Effects of Phthalate Esters on Human Myometrial and Fibroid Cells: Cell Culture and NOD-SCID Mouse Data.

Abstract

Evidence is growing that phthalate esters play an important role in the pathogenesis of estrogen-dependent gynecologic diseases, especially uterine fibroids. We aimed to investigate whether in vitro treatment with di-(2-ethylhexyl)-phthalate (DEHP) affects angiogenesis, proliferation, and apoptosis in uterine fibroids. To ascertain this, we evaluated vascular endothelial growth factor (VEGF) expression and AKT/ERT phosphorylation and compared the fibroid volume between nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice fed with and without DEHP. VEGF expression was measured using enzyme-linked immunosorbent assay, and AKT/ERK phosphorylation was analyzed by western blot analysis in human myometrial and fibroid cells. The volume of the fibroid tissues implanted to NOD/SCID mice was measured, and the expression of collagen type I protein, Ki-67, proliferating cell nuclear antigen, and B cell lymphoma 2 were analyzed using immunohistochemistry. We could see significant increases in VEGF expression and AKT phosphorylation in human myometrial and fibroid cells treated with DEHP. The volume of the fibroid tissues was significantly increased in NOD/SCID mice fed with DEHP, which was accompanied by increased expression of collagen type I and AKT phosphorylation. Taken together, these results suggest that exposure to phthalate esters may influence uterine fibroid pathogenesis by increasing VEGF and collagen expression and upregulating AKT phosphorylation.

• Authors: Hyun Jin Kim, Sung Hoon Kim, Young Sang Oh, Seung-Ho Heo, Kang-Hyun Kim, Do Young Kim, Sa Ra Lee, Hee Dong Chae
• Journal: Reproductive sciences (Thousand Oaks, Calif.) (Reprod Sci) Vol. 28 Issue 2 Pg. 479-487 (02 2021) ISSN: 1933-7205 [Electronic] United States
• PMID: 33037561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Esters
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Diethylhexyl Phthalate
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Collagen Type I (metabolism)
• Diethylhexyl Phthalate (toxicity)
• Disease Progression
• Esters (toxicity)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Humans
• Leiomyoma (metabolism, pathology)
• Mice, Inbred NOD
• Mice, SCID
• Myometrium (drug effects, metabolism, pathology)
• Neovascularization, Pathologic
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Tumor Cells, Cultured
• Uterine Neoplasms (metabolism, pathology)
• Vascular Endothelial Growth Factor A (metabolism)
• Mice