Ana Corachán1, Hortensia Ferrero2, Julia Escrig3, Javier Monleon3, Amparo Faus4, Irene Cervelló4, Antonio Pellicer1. 1. Fundación IVI, Instituto Universitario IVI, Universidad de Valencia, Valencia, Spain; Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, Valencia, Spain. 2. Fundación IVI, Instituto Universitario IVI, Universidad de Valencia, Valencia, Spain; Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain. Electronic address: hortensia.ferrero@ivirma.com. 3. Hospital Universitario y Politécnico La Fe, Valencia, Spain. 4. Fundación IVI, Instituto Universitario IVI, Universidad de Valencia, Valencia, Spain.
Abstract
OBJECTIVE: To study the effects of short- and long-term vitamin D treatment on uterine leiomyomas in vivo through cell proliferation, extracellular matrix (ECM) degradation, and apoptosis. DESIGN: Preclinical study of human leiomyoma treatment with vitamin D in an nonhuman animal model. SETTING: Hospital and university laboratories. PATIENT(S)/ANIMAL(S): Human leiomyomas were collected from patients and implanted in ovariectomized NOD-SCID mice. INTERVENTION(S): Mice were treated with vitamin D (0.5 μg/kg/d or 1 μg/kg/d) or vehicle for 21 or 60 days. MAIN OUTCOME MEASURE(S): Vitamin D effect in xenograft tissue was assessed by monitoring tumor size (18F-FDG positron-emission tomography/computerized tomography and macroscopic examination), cell proliferation (immunohistochemistry and quantitative real-time polymerase chain reaction [qRT-PCR]), ECM (Western blot), transforming growth factor (TGF) β3 (qRT-PCR), and apoptosis (Westrn blot and TUNEL). RESULT(S): Short-term treatment with vitamin D did not appear to alter leiomyoma size, based on in vivo monitoring and macroscopic examination. However, long-term high-dose treatment induced a significant reduction in leiomyoma size. Cell proliferation was not decreased in the short term, whereas 1 μg/kg/d vitamin D in the long term significantly reduced proliferation compared with control. Although collagen-I and plasminogen activator inhibitor 1 were not modified by short-term treatment, they were both significantly reduced by long-term high-dose vitamin D. Similarly, long-term high-dose vitamin D significantly reduced TGF-β3 expression. Finally, apoptosis significantly increased with both short- and long-term high-dose vitamin D treatment. CONCLUSION(S): Long-term vitamin D acts as an antiproliferative, antifibrotic, and proapoptotic therapy that provides a safe, nonsurgical therapeutic option for reducing uterine leiomyoma size without side-effects.
OBJECTIVE: To study the effects of short- and long-term vitamin D treatment on uterine leiomyomas in vivo through cell proliferation, extracellular matrix (ECM) degradation, and apoptosis. DESIGN: Preclinical study of humanleiomyoma treatment with vitamin D in an nonhuman animal model. SETTING: Hospital and university laboratories. PATIENT(S)/ANIMAL(S): Humanleiomyomas were collected from patients and implanted in ovariectomized NOD-SCID mice. INTERVENTION(S): Mice were treated with vitamin D (0.5 μg/kg/d or 1 μg/kg/d) or vehicle for 21 or 60 days. MAIN OUTCOME MEASURE(S): Vitamin D effect in xenograft tissue was assessed by monitoring tumor size (18F-FDG positron-emission tomography/computerized tomography and macroscopic examination), cell proliferation (immunohistochemistry and quantitative real-time polymerase chain reaction [qRT-PCR]), ECM (Western blot), transforming growth factor (TGF) β3 (qRT-PCR), and apoptosis (Westrn blot and TUNEL). RESULT(S): Short-term treatment with vitamin D did not appear to alter leiomyoma size, based on in vivo monitoring and macroscopic examination. However, long-term high-dose treatment induced a significant reduction in leiomyoma size. Cell proliferation was not decreased in the short term, whereas 1 μg/kg/d vitamin D in the long term significantly reduced proliferation compared with control. Although collagen-I and plasminogen activator inhibitor 1 were not modified by short-term treatment, they were both significantly reduced by long-term high-dose vitamin D. Similarly, long-term high-dose vitamin D significantly reduced TGF-β3 expression. Finally, apoptosis significantly increased with both short- and long-term high-dose vitamin D treatment. CONCLUSION(S): Long-term vitamin D acts as an antiproliferative, antifibrotic, and proapoptotic therapy that provides a safe, nonsurgical therapeutic option for reducing uterine leiomyoma size without side-effects.
Authors: Qiwei Yang; Michal Ciebiera; Maria Victoria Bariani; Mohamed Ali; Hoda Elkafas; Thomas G Boyer; Ayman Al-Hendy Journal: Endocr Rev Date: 2022-07-13 Impact factor: 25.261