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BMC Women's Health
Published in: BMC Women's Health 1/2019

Open Access 01-12-2019 | Progesterone | Research article

Myometrial progesterone hyper-responsiveness associated with increased risk of human uterine fibroids

Authors: Mona Omar, Archana Laknaur, Ayman Al-Hendy, Qiwei Yang

Published in: BMC Women's Health | Issue 1/2019

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Abstract

Background

Uterine Fibroids (UFs) growth is ovarian steroid-dependent. Previous studies have shown that estrogen and progesterone play an important role in UF development. However, the mechanism underlying progesterone induced UF pathogenesis is largely unknown. In this study, we determined the expression of progesterone receptor and compared the expression level of progesterone-regulated genes (PRGs) in human myometrial cells from normal uteri (MyoN) versus uteri with UFs (MyoF) in response to progesterone.

Methods

Primary human myometrial cells were isolated from premenopausal patients with structurally normal uteri (PrMyoN). Primary human myometrial cells were also isolated from uterus with UFs (PrMyoF). Isolated tissues were excised at least 2 cm from the closest UFs lesion(s). Progesterone receptor (PR) expression was assessed using Western blot (WB). Expression levels of 15 PRGs were measured by qRT-PCR in PrMyoN and PrMyoF cells in the presence or absence of progesterone.

Results

WB analysis revealed higher expression levels of PR in PrMyoF cells as compared to PrMyoN cells. Furthermore, we compared the expression patterns of 15 UF-related PRGs in PrMyoN and PrMyoF primary cells in response to progesterone hormone treatment. Our studies demonstrated that five PRGs including Bcl2, FOXO1A, SCGB2A2, CYP26a1 and MMP11 exhibited significant progesterone-hyper-responsiveness in human PrMyoF cells as compared to PrMyoN cells (P < 0.05). Another seven PRGs, including CIDEC, CANP6, ADHL5, ALDHA1, MT1E, KIK6, HHI showed gain in repression in response to progesterone treatment (P > 0.05). Importantly, these genes play crucial roles in cell proliferation, apoptosis, cell cycle, tissue remodeling and tumorigenesis in the development of UFs.

Conclusion

These data support the idea that progesterone acts as contributing mechanism in the origin of UFs. Identification and analysis of these PRGs will help to further understand the role of progesterone in UF development.
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Metadata
Title
Myometrial progesterone hyper-responsiveness associated with increased risk of human uterine fibroids
Authors
Mona Omar
Archana Laknaur
Ayman Al-Hendy
Qiwei Yang
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Progesterone
Published in
BMC Women's Health / Issue 1/2019
Electronic ISSN: 1472-6874
DOI
https://doi.org/10.1186/s12905-019-0795-1

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