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      Activation of the MAPK/ERK Cell-Signaling Pathway in Uterine Smooth Muscle Cells of Women With Adenomyosis.

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          Abstract

          We investigated whether the myometrium might be intrinsically different in women with adenomyosis. We studied whether the mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPKs/ERKs) and phosphoinositide 3-kinase/mammalian target of rapamycin/AKT (PI3K/mTOR/AKT) cell-signaling pathways, implicated in the pathogenesis of endometriosis, might also be activated in uterine smooth muscle cells (uSMCs) of women with adenomyosis and measured the production of reactive oxygen species (ROS), proinflammatory mediators that modulate cell proliferation and have been shown to activate the MAPK/ERK pathway in endometriosis. The uSMC cultures were derived from myometrium biopsies obtained during hysterectomy or myomectomy in women with adenomyosis and controls with leiomyoma. Proliferation of uSMCs and in vitro activation of the MAPK/ERK cell-signaling pathway were increased in women with adenomyosis compared to controls. The activation of the PI3K/mTOR/AKT pathway was not significant. The ROS production and ROS detoxification pathways were not different between uSMCs of women with adenomyosis and controls suggesting an ROS-independent activation of the MAPK/ERK pathway. Our results also provide evidence that protein kinase inhibitors and the rapanalogue temsirolimus can control proliferation of uSMCs in vitro suggesting an implication of the MAPK/ERK and the PI3K/mTOR/AKT pathways in proliferation of uSMCs in women with adenomyosis and leiomyomas.

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          Author and article information

          Journal
          Reprod Sci
          Reproductive sciences (Thousand Oaks, Calif.)
          SAGE Publications
          1933-7205
          1933-7191
          Dec 2015
          : 22
          : 12
          Affiliations
          [1 ] Department of Gynaecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Paris, France Department of Development, Reproduction and Cancer, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), Paris, France. Department of Gynaecology and Obstetrics, Unit for Reproductive Medicine and Gynaecological Endocrinology, University Hospitals of Geneva and the Faculty of Medicine of the Geneva University, Geneva, Switzerland Laboratory of Immunology, Groupe Hospitalier Cochin, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
          [2 ] Department of Gynaecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Paris, France Department of Development, Reproduction and Cancer, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), Paris, France. Laboratory of Immunology, Groupe Hospitalier Cochin, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
          [3 ] Department of Development, Reproduction and Cancer, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), Paris, France. Laboratory of Immunology, Groupe Hospitalier Cochin, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
          [4 ] Department of Gynaecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Universitaire (GHU) Ouest, Centre Hospitalier Universitaire (CHU) Cochin, Paris, France.
          [5 ] Department of Development, Reproduction and Cancer, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), Paris, France. Laboratory of Immunology, Groupe Hospitalier Cochin, Université Paris Descartes, Sorbonne Paris Cité, Paris, France frederic.batteux@cch.aphp.fr batteux@gmail.com.
          Article
          1933719115589410
          10.1177/1933719115589410
          26071388

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