1. Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.
- Author
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Liao Z, Tang S, Jiang P, Geng T, Cope DI, Dunn TN, Guner J, Radilla LA, Guan X, and Monsivais D
- Subjects
- Pregnancy, Female, Humans, Decidua metabolism, Bone Morphogenetic Proteins genetics, Bone Morphogenetic Proteins metabolism, Transforming Growth Factor beta metabolism, Signal Transduction, Endometriosis genetics, Endometriosis metabolism, Infertility metabolism, Pregnancy Complications metabolism
- Abstract
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 reveal dysfunction of BMP/SMAD signaling in the endometrium of individuals with endometriosis, explaining decidualization defects and subsequent pregnancy complications in these individuals., (© 2024. The Author(s).)
- Published
- 2024
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