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Fertil Steril. 2020 Jan;113(1):205-216.e4. doi: 10.1016/j.fertnstert.2019.09.018. Epub 2019 Nov 15.

Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model.

Author information

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.

KEYWORDS:

apoptosis; cell proliferation; extracellular matrix; uterine leiomyoma; vitamin D

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