Explore the Role of NLRP7 in the Regulation of Progestereone Induced Decidualization of Human Endometrial Stroma Cells
Condition: Inflammatory Response; Abortion, Habitual
MeSH terms: Abortion, Habitual
Study type: Observational

Summary: 
      The investigators have found that NLRP7 was upregulated and nuclear translocated in an in
      vitro model of decidualization. Knock-down or overexpression of NLRP7 reduced or enhanced the
      expression of decidual marker IGFBP-1. NLRP7 was also found to promote progesterone receptor
      (PR) activity. So, the investigators hypothesized that NLRP7 may regulate
      progesterone-induced decidualization of human endometrial stromal cells. Part I is to explore
      how NLRP7 is induced during the decidualization. According to the luciferase activities of
      NLRP7 promoter luciferase reporter systems, the region from -100 to +37 or from -1200 to -100
      had positive or negative regulatory elements, respectively, in the in vitro decidualization.
      Part II is to explore how NLRP7 contributes the decidualization of endometrial stromal cells.
      By immunoprecipitations of NLRP7 or PR, the investigators found NLRP7 might involve in the
      transcriptional complex of PR in the in vitro decidualization. The NLRP7 interacting protein
      in the co-immunoprecipitations the investigatorsre analyzed by LC/MS-MS. Part III is to
      explore the effects of NLRP7 mutations on in vitro decidualization and macrophage
      differentiation.

      Comparing to RFP control, the investigators found wild-type NLRP7 enhanced but NLRP7 mutants
      reduced IGFBP-1 expression in the in vitro decidualization. In the M1 macrophage
      differentiation of THP-1, wild-type and mutant NLRP7 reduced IL-1β expression compared to the
      RFP control. Part IV is to explore a role of MPA in macrophage differentiation. MPA drives
      THP-1 cells a M2-like macrophage differentiation toward a phenotype of decidual macrophages,
      which promoted in vitro decidualization and trophoblastic invasion, but tolerated TLR ligands
      stimulations. In conclusion, NLRP7 contributes in vitro decidualization of endometrial
      stromal cells; NLRP7 mutation may impede in vitro decidualization; NLRP7 may suppress IL-1
      expression in M1 macrophage differentiation; MPA drives M2 macrophage differentiation toward
      a phenotype of decidual macrophage.
    

Detailed description: 
      The investigators have found that NLRP7 was upregulated and nuclear translocated in an in
      vitro model of decidualization. Knock-down or overexpression of NLRP7 reduced or enhanced the
      expression of decidual marker IGFBP-1. NLRP7 was also found to promote progesterone receptor
      (PR) activity. So, the investigators hypothesized that NLRP7 may regulate
      progesterone-induced decidualization of human endometrial stromal cells. Part I is to explore
      how NLRP7 is induced during the decidualization. According to the luciferase activities of
      NLRP7 promoter luciferase reporter systems, the region from -100 to +37 or from -1200 to -100
      had positive or negative regulatory elements, respectively, in the in vitro decidualization.
      Part II is to explore how NLRP7 contributes the decidualization of endometrial stromal cells.
      By immunoprecipitations of NLRP7 or PR, the investigators found NLRP7 might involve in the
      transcriptional complex of PR in the in vitro decidualization. The NLRP7 interacting protein
      in the co-immunoprecipitations the investigatorsre analyzed by LC/MS-MS. Part III is to
      explore the effects of NLRP7 mutations on in vitro decidualization and macrophage
      differentiation. Comparing to RFP control, the investigators found wild-type NLRP7 enhanced
      but NLRP7 mutants reduced IGFBP-1 expression in the in vitro decidualization. In the M1
      macrophage differentiation of THP-1, wild-type and mutant NLRP7 reduced IL-1β expression
      compared to the RFP control. Part IV is to explore a role of MPA in macrophage
      differentiation. MPA drives THP-1 cells a M2-like macrophage differentiation toward a
      phenotype of decidual macrophages, which promoted in vitro decidualization and trophoblastic
      invasion, but tolerated TLR ligands stimulations. In conclusion, NLRP7 contributes in vitro
      decidualization of endometrial stromal cells; NLRP7 mutation may impede in vitro
      decidualization; NLRP7 may suppress IL-1 expression in M1 macrophage differentiation; MPA
      drives M2 macrophage differentiation toward a phenotype of decidual macrophage.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        It is known that NLRP7, a member of the protein family related to innate immunity, is
        associated with habitual abortion, and it is found that dysfunction of NLRP7 protein may
        affect endometrial decidualization and facilitate embryo implantation.
      
Biospecimen description: 
      Blood