Uterine fibroid cell cytoskeletal organization is affected by altered G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase signaling

Abstract

Objective: To determine whether cyclic strain affects fibroid cell cytoskeletal organization, proliferation, and collagen synthesis differently than myometrial cells.

Design: A basic science study using primary cultures of patient-matched myometrial and fibroid cells.

Setting: Academic laboratory.

Patient(s): Premenopausal women undergoing myomectomy or hysterectomy for the treatment of symptomatic uterine fibroids.

Intervention(s): Application of uniaxial strain patterns mimicking periovulation, menses, or dysmenorrhea using the Flexcell tension system or static control. Secondarily, inhibition of G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase.

Main outcome measure(s): Cell alignment, cell number, and collagen content.

Result(s): Menses-strained cells demonstrated the most variation in cell alignment, cell proliferation, and procollagen content between myometrial and fibroid cells. Procollagen content decreased in myometrial cells with increasing strain amplitude and decreasing frequency. G protein-coupled estrogen receptor-1 inhibition decreases cellular alignment in the presence of strain.

Conclusion(s): Mechanotransduction affecting cytoskeletal arrangement through the G protein-coupled estrogen receptor-1-phosphatidylinositol 3-kinase pathway is altered in fibroid cells. These results highlight the importance of incorporating mechanical stimulation into the in vitro study of fibroid pathology.

Keywords: GPER1; PI3K; Uterine fibroid; mechanical strain.