Exploring the Importance of Differential Expression of Autophagy Markers in Term Placentas from Late-Onset Preeclamptic Pregnancies

Author:

Garcia-Puente Luis M.12,García-Montero Cielo12ORCID,Fraile-Martinez Oscar12ORCID,Bujan Julia12ORCID,De León-Luis Juan A.345ORCID,Bravo Coral345,Rodríguez-Benitez Patrocinio356ORCID,López-González Laura27,Díaz-Pedrero Raul27ORCID,Álvarez-Mon Melchor128,García-Honduvilla Natalio12ORCID,Saez Miguel A.129ORCID,Ortega Miguel A.12ORCID

Affiliation:

1. Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain

2. Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain

3. Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain

4. Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain

5. Health Research Institute Gregorio Marañón, 28009 Madrid, Spain

6. Department of Nephrology, University Hospital Gregorio Marañón, 28009 Madrid, Spain

7. Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain

8. Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Prince of Asturias, Networking Research Center on for Liver and Digestive Diseases (CIBEREHD), 28806 Alcalá de Henares, Spain

9. Pathological Anatomy Service, University Hospital Gómez-Ulla, 28806 Alcalá de Henares, Spain

Abstract

Preeclampsia (PE) is a serious hypertensive disorder affecting 4–5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.

Funder

Instituto de Salud Carlos III

European Development Regional Fund

Comunidad de Madrid

ProACapital

Publisher

MDPI AG

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