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Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis

Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered signaling pathways during decidualization could identify the underlying cause of infertility and pregnancy complications. Our stud...

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Detalles Bibliográficos
Autores principales: Monsivais, Diana, Liao, Zian, Tang, Suni, Jiang, Peixin, Geng, Ting, Cope, Dominique, Dunn, Timothy, Guner, Joie, Radilla, Linda Alpuing, Guan, Xiaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659538/
https://www.ncbi.nlm.nih.gov/pubmed/37986901
http://dx.doi.org/10.21203/rs.3.rs-3471243/v1
Descripción
Sumario:Endometriosis is linked to increased infertility and pregnancy complications due to defective endometrial decidualization. We hypothesized that identification of altered signaling pathways during decidualization could identify the underlying cause of infertility and pregnancy complications. Our study reveals that transforming growth factor β (TGFβ) pathways are impaired in the endometrium of individuals with endometriosis, leading to defective decidualization. Through detailed transcriptomic analyses, we discovered abnormalities in TGFβ signaling pathways and key regulators, such as SMAD4, in the endometrium of affected individuals. We also observed compromised activity of bone morphogenetic proteins (BMP), a subset of the TGFβ family, that control endometrial receptivity. Using 3-dimensional models of endometrial stromal and epithelial assembloids, we showed that exogenous BMP2 improved decidual marker expression in individuals with endometriosis. Our findings unveil a previously unidentified dysfunction in BMP/SMAD signaling in the endometrium of individuals with endometriosis, explaining decidualization defects and subsequent pregnancy complications in these individuals.