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Reprogramming of the retinoic acid pathway in decidualizing human endometrial stromal cells
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Ozaki, Rie, Kuroda, Keiji, Ikemoto, Yuko, Ochiai, Asako, Matsumoto, Akemi, Kumakiri, Jun, Kitade, Mari, Itakura, Atsuo, Muter, Joanne, Brosens, Jan J. and Takeda, Satoru (2017) Reprogramming of the retinoic acid pathway in decidualizing human endometrial stromal cells. PLoS One, 12 (3). e0173035. doi:10.1371/journal.pone.0173035 ISSN 1932-6203.
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Official URL: http://dx.doi.org/10.1016/journal.pone.0173035
Abstract
Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively. Furthermore, the expression of RAR, the receptor that mediates the pro-apoptotic effects of RA, was also inhibited. By contrast, PPARβ/δ, which transduces the differentiation responses of RA, was upregulated. Decidualization was also associated with increased expression of retinol-binding protein 4 (RBP4) and various enzymes involved in the metabolism of RA and its precursor, retinaldehyde (Rald), including CYP26A1, DHRS3, and RDH12. Exposure of differentiating HESCs to RA or Rald reversed the inhibition of the CRABP2-RAR pathway, perturbed the expression of decidual marker genes and triggered cell death. Taken together, the data demonstrate that decidualizing HESCs silence RA signaling by downregulating key cytoplasmic binding proteins and by increasing retinoid metabolism. However, excessive RA exposure is toxic for decidual cells and triggers a response that may lead to pregnancy failure.
| Item Type: | Journal Article | ||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||
| Journal or Publication Title: | PLoS One | ||||||
| Publisher: | Public Library of Science | ||||||
| ISSN: | 1932-6203 | ||||||
| Official Date: | 2 March 2017 | ||||||
| Dates: |
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| Volume: | 12 | ||||||
| Number: | 3 | ||||||
| Article Number: | e0173035 | ||||||
| DOI: | 10.1371/journal.pone.0173035 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Reuse Statement (publisher, data, author rights): | ** From Europe PMC via Jisc Publications Router. ** Licence for this article: cc by | ||||||
| Access rights to Published version: | Open Access (Creative Commons) |
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