NCT06779916

Autophagy/Apoptosis Balance in Placental Vascular Pathologies

Study of the Autophagy/Apoptosis Balance in Placental Vascular Pathologies

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 50 (estimated)
• Sponsor: Centre Hospitalier Universitaire de Nīmes · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Pregnancy Complications
• Pre-Eclampsia
• Growth Retardation, Intrauterine

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2025-05-02
• Primary completion: 2026-05-01
• Completion: 2027-05-01
• First posted: 2025-01-17
• Last updated: 2025-11-17

Locations

1 site across 1 country: France