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

Abstract

To determine if cyclic strain affects fibroid cell cytoskeletal organization, proliferation, and collagen synthesis differently than myometrial cells. Basic science study using primary cultures of patient-matched myometrial and fibroid cells. Academic Laboratory PATIENT(S): Premenopausal women undergoing myomectomy or hysterectomy for the treatment of symptomatic uterine fibroids. Application of uniaxial strain patterns mimicking periovulation, menses, or dysmenorrhea using the Flexcell® tension system or static control. Secondarily, inhibition of G protein-coupled ER1 (GPER1, G36), and phosphatidylinositol 3-kinase (PI3K, Ly294002). Cell alignment, cell number, and collagen content RESULT: (s): Menses-strained cells demonstrated the most variation in cell alignment, cell proliferation, and pro-collagen content between myometrial and fibroid cells. Pro-collagen content decreased in myometrial cells with increasing strain amplitude and decreasing frequency. GPER1 inhibition decreases cellular alignment in the presence of strain. (s): Mechanotransduction affecting cytoskeletal arrangement through the GPER1-PI3K pathway is altered in fibroid cells. These results highlight the importance of incorporating mechanical stimulation into the in vitro study of fibroid pathology.