Study of the Autophagy/Apoptosis Balance in Placental Vascular Pathologies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —(Adult, Older Adult)
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Blood test (Diagnostic Test)
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.
干预措施: Urine test (Diagnostic Test)
结局指标
主要结局
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
时间窗: At delivery
Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
时间窗: Baseline
Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
时间窗: Month 1
Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
时间窗: Month 2
Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
时间窗: Month 3
Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
Percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
时间窗: Month 4
Level of autophagy in trophoblastic test cells quantified by the percentage of cells expressing LC3 (microtubule-associated protein light chain 3) protein
次要结局
- Apoptosis activity(Baseline)
- A. Apoptosis activity(At delivery)
- B. Autophagy/apoptosis balance(At delivery)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein(At delivery)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V(At delivery)
- D. Concentration of circulating Placental Growth Factor(At delivery)
- D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1(At delivery)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria(At delivery)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria(At delivery)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein(At delivery)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen(At delivery)
- E. Coagulation parameters : activated partial thromboplastin time(At delivery)
- E. Coagulation parameters : Prothrombin time(At delivery)
- E. Coagulation parameters : Fibrinogen(At delivery)
- E. Coagulation parameters : D-dimers(At delivery)
- E. Coagulation parameters : Fibrin monomers(At delivery)
- Complete Blood Count : Hematocrit(At delivery)
- E. Coagulation parameters : Thrombin generation time(At delivery)
- Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils(At delivery)
- Complete Blood Count : Red blood cells(At delivery)
- Complete Blood Count : Hemoglobin(At delivery)
- Complete Blood Count : Platelets(At delivery)
- Complete Blood Count : Mean Corpuscular Hemoglobin(Month 4)
- Complete Blood Count : Mean Corpuscular Volume(At delivery)
- Complete Blood Count : Mean Corpuscular Hemoglobin Concentration(At delivery)
- Ferritin(At delivery)
- F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia(At delivery)
- F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia(At delivery)
- Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance(At delivery)
- H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.(At delivery)
- E. Coagulation parameters : Fibrinogen(Month 4)
- A. Apoptosis activity(Month 1)
- A. Apoptosis activity(Month 2)
- A. Apoptosis activity(Month 3)
- A. Apoptosis activity(Month 4)
- B. Autophagy/apoptosis balance(Baseline)
- B. Autophagy/apoptosis balance(Month 1)
- B. Autophagy/apoptosis balance(Month 2)
- B. Autophagy/apoptosis balance(Month 3)
- E. Coagulation parameters : Prothrombin time(Month 1)
- B. Autophagy/apoptosis balance(Month 4)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein(Baseline)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein(Month 1)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein(Month 2)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein(Month 3)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: LC3 protein(Month 4)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V(Baseline)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V(Month 1)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V(Month 2)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V(Month 3)
- C.Kinetics of different biological activities (autophagy, apoptosis, autophagy/apoptosis balance) during pregnancy follow-up: cells expressing annexin-V(Month 4)
- D. Concentration of circulating Placental Growth Factor(Baseline)
- D. Concentration of circulating Placental Growth Factor(Month 1)
- D. Concentration of circulating Placental Growth Factor(Month 2)
- D. Concentration of circulating Placental Growth Factor(Month 3)
- Ferritin(Month 2)
- D. Concentration of circulating Placental Growth Factor(Month 4)
- D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1(Baseline)
- D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1(Month 1)
- D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1(Month 2)
- D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1(Month 3)
- D. Concentration of circulating soluble fms-like tyrosine kinase receptor-1(Month 4)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria(Baseline)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria(Month 1)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria(Month 2)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria(Month 3)
- E. Coagulation parameters : D-dimers(Baseline)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: proteinuria(Month 4)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria(Baseline)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria(Month 1)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria(Month 2)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria(Month 3)
- E. Coagulation parameters : Prothrombin time(Month 2)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: creatinuria(Month 4)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein(Baseline)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein(Month 1)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein(Month 2)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein(Month 3)
- Ferritin(Month 1)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: C-reactive protein(Month 4)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen(Baseline)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen(Month 1)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen(Month 2)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen(Month 3)
- E. Correlation between autophagy/apoptosis balance and markers of renal function: Fibrinogen(Month 4)
- E. Coagulation parameters : activated partial thromboplastin time(Baseline)
- E. Coagulation parameters : activated partial thromboplastin time(Month 1)
- E. Coagulation parameters : activated partial thromboplastin time(Month 2)
- E. Coagulation parameters : activated partial thromboplastin time(Month 3)
- E. Coagulation parameters : activated partial thromboplastin time(Month 4)
- E. Coagulation parameters : Prothrombin time(Baseline)
- E. Coagulation parameters : Prothrombin time(Month 3)
- E. Coagulation parameters : Prothrombin time(Month 4)
- E. Coagulation parameters : Fibrinogen(Baseline)
- E. Coagulation parameters : Fibrinogen(Month 1)
- E. Coagulation parameters : Fibrinogen(Month 2)
- E. Coagulation parameters : Fibrinogen(Month 3)
- E. Coagulation parameters : D-dimers(Month 1)
- E. Coagulation parameters : D-dimers(Month 2)
- E. Coagulation parameters : D-dimers(Month 3)
- E. Coagulation parameters : D-dimers(Month 4)
- E. Coagulation parameters : Fibrin monomers(Baseline)
- E. Coagulation parameters : Fibrin monomers(Month 1)
- E. Coagulation parameters : Fibrin monomers(Month 2)
- E. Coagulation parameters : Fibrin monomers(Month 3)
- E. Coagulation parameters : Fibrin monomers(Month 4)
- E. Coagulation parameters : Thrombin generation time(Baseline)
- E. Coagulation parameters : Thrombin generation time(Month 1)
- E. Coagulation parameters : Thrombin generation time(Month 2)
- E. Coagulation parameters : Thrombin generation time(Month 3)
- E. Coagulation parameters : Thrombin generation time(Month 4)
- Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils(Baseline)
- Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils(Month 1)
- Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils(Month 2)
- Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils(Month 3)
- Complete Blood Count : White blood cells, Lymphocytes, Neutrophils, Monocytes, Eosinophils and Basophils(Month 4)
- Complete Blood Count : Red blood cells(Baseline)
- Complete Blood Count : Red blood cells(Month 1)
- Complete Blood Count : Red blood cells(Month 2)
- Complete Blood Count : Red blood cells(Month 3)
- Complete Blood Count : Red blood cells(Month 4)
- Complete Blood Count : Hemoglobin(Baseline)
- Complete Blood Count : Hemoglobin(Month 1)
- Complete Blood Count : Hemoglobin(Month 2)
- Complete Blood Count : Hemoglobin(Month 3)
- Complete Blood Count : Hemoglobin(Month 4)
- Complete Blood Count : Platelets(Baseline)
- Complete Blood Count : Platelets(Month 1)
- Complete Blood Count : Platelets(Month 2)
- Complete Blood Count : Platelets(Month 3)
- Complete Blood Count : Platelets(Month 4)
- Complete Blood Count : Hematocrit(Baseline)
- Complete Blood Count : Hematocrit(Month 1)
- Complete Blood Count : Hematocrit(Month 2)
- Complete Blood Count : Hematocrit(Month 3)
- Complete Blood Count : Hematocrit(Month 4)
- Complete Blood Count : Mean Corpuscular Volume(Baseline)
- Complete Blood Count : Mean Corpuscular Volume(Month 1)
- Complete Blood Count : Mean Corpuscular Volume(Month 2)
- Complete Blood Count : Mean Corpuscular Volume(Month 3)
- Complete Blood Count : Mean Corpuscular Volume(Month 4)
- Complete Blood Count : Mean Corpuscular Hemoglobin(Baseline)
- Complete Blood Count : Mean Corpuscular Hemoglobin(Month 1)
- Complete Blood Count : Mean Corpuscular Hemoglobin(Month 2)
- Complete Blood Count : Mean Corpuscular Hemoglobin(Month 3)
- Complete Blood Count : Mean Corpuscular Hemoglobin Concentration(Baseline)
- Complete Blood Count : Mean Corpuscular Hemoglobin Concentration(Month 1)
- Complete Blood Count : Mean Corpuscular Hemoglobin Concentration(Month 2)
- Complete Blood Count : Mean Corpuscular Hemoglobin Concentration(Month 3)
- Ferritin(Baseline)
- Ferritin(Month 3)
- Ferritin(Month 4)
- F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia(Baseline)
- F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia(Month 1)
- F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia(Month 2)
- F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia(Month 3)
- F. Association between autophagy/apoptosis balance and the presence of constitutive thrombophilia(Month 4)
- F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia(Baseline)
- F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia(Month 1)
- F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia(Month 2)
- F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia(Month 3)
- F. Association between autophagy/apoptosis balance and the presence of acquired thrombophilia(Month 4)
- Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance(Baseline)
- Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance(Month 1)
- Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance(Month 2)
- Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance(Month 3)
- Comparison of results on trophoblastic cell autophagy induction potential, apoptosis and autophagy/apoptosis balance(Month 4)
- H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.(Baseline)
- H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.(Month 1)
- H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.(Month 2)
- H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.(Month 3)
- H.Association between autophagy/apoptosis balance and HbF levels in maternal blood during pregnancy.(Month 4)
