Autophagy/Apoptosis Balance During Pregnancy

Study Overview
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Brief Summary
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The object of this study is to assess the intra- and inter-individual variability of apoptosis and autophagy activities in women during pregnancy: 1 / in women with a normal pregnancy and 2 / in pregnant women particularly at risk of complications. The study investigators hypothesize that there would be an intra-trophoblastic dialogue between the mechanisms of autophagy and apoptosis, the promotion of one partially inhibiting the other. The increase in trophoblastic autophagy during pregnancy could thus constitute an anti-apoptosis defense phenomenon, the exhaustion of which would lead to cellular apoptosis and to pathogenic consequences when it devastates the syncytiotrophoblast.

Official Title
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Autophagy/Apoptosis Balance During Pregnancy

Conditions
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Pregnancy Related

Intervention / Treatment
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* Other: Blood test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients followed at the CHU Nîmes prior to 33 weeks gestation who give birth at the hospital The patient must have given their free and informed consent and signed the consent form The patient must be a member or beneficiary of a health insurance plan Exclusion Criteria: The subject is participating in a category 1 interventional study associated with a medication, or is in a period of exclusion determined by a previous study The subject refuses to sign the consent It is impossible to give the subject informed information The patient is under safeguard of justice or state guardianship Multiple pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A<br>without medical history or risk factors, with a normal pregnancy | Other: Blood test<br>* Blood samples taken to test levels of autophagy and apoptosis<br>|
| Group B<br>without medical history or risk factors, developing a pregnancy complication | Other: Blood test<br>* Blood samples taken to test levels of autophagy and apoptosis<br>|
| Group C<br>with risk of complication, having a normal pregnancy | Other: Blood test<br>* Blood samples taken to test levels of autophagy and apoptosis<br>|
| Group D<br>with a risk of complication, developing a pregnancy complication | Other: Blood test<br>* Blood samples taken to test levels of autophagy and apoptosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Potential autophagy induction activity in all groups | Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Day 0 | 
| Potential autophagy induction activity in all groups | Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 1 | 
| Potential autophagy induction activity in all groups | Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 2 | 
| Potential autophagy induction activity in all groups | Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 3 | 
| Potential autophagy induction activity in all groups | Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 4 | 
| Potential autophagy induction activity in all groups | Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 5 | 
| Potential autophagy induction activity in all groups | Microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Delivery plus or minus 2 weeks (Month 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type of autophagy inhibition per patient in all groups | Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Day 0 | 
| Type of autophagy inhibition per patient in all groups | Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 1 | 
| Type of autophagy inhibition per patient in all groups | Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 2 | 
| Type of autophagy inhibition per patient in all groups | Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 3 | 
| Type of autophagy inhibition per patient in all groups | Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 4 | 
| Type of autophagy inhibition per patient in all groups | Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 5 | 
| Type of autophagy inhibition per patient in all groups | Early/late; measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Delivery plus or minus 2 weeks (Month 6) | 
| Potential apoptosis induction activity in all groups | % cells positive for Annexin V | Day 0 | 
| Potential apoptosis induction activity in all groups | % cells positive for Annexin V | Month 1 | 
| Potential apoptosis induction activity in all groups | % cells positive for Annexin V | Month 2 | 
| Potential apoptosis induction activity in all groups | % cells positive for Annexin V | Month 3 | 
| Potential apoptosis induction activity in all groups | % cells positive for Annexin V | Month 4 | 
| Potential apoptosis induction activity in all groups | % cells positive for Annexin V | Month 5 | 
| Potential apoptosis induction activity in all groups | % cells positive for Annexin V | Delivery plus or minus 2 weeks (Month 6) | 
| Inter- and intra-individual apoptosis/autophagy ratio in all groups |  | Day 0 | 
| Inter- and intra-individual apoptosis/autophagy ratio in all groups |  | Month 1 | 
| Inter- and intra-individual apoptosis/autophagy ratio in all groups |  | Month 2 | 
| Inter- and intra-individual apoptosis/autophagy ratio in all groups |  | Month 3 | 
| Inter- and intra-individual apoptosis/autophagy ratio in all groups |  | Month 4 | 
| Inter- and intra-individual apoptosis/autophagy ratio in all groups |  | Month 5 | 
| Inter- and intra-individual apoptosis/autophagy ratio in all groups |  | Delivery plus or minus 2 weeks (Month 6) | 
| Autophagy kinetics between groups | measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Day 0 | 
| Autophagy kinetics between groups | measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 1 | 
| Autophagy kinetics between groups | measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 2 | 
| Autophagy kinetics between groups | measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 3 | 
| Autophagy kinetics between groups | measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 4 | 
| Autophagy kinetics between groups | measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Month 5 | 
| Autophagy kinetics between groups | measured by microtubule-associated protein 1A/1B-light chain 3 fluorescence ratio | Delivery plus or minus 2 weeks (Month 6) | 
| Apoptosis kinetics between groups | measured by % cells positive for Annexin V | Day 0 | 
| Apoptosis kinetics between groups | measured by % cells positive for Annexin V | Month 1 | 
| Apoptosis kinetics between groups | measured by % cells positive for Annexin V | Month 2 | 
| Apoptosis kinetics between groups | measured by % cells positive for Annexin V | Month 3 | 
| Apoptosis kinetics between groups | measured by % cells positive for Annexin V | Month 4 | 
| Apoptosis kinetics between groups | measured by % cells positive for Annexin V | Month 5 | 
| Apoptosis kinetics between groups | measured by % cells positive for Annexin V | Delivery plus or minus 2 weeks (Month 6) | 
| Placental Growth Factor in each group | pg/ml measured by ELISA | Day 0 | 
| Placental Growth Factor in each group | pg/ml measured by ELISA | Month 1 | 
| Placental Growth Factor in each group | pg/ml measured by ELISA | Month 2 | 
| Placental Growth Factor in each group | pg/ml measured by ELISA | Month 3 | 
| Placental Growth Factor in each group | pg/ml measured by ELISA | Month 4 | 
| Placental Growth Factor in each group | pg/ml measured by ELISA | Month 5 | 
| Placental Growth Factor in each group | pg/ml measured by ELISA | Delivery plus or minus 2 weeks (Month 6) | 
| Soluble fms-like tyrosine kinase-1 | pg/ml measured by ELISA | Day 0 | 
| Soluble fms-like tyrosine kinase-1 | pg/ml measured by ELISA | Month 1 | 
| Soluble fms-like tyrosine kinase-1 | pg/ml measured by ELISA | Month 2 | 
| Soluble fms-like tyrosine kinase-1 | pg/ml measured by ELISA | Month 3 | 
| Soluble fms-like tyrosine kinase-1 | pg/ml measured by ELISA | Month 4 | 
| Soluble fms-like tyrosine kinase-1 | pg/ml measured by ELISA | Month 5 | 
| Soluble fms-like tyrosine kinase-1 | pg/ml measured by ELISA | Delivery plus or minus 2 weeks (Month 6) | 
| Constitutive thrombophilia | presence/absence of the prothrombin gene or factor V Leiden mutation, protein S, C or antithrombin deficiency | Day 0 | 
| Acquired thrombophilia | Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid). | Day 0 | 
| Acquired thrombophilia | Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid). | Month 1 | 
| Acquired thrombophilia | Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid). | Month 2 | 
| Acquired thrombophilia | Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid). | Month 3 | 
| Acquired thrombophilia | Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid). | Month 4 | 
| Acquired thrombophilia | Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid). | Month 5 | 
| Acquired thrombophilia | Presence/absence of anti-phospholipid antibodies (lupus anticoagulant and/or anti beta2-GP1 and/or anti-cardiolipid). | Delivery plus or minus 2 weeks (Month 6) | 
| Whole blood count |  | Day 0 | 
| Whole blood count |  | Month 1 | 
| Whole blood count |  | Month 2 | 
| Whole blood count |  | Month 3 | 
| Whole blood count |  | Month 4 | 
| Whole blood count |  | Month 5 | 
| Whole blood count |  | Delivery plus or minus 2 weeks (Month 6) | 
| Renal function | creatinemia, proteinuria / creatinuria ratio | Day 0 | 
| Renal function | creatinemia, proteinuria / creatinuria ratio | Month 1 | 
| Renal function | creatinemia, proteinuria / creatinuria ratio | Month 2 | 
| Renal function | creatinemia, proteinuria / creatinuria ratio | Month 3 | 
| Renal function | creatinemia, proteinuria / creatinuria ratio | Month 4 | 
| Renal function | creatinemia, proteinuria / creatinuria ratio | Month 5 | 
| Renal function | creatinemia, proteinuria / creatinuria ratio | Delivery plus or minus 2 weeks (Month 6) | 
| Fibrin levels | D dimers and fibrin monomers | Day 0 | 
| Fibrin levels | D dimers and fibrin monomers | Month 1 | 
| Fibrin levels | D dimers and fibrin monomers | Month 2 | 
| Fibrin levels | D dimers and fibrin monomers | Month 3 | 
| Fibrin levels | D dimers and fibrin monomers | Month 4 | 
| Fibrin levels | D dimers and fibrin monomers | Month 5 | 
| Fibrin levels | D dimers and fibrin monomers | Delivery plus or minus 2 weeks (Month 6) | 
| Inflammation | C-reactive protein level | Day 0 | 
| Inflammation | C-reactive protein level | Month 1 | 
| Inflammation | C-reactive protein level | Month 2 | 
| Inflammation | C-reactive protein level | Month 3 | 
| Inflammation | C-reactive protein level | Month 4 | 
| Inflammation | C-reactive protein level | Month 5 | 
| Inflammation | C-reactive protein level | Delivery plus or minus 2 weeks (Month 6) | 
| Activated partial thromboplastin time | seconds | Day 0 | 
| Activated partial thromboplastin time | seconds | Month 1 | 
| Activated partial thromboplastin time | seconds | Month 2 | 
| Activated partial thromboplastin time | seconds | Month 3 | 
| Activated partial thromboplastin time | seconds | Month 4 | 
| Activated partial thromboplastin time | seconds | Month 5 | 
| Activated partial thromboplastin time | seconds | Delivery plus or minus 2 weeks (Month 6) | 
| Prothrombin time | seconds | Day 0 | 
| Prothrombin time | seconds | Month 1 | 
| Prothrombin time | seconds | Month 2 | 
| Prothrombin time | seconds | Month 3 | 
| Prothrombin time | seconds | Month 4 | 
| Prothrombin time | seconds | Month 5 | 
| Prothrombin time | seconds | Delivery plus or minus 2 weeks (Month 6) | 
| Fibrinogen level | g/L | Day 0 | 
| Fibrinogen level | g/L | Month 1 | 
| Fibrinogen level | g/L | Month 2 | 
| Fibrinogen level | g/L | Month 3 | 
| Fibrinogen level | g/L | Month 4 | 
| Fibrinogen level | g/L | Month 5 | 
| Fibrinogen level | g/L | Delivery plus or minus 2 weeks (Month 6) | 
| Thrombin generation time | seconds | Month 1 | 
| Thrombin generation time | seconds | Month 2 | 
| Thrombin generation time | seconds | Month 3 | 
| Thrombin generation time | seconds | Month 4 | 
| Thrombin generation time | seconds | Month 5 | 
| Thrombin generation time | seconds | Delivery plus or minus 2 weeks (Month 6) | 
| Thrombin generation time | seconds | Day 0 | 
| fetal haemoglobin | g/L | Month 1 | 
| fetal haemoglobin | g/L | Month 2 | 
| fetal haemoglobin | g/L | Month 3 | 
| fetal haemoglobin | g/L | Month 4 | 
| fetal haemoglobin | g/L | Month 5 | 
| fetal haemoglobin | g/L | Delivery plus or minus 2 weeks (Month 6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autophagy, Apoptosis