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Androgens Modulate the Morphological Characteristics of Human Endometrial Stromal Cells Decidualized In Vitro

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Abstract

The activated androgen receptor (AR) in decidualizing human endometrial stromal cells (HESCs) regulates genes involved in cytoskeletal organization, cell motility, and cell cycle progression. Androgens also enhance the secretion of prolactin, a widely used marker of decidualized HESCs. The purpose of the present study was to investigate the direct effects of androgens on the ultrastructural changes associated with decidual transformation of HESCs. Primary HESC cultures were established and propagated, and confluent cultures were decidualized for 6 days with 8-bromoadenosine 3′,5′-cyclic monophosphate (8-br-cAMP) and progesterone (P4) in the presence or absence of dihydrotestosterone (DHT). Phase-contrast image analysis demonstrated that DHT increases the shape index of decidualizing cells, which was reversed upon cotreatment with the AR antagonist flutamide. Electron microscopy demonstrated that DHT enhances many of the ultrastructural changes induced by 8-br-cAMP and P4 in HESCs. Decidualizing cells are characterized by an abundant cytoplasm, multiple cell surface projections and, unlike undifferentiated HESCs, form 2 or more cell layers. The DHT further stimulated cytoplasmic expansion, lipid droplet formation, the production of an abundant extracellular matrix, and gap junction formation in decidualized HESCs. The present study demonstrates that androgen signaling has an impact on the morphological and ultrastructural changes associated with the decidual process. Our findings show that androgens promote the development and expansion of cytoplasmic organelles and gap junctions in decidualizing HESCs. These results suggest that androgens in early pregnancy play an important role in promoting the cellular transformation associated with decidualization.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Saitama Medical University, 38, Morohongo, Moroyama, Iruma-gun, Saitama, Japan

    Takeshi Kajihara MD, PhD, Hideno Tochigi MD, Japarath Prechapanich MD, Satomi Uchino, Atsuo Itakura MD, PhD & Osamu Ishihara MD, PhD

  2. Division of Morphological Science, Biomedical Research Center, Saitama Medical University, Saitama, Japan

    Kayoko Tanaka

  3. Nihon Medical School, Chiba Hokuso Hospital, Chiba, Japan

    Tatsuo Oguro PhD

  4. Division of Reproductive Health, Warwick Medical School, Clinical Sciences Research Laboratories, University Hospital, Coventry, U.K.

    Sandra Šućurović, Keisuke Murakami MD & Jan J. Brosens MD, PhD

  5. Department of Physiology and Immunology, Medical School, University of Rijeka, Rijeka, Croatia

    Sandra Šućurović

Authors
  1. Takeshi Kajihara MD, PhD
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  2. Kayoko Tanaka
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  3. Tatsuo Oguro PhD
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  4. Hideno Tochigi MD
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  5. Japarath Prechapanich MD
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  6. Satomi Uchino
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  7. Atsuo Itakura MD, PhD
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  8. Sandra Šućurović
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  9. Keisuke Murakami MD
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  10. Jan J. Brosens MD, PhD
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  11. Osamu Ishihara MD, PhD
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Correspondence to Takeshi Kajihara MD, PhD.

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Kajihara, T., Tanaka, K., Oguro, T. et al. Androgens Modulate the Morphological Characteristics of Human Endometrial Stromal Cells Decidualized In Vitro. Reprod. Sci. 21, 372–380 (2014). https://doi.org/10.1177/1933719113497280

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