Reproductiva y Bioingeniería en Reproducción Humana

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. © 2022 by the authors.

Keywords

• Diethylhexyl Phthalate; Endocrine Disruptors; Endometriosis; Endometrium; Female; Histone Demethylases; Humans; Interleukin-6; Membrane Proteins; Phthalic Acids; Receptors, Progesterone; Receptors, Steroid; Vascular Endothelial Growth Factor A; estrogen receptor alpha; estrogen receptor beta; homeobox protein Hox-A10; interleukin 6; lysine specific demethylase 1; pgrmc1 protein; phthalic acid bis(2 ethylhexyl) ester; progesterone receptor B; progesterone receptor t; protein; steroid receptor; transcription factor EZH2; unclassified drug; vasculotropin A; endocrine disruptor; histone demethylase; interleukin 6; membrane protein; PGRMC1 protein, human; phthalic acid; phthalic acid derivative; progesterone receptor; steroid receptor; vasculotropin A; Article; cell invasion; cell viability; controlled study; drug exposure; endometriosis; endometrium cell; female; gene expression; human; human cell; in vitro study; Ishikawa cell line; oocyte donor; phenotype; protein expression; stroma cell