Hypoxia-induced Autophagy in the Pathogenesis of MAP

Assiut University80 enrolled

Overview

To investigate the role of HIF 1α and LC3B in the pathogenesis of MAP, to evaluate the role of MMP-9 in the antenatal prediction of MAP, and to compare the expression of HIF1α, LC3B, and level MMP-9 between patients of placenta previa with MAP and patients with normal placentation.

Cesarean section (CS) rate has been rising rapidly in the recent years.One of the complications of repeated CS is placenta previa, an implantation of placenta on or near internal os. Morbidly adherent placenta (MAP), known also as placenta accreta spectrum, has histopathologic and clinical types. The placenta becomes abnormally adherent to the uterine wall, fails to separate leading to massive blood loss and possible hysterectomy. The risk of MAP in patient with placenta previa increases with repeated CS. Theories for development of MAP include abnormal trophoblastic invasion of myometrium, abnormal decidualization, neovascularization and reduction of apoptosis of trophobalsts. In early pregnancy: the trophoblasts invade spiral arteries and reduce blood flow to the placenta 00leading to hypoxia. Hypoxia inducible factor 1 alpha (HIF-1α), a protein involved in cellular adaptation to hypoxia, increases throughout pregnancy and contributes in the invasion of trophoblasts. Excessive invasion in MAP might prolong the hypoxia, increasing the expression of HIF1α. Autophagy is a process for managing and removing the damaged organelles and cellular proteins in hypoxia. It supports the trophoblasts. Hypoxia induced autophagy markers such as LC3B might be enhanced by MAP. Matrix metalloproteinase-9 (MMP-9) plays an important role in cell invasion and placental implantation. Disturbance of MMP-9 might alter the trophobalsts invasion resulting in MAP . The investigators hypothesize that hypoxia, autophagy and invasiveness are linked to the pathophysiology of MAP, so we will assess the expression of HIF1α, LC3B to estimate their role beside MMP-9.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Hypoxia Autophagy Placenta Morbidly Adherent Placenta

Interventions

HIF 1α and LC3B expression and MMP-9 levelDIAGNOSTIC_TEST

5ml of venous blood samples will be taken from all participants at 28-40 weeks of gestation for detcetion of MMP-9 level by Enzyme-Linked Immune Sorbent Assay (ELISA) kit. Placental tissue sample in the maternal surface will be taken during CS in placenta previa group and similar location in maternal surface will be sampled after placental delivery in control group for histopathology and immunohistochemistry for detection of HIF 1α and LC3B expression

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Gestational age: more than 28 weeks up to 40 weeks. 2. Pregnant women with at least one previous CS. 3. Singleton pregnancy. 4. Patient known to have placenta previa by 2D ultrasound. 5. Heamodynamically stable patient. Exclusion Criteria: 1. Multiple pregnancy. 2. Gestational age less than 28 weeks. 3. Heamodynamically unstable patient. 4. Hypertensive disorder with pregnancy. 5. Gestational diabetes. 6. IUGR. 7. Patient with bleeding tendency or using anticoagulant.

Outcomes

Primary Outcomes

Compare the expression of HIF 1α and LC3B by immunohistochemistry and the level of MMP-9

To explore the mechanism of abnormal trophoblasts invasion in MAP.

Time frame: 28-40 weeks of gestation.

Secondary Outcomes

Measure MMP-9 concentration in the maternal plasma

To verify its usefulness as an antenatal predictor of MAP

Time frame: 28-40 weeks of gestation.

Central Contacts

Nermeen Bahaa ElDien Mohamed Ahmed, dr

CONTACT

01011126294 nermeenbahaa11@gmail.com

Dalia Gamal El-Din Mostafa Morsy, prof dr

CONTACT

01111948221 dalia_gamal66@yahoo.com

Data from ClinicalTrials.gov

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