Autophagy up-regulation by ulipristal acetate as a novel target mechanism in the treatment of uterine leiomyoma: an in vitro study

Ulipristal acetate (UPA) stimulates the autophagic response in primary cultured leiomyoma cells, whereas in matched myometrial cells autophagy remains un- changed after UPA treatment.

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Volume 112, Issue 6, Pages 1150–1159

Authors:

Barbara Del Bello, Ph.D., Paola Marcolongo, Ph.D., Pasquapina Ciarmela, Ph.D., Flavia Sorbi, M.D., Felice Petraglia, M.D., Stefano Luisi, M.D., Ph.D., Emilia Maellaro, Ph.D.

Abstract:

Objective

To assess the effect of ulipristal acetate (UPA) on the autophagic process of uterine leiomyoma cells.

Design

In vitro study in primary cultures of leiomyoma and myometrial cells isolated from biopsy specimen, and gene expression evaluation in biopsy material.

Setting

Cellular pathology laboratory.

Patient(s)

Premenopausal women (without hormonal treatment) undergoing myomectomy or hysterectomy for symptomatic leiomyomas.

Intervention(s)

Surgical specimens collected from uterine leiomyomas and matched normal myometria.

Main Outcome Measure(s)

After treatment of myometrial and leiomyoma cells with UPA, autophagy was evaluated by Western blot analysis of the typical biochemical markers, LC3-II, LC3-II:LC3-I ratio, and p62/SQSTM1. The expression level of Atg7 and Atg4D proteins was also assessed by Western blot.

Result(s)

The increase of LC3-II protein, LC3-II:LC3-I ratio, and p62/SQSTM1 protein indicates that UPA treatment up-regulates the autophagic response in leiomyoma cells, whereas these markers were almost unchanged in myometrial cells. Consistently, an increased level of Atg7 and Atg4D proteins was observed only in UPA-treated leiomyoma cells. The autophagic machinery is put into motion selectively in these cells, despite that the basal messenger RNA levels of LC3SQSTM1, and ATG7 in leiomyoma biopsy specimen were not significantly different from those found in normal myometrial biopsy material.

Conclusion(s)

In vitro UPA treatment stimulates the autophagic response selectively in leiomyoma cells, which adds a novel indication for the clinical use of this selective P receptor (PR) modulator. Autophagy up-regulation may potentially contribute to the leiomyoma shrinkage occurring in UPA-treated patients and warrants further study.


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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