Using Embryo Organoids to Discover Human-specific Mechanisms of Preimplantation Embryo Development and Early Pregnancy (EMBRYOx)
Using Embryo Organoids (i.e. Embryoids) to Discover Human-specific Mechanisms of Preimplantation Embryo Development and Early Pregnancy
Study Overview
Detailed Description
Study objectives:
Our primary objective is to compare the transcriptomic profiles of embryoids with those obtained from human embryos donated to research and cultured in two different oxygen conditions (monophasic oxygen strategy: 5% of O2 for 5 days vs. biphasic oxygen strategy: 5% of O2 for 3 days and 2% of O2 afterwards for 2 days). The transcriptomic profiles of human embryos donated to research and cultured in two different oxygen conditions were obtained in our previous study (PMID: 34789773). The biphasic oxygen strategy turned out to be beneficial for early embryo development and pregnancy. The comparison of transcriptomic profiles could allow us to validate the embryoids as a model in the study of preimplantation embryo development in vitro. Moreover, this could permit us to better understand the molecular mechanisms associated with the positive impact of the biphasic oxygen conditions on embryo development.
Our secondary objective is to identify new non-invasive biomarkers predictive for preimplantation embryo development and pregnancy.
This is a prospective, monocentric, observational study.
Study population:
Patients having first trimester voluntary termination of pregnancy in Montpellier University Hospital which have previously signed an informed consent. Placental tissues are collected after aspiration of abortion products. At least 5 organoids populations from 5 different placentas will be generated.
Material and methods:
- Collection of placental tissues after first trimester voluntary termination of pregnancy. Foetal tissues will not be collected as organoids are formed exclusively of trophoblast placental stem cells.
- Isolation of trophoblast placental stem cells.
- Culture, differentiation, and formation of embryoids.
- Culture of embryoids under monophasic (5% of O2 for 5 days) or biphasic oxygen conditions (5% of O2 for 3 days and 2% of O2 after for 2 days).
- ARN extraction (MiniKit Qiagen) and establishment of transcriptomic profiles (MGX-Montpellier GenomiX platform).
- Comparison of the transcriptomic profiles obtained with those of human embryos (Ingenuity Pathway Analysis).
- Cryopreservation of extra organoids in liquid nitrogen.
Assessment criteria:
Embryoids' dimension (100-150 um), proliferation/apoptosis index, expression of trophoblast markers (GATA3, KRT7, EGFR, TFAP2A, TFAP2C) by qPCR (Affymetrix Clariom) or immunohistochemistry.
Results and perspectives:
The investigators are expecting to obtain higher expression of proliferation, cellular survivor and pluripotency genes in embryoids cultured in biphasic oxygen conditions. If the investigators find the same outcomes after transcriptomic analysis of trophoblast organoids as those of human embryos, this would support the utilisation of organoids as a model in the study of human preimplantation embryo development.
Subsequently, the investigators could test the impact of other factors on the organoids' development (as culture medium composition, pH, etc.) and optimise the predictive value of non-invasive biomarkers (cf-DNA, PROK1 etc.).
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Sophie BROUILLET, MCU-PH
- Phone Number: 33 .4.67.33.59.54
- Email: s-brouillet@chu-montpellier.fr
Study Contact Backup
- Name: Fatima BARRY, AHU
- Phone Number: 33 4.67.33.64.04
- Email: fatima.barry@chu-montpellier.fr
Study Locations
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Montpellier, France, 34295
- Recruiting
- Uhmontpellier
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Contact:
- Sophie BROUILLET, MD
- Phone Number: 33 4.67.33.59.54
- Email: s-brouillet@chu-montpellier.fr
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Contact:
- Fatima BARRY, AHU
- Phone Number: 33 .4.67.33.64.04
- Email: fatima.barry@chu-montpellier.fr
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion criteria:
- No smoking patients without drug consumption or previous medication who are having first trimester voluntary termination of pregnancy surgically or medically induced.
Exclusion criteria:
- Patients smoking, drug consumption, previous medication
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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Single-group study
Patients having first trimester voluntary termination of pregnancy in Montpellier university hospital.
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Placental tissues are collected after aspiration of abortion products.
They are treated immediately in order to isolate placental stem cells.
Organoid culture is established and the obtained embryoids are cultured in monophasic or biphasic oxygen conditions.
Extra organoids are cryopreserved in liquid nitrogen
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Rate of research in preimplantation embryo development in vitro
Time Frame: 1 day
|
Establish and validate the use of embryoids from trophoblast placental stem cells as a 3D model for research in preimplantation embryo development in vitro.Our primary objective is to compare the transcriptomic profiles of embryoids with those obtained from human embryos donated to research and cultured in two different oxygen conditions (monophasic oxygen strategy: 5% of O2 for 5 days vs. biphasic oxygen strategy: 5% of O2 for 3 days and 2% of O2 afterwards for 2 days).
The transcriptomic profiles of human embryos donated to research and cultured in two different oxygen conditions were obtained in our previous study (PMID: 34789773).
The biphasic oxygen strategy turned out to be beneficial for early embryo development and pregnancy.
|
1 day
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Rate of Identification of new non-invasive biomarkers
Time Frame: 1 day
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Identification of new non-invasive biomarkers which are predictive for preimplantation embryo development and pregnancy
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1 day
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Samir HAMAMAH, PUPH, University Hospital, Montpellier
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RECHMPL22_0069
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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