Hypoxia-induced Autophagy in the Pathogenesis of MAP

NCT ID: NCT05817448

Last Updated: 2023-05-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-09-30

Study Completion Date

2024-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hypoxia Autophagy Placenta Morbidly Adherent Placenta

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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control group

40 pregnant women with normal placentation having no pregnancy related disorders according to the physical examination and laboratory findings.

HIF 1α and LC3B expression and MMP-9 level

Intervention Type DIAGNOSTIC_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

placenta previa group

40 pregnant women that will be diagnosed according to the ultrasound diagnostic criteria.

Then according to the histopathological examination, placenta previa group will be subdivided into 2 groups, placenta previa with MAP and placenta previa without MAP

HIF 1α and LC3B expression and MMP-9 level

Intervention Type DIAGNOSTIC_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

Interventions

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HIF 1α and LC3B expression and MMP-9 level

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Nermeen Bahaa El Dien Mohamed Ahmed

Demonstrator at Physiology department

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Nermeen Bahaa ElDien Mohamed Ahmed, dr

Role: CONTACT

01011126294

Dalia Gamal El-Din Mostafa Morsy, prof dr

Role: CONTACT

01111948221

References

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Seno K, Tanikawa N, Takahashi H, Ohkuchi A, Suzuki H, Matsubara S, Iwata H, Kuwayama T, Shirasuna K. Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells. Am J Reprod Immunol. 2018 Jun;79(6):e12826. doi: 10.1111/aji.12826. Epub 2018 Feb 15.

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Parrish AR. Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target. Prog Mol Biol Transl Sci. 2017;148:31-65. doi: 10.1016/bs.pmbts.2017.03.001. Epub 2017 May 4.

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Chen Y, Wang L, Bao J, Sha X, Cui L, Huang Q, Gu C, Li X, Liu H. Persistent hypoxia induced autophagy leading to invasiveness of trophoblasts in placenta accreta. J Matern Fetal Neonatal Med. 2021 Apr;34(8):1297-1303. doi: 10.1080/14767058.2019.1635582. Epub 2019 Jul 3.

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Fratelli N, Prefumo F, Maggi C, Cavalli C, Sciarrone A, Garofalo A, Viora E, Vergani P, Ornaghi S, Betti M, Vaglio Tessitore I, Cavaliere AF, Buongiorno S, Vidiri A, Fabbri E, Ferrazzi E, Maggi V, Cetin I, Frusca T, Ghi T, Kaihura C, Di Pasquo E, Stampalija T, Belcaro C, Quadrifoglio M, Veneziano M, Mecacci F, Simeone S, Locatelli A, Consonni S, Chianchiano N, Labate F, Cromi A, Bertucci E, Facchinetti F, Fichera A, Granata D, D'Antonio F, Foti F, Avagliano L, Bulfamante GP, Cali G; ADoPAD (Antenatal Diagnosis of Placental Adhesion Disorders) Working Group. Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study. Ultrasound Obstet Gynecol. 2022 Sep;60(3):381-389. doi: 10.1002/uog.24889.

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Other Identifiers

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hypoxia in MAP

Identifier Type: -

Identifier Source: org_study_id

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