Autophagy/Apoptosis Balance in Placental Vascular Pathologies (GROSSAUTOP-2)

Study of the Autophagy/Apoptosis Balance in Placental Vascular Pathologies

Pregnancy increases the risk of thrombosis. Placenta-mediated diseases are a risk factor for cardiovascular pathologies and can lead to maternal-fetal morbidity and mortality. It is essential to understand the cellular and molecular mechanisms of dysfunctions at the vascular-placental interface so that systemic vascular risk can be characterized and, ultimately, screened for, on the basis of new markers (targeted preventive management).

Deregulated autophagy could be the starting point for cell death by apoptosis or necrosis leading to complications.

The pathophysiological mechanisms involved in trophoblast apoptosis are incompletely described. This project follows on from the GrossAuTop-1 study, which investigated the intra- and inter-individual variability of autophagy and apoptosis activities in women during pregnancy. The aim of this project is to study autophagy and apoptosis activities specifically in women developing a placental vascular complication during pregnancy.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy Complications; Pre-Eclampsia; Growth Retardation, Intrauterine
• Intervention / Treatment: Diagnostic test: Blood test; Diagnostic test: Urine test

Detailed Description

Pregnancy increases the risk of thrombosis. Diseases mediated by the placenta are a risk factor for cardiovascular pathologies. They are responsible for significant maternal-fetal morbidity and mortality. Understanding and exploring the cellular and molecular mechanisms of dysfunctions at the vascular-placental interface could provide arguments for understanding systemic vascular risk, characterizing it and ultimately screening for it on the basis of new markers, thus paving the way for targeted preventive management, feeding into the general principle of precision medicine.

Autophagy enables cell development, differentiation and survival, but if deregulated, it could be the starting point for cell death by apoptosis or necrosis, and promote the development of complications.

The pathophysiological mechanisms involved in trophoblast apoptosis are incompletely described. A deregulation of the trophoblast proliferation/cell death balance could be at the origin of placental pathologies. The regulation of autophagy and autophagy-dependent events during pregnancy have not been fully identified.

We hypothesize that there is an intratrophoblastic dialogue between autophagy and apoptosis mechanisms, with the promotion of one partially inhibiting the other. The increase in trophoblastic autophagy during pregnancy could thus constitute an anti-apoptosis defense phenomenon, whose depletion would lead to cellular apoptosis and pathogenic consequences when it devastates the syncytiotrophoblast.

This project follows on from the GrossAuTop-1 study, which investigated the intra- and inter-individual variability of autophagy and apoptosis activities in women during pregnancy: the inclusions corresponded to all-pregnant women, the majority of whom developed a normal pregnancy. The aim of this project is to study autophagy and apoptosis activities specifically in women developing a placental vascular complication during pregnancy.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Anissa MEGZARI; Phone Number: +334 66 68 42 36; Email: drc@chu-nimes.fr
• Study Contact Backup: Name: Sylvie BOUVIER, Dr.; Phone Number: +334.66.68.32.11; Email: sylvie.bouvier@chu-nimes.fr

Study Locations

• France
  • Nîmes, France
    • Recruiting
    • Nimes University Hospital
    • Contact: sylvie bouvier; Phone Number: 0466686868; Email: sylvie.bouvier@chu-nimes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

An initial analysis of the data will make it possible to describe the population.

Quantitative variables will be expressed as mean and standard deviation, or median and quartiles. Qualitative variables will be expressed in headcount and percentage.

Description

Inclusion Criteria:

• Pregnant women developing a placental vascular complication (preeclampsia and/or intrauterine growth retardation), hospitalized and delivering at Nimes University Hospital.
• Pregnant woman with free and informed consent.
• Pregnant woman affiliated with and/or benefiting from a health insurance scheme.

Exclusion criteria:

• Multiple pregnancy.
• Presence of hypertension and/or proteinuria prior to pregnancy.
• Participant in an interventional drug study.
• Persons in a period of exclusion determined by another study.
• Persons under court protection, guardianship or curatorship.
• Persons unable to give consent.
• Persons for whom it is impossible to give informed information.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Pregnant women developing placental vascular complications; Pregnant adult women developing placental vascular complications such as preeclampsia and/or intrauterine growth retardation, hospitalized and delivering at Nimes University Hospital.

Diagnostic test: Blood test; 16 blood samples (16 tubes, i.e. 55.3 ml) will be taken at inclusion. Pregnant women will be seen every month as part of their pregnancy follow-up, and blood (11 tubes, i.e. 35.5 ml) and urine samples will be taken at each follow-up visit. At delivery, a systematic blood sample will be taken as part of the usual care, and an additional 11 tubes of blood (35.5 ml) will be taken.; Diagnostic test: Urine test; Urine samples will be taken at the inclusion visit and at each follow-up visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Baseline
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Month 1
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Month 2
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Month 3
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Month 4
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein	At delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apoptosis activity	Percentage of cells expressing annexin-V in pregnant women developing placental vascular pathology	Baseline
A. Apoptosis activity	Percentage of cells expressing annexin-V in pregnant women developing placental vascular pathology	Month 1
A. Apoptosis activity	Percentage of cells expressing annexin-V in pregnant women developing placental vascular pathology	Month 2
A. Apoptosis activity	Percentage of cells expressing annexin-V in pregnant women developing placental vascular pathology	Month 3
A. Apoptosis activity	Percentage of cells expressing annexin-V in pregnant women developing placental vascular pathology	Month 4
A. Apoptosis activity	Percentage of cells expressing annexin-V in pregnant women developing placental vascular pathology	At delivery
B. Autophagy/apoptosis balance	Ratio between percentage of cells expressing LC3 protein and percentage of cells expressing annexin-V	Baseline
B. Autophagy/apoptosis balance	Ratio between percentage of cells expressing LC3 protein and percentage of cells expressing annexin-V	Month 1
B. Autophagy/apoptosis balance	Ratio between percentage of cells expressing LC3 protein and percentage of cells expressing annexin-V	Month 2
B. Autophagy/apoptosis balance	Ratio between percentage of cells expressing LC3 protein and percentage of cells expressing annexin-V	Month 3
B. Autophagy/apoptosis balance	Ratio between percentage of cells expressing LC3 protein and percentage of cells expressing annexin-V	Month 4
B. Autophagy/apoptosis balance	Ratio between percentage of cells expressing LC3 protein and percentage of cells expressing annexin-V	At delivery
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein	LC3 protein will be measured as a %	Baseline
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein	LC3 protein will be measured as a %	Month 1
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein	LC3 protein will be measured as a %	Month 2
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein	LC3 protein will be measured as a %	Month 3
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein	LC3 protein will be measured as a %	Month 4
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein	LC3 protein will be measured as a %	At delivery
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V	Cells expressing annexin-V will be measured as a %	Baseline
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V	Cells expressing annexin-V will be measured as a %	Month 1
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V	Cells expressing annexin-V will be measured as a %	Month 2
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V	Cells expressing annexin-V will be measured as a %	Month 3
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V	Cells expressing annexin-V will be measured as a %	Month 4
C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V	Cells expressing annexin-V will be measured as a %	At delivery
D. Concentration of circulating Placental Growth Factor	Circulating Placental Growth Factor measured on blood samples in pg/mL	Baseline
D. Concentration of circulating Placental Growth Factor	Circulating Placental Growth Factor measured on blood samples in pg/mL	Month 1
D. Concentration of circulating Placental Growth Factor	Circulating Placental Growth Factor measured on blood samples in pg/mL	Month 2
D. Concentration of circulating Placental Growth Factor	Circulating Placental Growth Factor measured on blood samples in pg/mL	Month 3
D. Concentration of circulating Placental Growth Factor	Circulating Placental Growth Factor measured on blood samples in pg/mL	Month 4
D. Concentration of circulating Placental Growth Factor	Circulating Placental Growth Factor measured on blood samples in pg/mL	At delivery
D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1	Circulating soluble fms-like tyrosine kinase receptor-1 measured on blood samples in pg/mL	Baseline
D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1	Circulating soluble fms-like tyrosine kinase receptor-1 measured on blood samples in pg/mL	Month 1
D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1	Circulating soluble fms-like tyrosine kinase receptor-1 measured on blood samples in pg/mL	Month 2
D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1	Circulating soluble fms-like tyrosine kinase receptor-1 measured on blood samples in pg/mL	Month 3
D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1	Circulating soluble fms-like tyrosine kinase receptor-1 measured on blood samples in pg/mL	Month 4
D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1	Circulating soluble fms-like tyrosine kinase receptor-1 measured on blood samples in pg/mL	At delivery
E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria	Proteinuria will be measured in mg/L	Baseline
E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria	Proteinuria will be measured in mg/L	Month 1
E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria	Proteinuria will be measured in mg/L	Month 2
E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria	Proteinuria will be measured in mg/L	Month 3
E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria	Proteinuria will be measured in mg/L	Month 4
E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria	Proteinuria will be measured in mg/L	At delivery
E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria	Creatinuria will be measured in mmol/L	Baseline
E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria	Creatinuria will be measured in mmol/L	Month 1
E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria	Creatinuria will be measured in mmol/L	Month 2
E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria	Creatinuria will be measured in mmol/L	Month 3
E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria	Creatinuria will be measured in mmol/L	Month 4
E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria	Creatinuria will be measured in mmol/L	At delivery
E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein	C-reactive protein will be measured in mg/L	Baseline
E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein	C-reactive protein will be measured in mg/L	Month 1
E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein	C-reactive protein will be measured in mg/L	Month 2
E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein	C-reactive protein will be measured in mg/L	Month 3
E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein	C-reactive protein will be measured in mg/L	Month 4
E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein	C-reactive protein will be measured in mg/L	At delivery
E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen	Fibrinogen will be measured in g/L	Baseline
E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen	Fibrinogen will be measured in g/L	Month 1
E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen	Fibrinogen will be measured in g/L	Month 2
E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen	Fibrinogen will be measured in g/L	Month 3
E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen	Fibrinogen will be measured in g/L	Month 4
E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen	Fibrinogen will be measured in g/L	At delivery
E. Coagulation parameters : activated partial thromboplastin time	Activated partial thromboplastin time will be measured in seconds	Baseline
E. Coagulation parameters : activated partial thromboplastin time	Activated partial thromboplastin time will be measured in seconds	Month 1
E. Coagulation parameters : activated partial thromboplastin time	Activated partial thromboplastin time will be measured in seconds	Month 2
E. Coagulation parameters : activated partial thromboplastin time	Activated partial thromboplastin time will be measured in seconds	Month 3
E. Coagulation parameters : activated partial thromboplastin time	Activated partial thromboplastin time will be measured in seconds	Month 4
E. Coagulation parameters : activated partial thromboplastin time	Activated partial thromboplastin time will be measured in seconds	At delivery
E. Coagulation parameters : Prothrombin time	Prothrombin time will be measured in seconds	Baseline
E. Coagulation parameters : Prothrombin time	Prothrombin time will be measured in seconds	Month 1
E. Coagulation parameters : Prothrombin time	Prothrombin time will be measured in seconds	Month 2
E. Coagulation parameters : Prothrombin time	Prothrombin time will be measured in seconds	Month 3
E. Coagulation parameters : Prothrombin time	Prothrombin time will be measured in seconds	Month 4
E. Coagulation parameters : Prothrombin time	Prothrombin time will be measured in seconds	At delivery
E. Coagulation parameters : Fibrinogen	Fibrinogen will be measured in g/L	Baseline
E. Coagulation parameters : Fibrinogen	Fibrinogen will be measured in g/L	Month 1
E. Coagulation parameters : Fibrinogen	Fibrinogen will be measured in g/L	Month 2
E. Coagulation parameters : Fibrinogen	Fibrinogen will be measured in g/L	Month 3
E. Coagulation parameters : Fibrinogen	Fibrinogen will be measured in g/L	Month 4
E. Coagulation parameters : Fibrinogen	Fibrinogen will be measured in g/L	At delivery
E. Coagulation parameters : D-dimers	D-dimers will be measured in ng/mL	Baseline
E. Coagulation parameters : D-dimers	D-dimers will be measured in ng/mL	Month 1
E. Coagulation parameters : D-dimers	D-dimers will be measured in ng/mL	Month 2
E. Coagulation parameters : D-dimers	D-dimers will be measured in ng/mL	Month 3
E. Coagulation parameters : D-dimers	D-dimers will be measured in ng/mL	Month 4
E. Coagulation parameters : D-dimers	D-dimers will be measured in ng/mL	At delivery
E. Coagulation parameters : Fibrin monomers	Fibrin monomers will be measured in mg/mL	Baseline
E. Coagulation parameters : Fibrin monomers	Fibrin monomers will be measured in mg/mL	Month 1
E. Coagulation parameters : Fibrin monomers	Fibrin monomers will be measured in mg/mL	Month 2
E. Coagulation parameters : Fibrin monomers	Fibrin monomers will be measured in mg/mL	Month 3
E. Coagulation parameters : Fibrin monomers	Fibrin monomers will be measured in mg/mL	Month 4
E. Coagulation parameters : Fibrin monomers	Fibrin monomers will be measured in mg/mL	At delivery
E. Coagulation parameters : Thrombin generation time	Thrombin generation time will be measured in seconds	Baseline
E. Coagulation parameters : Thrombin generation time	Thrombin generation time will be measured in seconds	Month 1
E. Coagulation parameters : Thrombin generation time	Thrombin generation time will be measured in seconds	Month 2
E. Coagulation parameters : Thrombin generation time	Thrombin generation time will be measured in seconds	Month 3
E. Coagulation parameters : Thrombin generation time	Thrombin generation time will be measured in seconds	Month 4
E. Coagulation parameters : Thrombin generation time	Thrombin generation time will be measured in seconds	At delivery
Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils	White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils will be measured in 10^9/L	Baseline
Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils	White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils will be measured in 10^9/L	Month 1
Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils	White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils will be measured in 10^9/L	Month 2
Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils	White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils will be measured in 10^9/L	Month 3
Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils	White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils will be measured in 10^9/L	Month 4
Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils	White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils will be measured in 10^9/L	At delivery
Complete Blood Count : Red blood cells	Red blood cells will be measured in 10^12/L	Baseline
Complete Blood Count : Red blood cells	Red blood cells will be measured in 10^12/L	Month 1
Complete Blood Count : Red blood cells	Red blood cells will be measured in 10^12/L	Month 2
Complete Blood Count : Red blood cells	Red blood cells will be measured in 10^12/L	Month 3
Complete Blood Count : Red blood cells	Red blood cells will be measured in 10^12/L	Month 4
Complete Blood Count : Red blood cells	Red blood cells will be measured in 10^12/L	At delivery
Complete Blood Count : Hemoglobin	Hemoglobin will be measured in g/L	Baseline
Complete Blood Count : Hemoglobin	Hemoglobin will be measured in g/L	Month 1
Complete Blood Count : Hemoglobin	Hemoglobin will be measured in g/L	Month 2
Complete Blood Count : Hemoglobin	Hemoglobin will be measured in g/L	Month 3
Complete Blood Count : Hemoglobin	Hemoglobin will be measured in g/L	Month 4
Complete Blood Count : Hemoglobin	Hemoglobin will be measured in g/L	At delivery
Complete Blood Count : Platelets	Platelets will be measured in %	Baseline
Complete Blood Count : Platelets	Platelets will be measured in %	Month 1
Complete Blood Count : Platelets	Platelets will be measured in %	Month 2
Complete Blood Count : Platelets	Platelets will be measured in %	Month 3
Complete Blood Count : Platelets	Platelets will be measured in %	Month 4
Complete Blood Count : Platelets	Platelets will be measured in %	At delivery
Complete Blood Count : Hematocrit	Hematocrit will be measured in %	Baseline
Complete Blood Count : Hematocrit	Hematocrit will be measured in %	Month 1
Complete Blood Count : Hematocrit	Hematocrit will be measured in %	Month 2
Complete Blood Count : Hematocrit	Hematocrit will be measured in %	Month 3
Complete Blood Count : Hematocrit	Hematocrit will be measured in %	Month 4
Complete Blood Count : Hematocrit	Hematocrit will be measured in %	At delivery
Complete Blood Count : Mean Corpuscular Volume	Mean Corpuscular Volume will be measured in f/L	Baseline
Complete Blood Count : Mean Corpuscular Volume	Mean Corpuscular Volume will be measured in f/L	Month 1
Complete Blood Count : Mean Corpuscular Volume	Mean Corpuscular Volume will be measured in f/L	Month 2
Complete Blood Count : Mean Corpuscular Volume	Mean Corpuscular Volume will be measured in f/L	Month 3
Complete Blood Count : Mean Corpuscular Volume	Mean Corpuscular Volume will be measured in f/L	Month 4
Complete Blood Count : Mean Corpuscular Volume	Mean Corpuscular Volume will be measured in f/L	At delivery
Complete Blood Count : Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin will be measured in pg	Baseline
Complete Blood Count : Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin will be measured in pg	Month 1
Complete Blood Count : Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin will be measured in pg	Month 2
Complete Blood Count : Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin will be measured in pg	Month 3
Complete Blood Count : Mean Corpuscular Hemoglobin	Mean Corpuscular Hemoglobin will be measured in pg	Month 4
Complete Blood Count : Mean Corpuscular Hemoglobin Concentration	Mean Corpuscular Hemoglobin Concentration will be measured in g/L	Baseline
Complete Blood Count : Mean Corpuscular Hemoglobin Concentration	Mean Corpuscular Hemoglobin Concentration will be measured in g/L	Month 1
Complete Blood Count : Mean Corpuscular Hemoglobin Concentration	Mean Corpuscular Hemoglobin Concentration will be measured in g/L	Month 2
Complete Blood Count : Mean Corpuscular Hemoglobin Concentration	Mean Corpuscular Hemoglobin Concentration will be measured in g/L	Month 3
Complete Blood Count : Mean Corpuscular Hemoglobin Concentration	Mean Corpuscular Hemoglobin Concentration will be measured in g/L	At delivery
Ferritin	Ferritin will be measured in ng/mL	Baseline
Ferritin	Ferritin will be measured in ng/mL	Month 1
Ferritin	Ferritin will be measured in ng/mL	Month 2
Ferritin	Ferritin will be measured in ng/mL	Month 3
Ferritin	Ferritin will be measured in ng/mL	Month 4
Ferritin	Ferritin will be measured in ng/mL	At delivery
F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia	Constitutive thrombophilia: presence of prothrombin or factor V Leiden gene mutation, protein S, C, antithrombin deficiency will be sought: YES/NO	Baseline
F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia	Constitutive thrombophilia: presence of prothrombin or factor V Leiden gene mutation, protein S, C, antithrombin deficiency will be sought: YES/NO	Month 1
F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia	Constitutive thrombophilia: presence of prothrombin or factor V Leiden gene mutation, protein S, C, antithrombin deficiency will be sought: YES/NO	Month 2
F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia	Constitutive thrombophilia: presence of prothrombin or factor V Leiden gene mutation, protein S, C, antithrombin deficiency will be sought: YES/NO	Month 3
F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia	Constitutive thrombophilia: presence of prothrombin or factor V Leiden gene mutation, protein S, C, antithrombin deficiency will be sought: YES/NO	Month 4
F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia	Constitutive thrombophilia: presence of prothrombin or factor V Leiden gene mutation, protein S, C, antithrombin deficiency will be sought: YES/NO	At delivery
F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia	Acquired thrombophilia: presence of anti-phospholipid antibodies (lupus anticoagulant and/or anti-b2-glycoprotein 1 and/or anti-cardiolipid) will be sought: YES/NO	Baseline
F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia	Acquired thrombophilia: presence of anti-phospholipid antibodies (lupus anticoagulant and/or anti-b2-glycoprotein1 and/or anti-cardiolipid) will be sought: YES/NO	Month 1
F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia	Acquired thrombophilia: presence of anti-phospholipid antibodies (lupus anticoagulant and/or anti-b2-glycoprotein1 and/or anti-cardiolipid) will be sought: YES/NO	Month 2
F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia	Acquired thrombophilia: presence of anti-phospholipid antibodies (lupus anticoagulant and/or anti-b2-glycoprotein 1 and/or anti-cardiolipid) will be sought: YES/NO	Month 3
F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia	Acquired thrombophilia: presence of anti-phospholipid antibodies (lupus anticoagulant and/or anti-b2-glycoprotein 1 and/or anti-cardiolipid) will be sought: YES/NO	Month 4
F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia	Acquired thrombophilia: presence of anti-phospholipid antibodies (lupus anticoagulant and/or anti-b2-glycoprotein 1 and/or anti-cardiolipid) will be sought: YES/NO	At delivery
Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance	The results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance) will be compared with data obtained from the first GrossAuTop-1 study (normal pregnancy).	Baseline
Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance	The results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance) will be compared with data obtained from the first GrossAuTop-1 study (normal pregnancy).	Month 1
Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance	The results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance) will be compared with data obtained from the first GrossAuTop-1 study (normal pregnancy).	Month 2
Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance	The results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance) will be compared with data obtained from the first GrossAuTop-1 study (normal pregnancy).	Month 3
Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance	The results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance) will be compared with data obtained from the first GrossAuTop-1 study (normal pregnancy).	Month 4
Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance	The results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance) will be compared with data obtained from the first GrossAuTop-1 study (normal pregnancy).	At delivery
H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.	Determination of fetal hemoglobin (HbF) in maternal blood, measured in %	Baseline
H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.	Determination of fetal hemoglobin (HbF) in maternal blood, measured in %	Month 1
H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.	Determination of fetal hemoglobin (HbF) in maternal blood, measured in %	Month 2
H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.	Determination of fetal hemoglobin (HbF) in maternal blood, measured in %	Month 3
H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.	Determination of fetal hemoglobin (HbF) in maternal blood, measured in %	Month 4
H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.	Determination of fetal hemoglobin (HbF) in maternal blood, measured in %	At delivery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
I. Constitution of a Biobank	A biobank (plasmabank, serum bank, mononuclear cells) will be set up for ancillary studies on other markers of placental vascular pathologies and venous thromboembolic disease.	Baseline

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Marie PORTES, Dr., Centre Hospitalier Universitaire de Nīmes; Principal Investigator: Mathieu FORTIER, Dr., Centre Hospitalier Universitaire de Nīmes; Principal Investigator: Jean-Christophe GRIS, Pr., Centre Hospitalier Universitaire de Nīmes; Principal Investigator: Eve MOUSTY, Dr., Centre Hospitalier Universitaire de Nīmes; Principal Investigator: Vincent LETOUZEY, Dr., Centre Hospitalier Universitaire de Nīmes; Principal Investigator: Stéphanie HUBERLANT, Dr., Centre Hospitalier Universitaire de Nīmes; Principal Investigator: Chloé BOURGUIGNON, Dr., Centre Hospitalier Universitaire de Nīmes

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 15, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pregnancy; placenta; apoptosis; autophagy; trophoblasts
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Fetal Diseases; Growth Disorders; Hypertension, Pregnancy-Induced; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Pre-Eclampsia; Fetal Growth Retardation; Pregnancy Complications; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Urological; Clinical Chemistry Tests; Hematologic Tests; Urinalysis
• Other Study ID Numbers: NIMAO/2024-1/SB01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No