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Identifying the BMP Pathway Type II Receptors in Decidualization
Author(s) -
Hamor Clark,
Monsivais Diana,
Matzuk Marty
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.476.9
Subject(s) - decidualization , stromal cell , decidual cells , microbiology and biotechnology , bmpr2 , biology , bone morphogenetic protein , chemistry , endocrinology , medicine , cancer research , genetics , gene , pregnancy , fetus , placenta
Decidualization is a process driven by hormones and growth factors that results in the differentiation of endometrial stromal cells into decidual cells that are capable of supporting a developing embryo. The overall effect of decidualization is the differentiation of the endometrial stromal cells into decidual cells, which facilitate early blastocyst development, placental function and parturition. Despite the importance of decidualization in reproduction, the molecular mechanisms controlling decidualization are not fully understood. Identifying the signaling pathways responsible for decidualization will provide opportunity to enhance the process of decidualization, which can benefit women experiencing infertility, early pregnancy loss or other pregnancy‐related complications. Past research has shown that Bone Morphogenetic Protein (BMP) signaling is one of the mechanisms controlling decidualization, but the roles of each member of this pathway in decidualization are unknown. Identifying the precise genes in the BMP pathway responsible for decidualization will enable us to develop drugs with clinical applications. The BMP signaling pathway is initiated when a BMP dimer associates with a tetrameric complex of two type one (ALK2, ALK3, ALK6) and two type two receptor proteins (BMPR2, ACVR2A, ACVR2B), which then phosphorylate the SMAD1 and SMAD5 transcription factors. Human endometrial stromal cell (HESC) decidualization can be recapitulated in vitro by exposure to progesterone, estrogen and 8‐bromo‐cyclic‐AMP. Using this technique, we performed siRNA experiments in primary cultures of HESC's to determine the roles of various BMP signaling pathway members in decidualization. We found that SMAD1 and SMAD5 transcription factors and the BMPR2 receptor are essential for in vitro HESC cell decidualization. We also identified that ACVR2A and ACVR2B receptors may be playing a redundant role in decidualization as well. These results indicate that the BMP signaling receptor complex responsible for HESC decidualization is controlled by the concerted action of cell surface receptors that act redundantly but require the activity of both SMAD1 and SMAD5 transcription factors. Support or Funding Information NCI P30 CURE Grant (CA125123)IRACDA Training GrantPDEP Burroughs Wellcome Fund This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .