Explore the Role of NLRP7 in the Regulation of Progestereone Induced Decidualization of Human Endometrial Stroma Cells

October 3, 2022 updated by: National Cheng-Kung University Hospital

Dr. Pao-Lin Kuo (Department of Obstetrics and Gynecology)

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.

Study Overview

Status

Completed

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.

Study Type

Observational

Enrollment (Actual)

204

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Tainan, Taiwan, 70428
        • National Cheng-Kung University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

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.

Description

Inclusion Criteria:

Fertility woman 20-50 years-of-age -Hydatidiform Mole or Habitualabortion Exclusion Criteria:NA

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NLRP7 expressed in the decidualized stromal cells of the human endometrium during the first trimester.
Time Frame: 1 day
The tissue sections of the non-pregnant endometrium (n = 5) or the first trimester endometrium (n = 5) were deparaffinized, rehydrated and stained with NLRP7 antibody. Representative images of NLRP7 immunohistochemistry in the endometrium are shown. The NLRP7 signal was developed with the anti-rabbit HRP antibody and AEC substrate. Staining with the 2nd antibody only served as the negative control. Arrows point to the endometrial stromal cells. NLRP7 dominantly appeared in the swollen decidualized stromal cells of pregnant endometrium, but not in the stromal cells of non-pregnant endometrium (magnification 200X)
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 1, 2015

Primary Completion (ACTUAL)

July 1, 2018

Study Completion (ACTUAL)

July 1, 2018

Study Registration Dates

First Submitted

October 28, 2019

First Submitted That Met QC Criteria

October 30, 2019

First Posted (ACTUAL)

November 1, 2019

Study Record Updates

Last Update Posted (ACTUAL)

October 5, 2022

Last Update Submitted That Met QC Criteria

October 3, 2022

Last Verified

November 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • A-ER-102-440

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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