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

Centre Hospitalier Universitaire de Nīmes

Status: Enrolling

Conditions: Growth Retardation, Intrauterine; Pre-Eclampsia; Pregnancy Complications

Treatments: Diagnostic Test: Blood test; Diagnostic Test: Urine test

Study type: Observational

Funder types: Other

Identifiers

NCT06779916

NIMAO/2024-1/SB01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

50 participants in 1 patient group

Pregnant women developing placental vascular complications

Description:

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

Treatment:

Diagnostic Test: Urine test

Diagnostic Test: Blood test