期刊
FERTILITY AND STERILITY
卷 113, 期 1, 页码 205-+出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2019.09.018
关键词
uterine leiomyoma; vitamin D; cell proliferation; extracellular matrix; apoptosis
资金
- Health Institute Carlos II [PI15/00312, PI17/01039]
- Spanish Ministry of Economy and Competitiveness through the Sara Borrell Program [CD15/00057]
- VALi+d Program (Generalitat Valenciana) [ACIF/2016/444]
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 mg/kg/d or 1 mg/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 (F-18-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) beta 3 (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 mg/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-beta 3 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. (C) 2019 by American Society for Reproductive Medicine.)
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