ISSN 1518 0557
Differential regulatory effect of progesterone on the proliferation and apoptosis of uterine leiomyoma tissue explants and primary leiomyoma cell cultures

2021; 25
Dmitry Voronin, Natalia Sotnikova, Kirill Rukavishnikov, Anna Malyshkina, Sergey Nagornii, Yulia Antsiferova
JBRA Assist. Reprod. 2021; 25 (4):540-548

Received October 10, 2020
Accepted April 14, 2021
Abstract

Background: The growth of uterine leiomyoma is regulated by progesterone, but molecular mechanisms of its action are not fully understood. Materials and Methods: Primary leiomyoma cells were isolated by standard method from 16 samples of uterine leiomyoma tissue. The uterine leiomyoma explants and primary leiomyoma cell cultures were exposed to progesterone in concentrations 0.01 μg/ml, 0.1 μg/ml and 1 μg/ml for 24 h. To assess cell apoptosis the Annexin V test was performed in cell cultures by flow cytometry. The expression of PR-A, PR-B, Ki67, Akt, ERK, PTEN and PPARγ mRNAs was estimated in leiomyoma cells culture and tissue explants by real time RT-PCR. Results: Progesterone treatment promoted viability and proliferation of leiomyoma cell cultures in dose-depended manner. Low and high doses of progesterone decreased early apoptosis of leiomyoma cells, high concentration of progesterone increased the number of living cells in Annexin V-test. Both in leiomyoma cell cultures and tissue explants high doses of progesterone increased the expression of Ki67 mRNA, low doses - the expression of PR-A mRNA. In cell cultures progesterone in low concentration increased the expression of PR-B mRNA and in dose-depended manner - the expression of PTEN and PPARγ mRNAs. Exposure of leiomyoma tissue explants to progesterone led to the increase of PR-B and ERK mRNAs expression in dose-depended manner. Conclusion: It was found that progesterone action on leiomyoma cells apoptosis and proliferation was dose-dependent and different in cell cultures and leiomyoma explants, which can be supposedly explained by the tumor microenvironment influence.


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doi: 10.5935/1518-0557.20210017

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