Hypoxia-induced Autophagy in the Pathogenesis of MAP

NCT05817448 | Unknown

• 1 other identifier: hypoxia in MAP
• Study Type: observational
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hypoxia; Autophagy; Placenta; Morbidly Adherent Placenta

Keywords

HIF1α; hypoxia-induced autophagy; LC3B; invasion-related markers; MMP-9; Morbidly Adherent Placenta

Outcome Measures

Primary Outcomes (1)

• 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.

  28-40 weeks of gestation.

Secondary Outcomes (1)

• Measure MMP-9 concentration in the maternal plasma

  28-40 weeks of gestation.

Study Arms (2)

control group

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

Diagnostic Test: HIF 1α and LC3B expression and MMP-9 level

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

Diagnostic Test: HIF 1α and LC3B expression and MMP-9 level

Interventions

HIF 1α and LC3B expression and MMP-9 level 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

control group; placenta previa group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

selected from out patient's clinic of the department of Obstetrics and Gynecology at Assiut University Hospital, Assiut, Egypt,

You may qualify if:

• Gestational age: more than 28 weeks up to 40 weeks.
• Pregnant women with at least one previous CS.
• Singleton pregnancy.
• Patient known to have placenta previa by 2D ultrasound.
• Heamodynamically stable patient.

You may not qualify if:

• Multiple pregnancy.
• Gestational age less than 28 weeks.
• Heamodynamically unstable patient.
• Hypertensive disorder with pregnancy.
• Gestational diabetes.
• IUGR.
• Patient with bleeding tendency or using anticoagulant.

Sponsors & Collaborators

• Assiut University: lead

Related Publications (13)

• Morfaw F, Fundoh M, Bartoszko J, Mbuagbaw L, Thabane L. Using tocolysis in pregnant women with symptomatic placenta praevia does not significantly improve prenatal, perinatal, neonatal and maternal outcomes: a systematic review and meta-analysis. Syst Rev. 2018 Dec 27;7(1):249. doi: 10.1186/s13643-018-0923-2.

  PMID: 30591076 BACKGROUND

• Shainker SA, Silver RM, Modest AM, Hacker MR, Hecht JL, Salahuddin S, Dillon ST, Ciampa EJ, D'Alton ME, Otu HH, Abuhamad AZ, Einerson BD, Branch DW, Wylie BJ, Libermann TA, Karumanchi SA. Placenta accreta spectrum: biomarker discovery using plasma proteomics. Am J Obstet Gynecol. 2020 Sep;223(3):433.e1-433.e14. doi: 10.1016/j.ajog.2020.03.019. Epub 2020 Mar 19.

  PMID: 32199927 BACKGROUND

• Morlando M, Collins S. Placenta Accreta Spectrum Disorders: Challenges, Risks, and Management Strategies. Int J Womens Health. 2020 Nov 10;12:1033-1045. doi: 10.2147/IJWH.S224191. eCollection 2020.

  PMID: 33204176 BACKGROUND

• Faraji A, Akbarzadeh-Jahromi M, Bahrami S, Gharamani S, Raeisi Shahraki H, Kasraeian M, Vafaei H, Zare M, Asadi N. Predictive value of vascular endothelial growth factor and placenta growth factor for placenta accreta spectrum. J Obstet Gynaecol. 2022 Jul;42(5):900-905. doi: 10.1080/01443615.2021.1955337. Epub 2021 Sep 24.

  PMID: 34558384 BACKGROUND

• 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.

  PMID: 29446169 BACKGROUND

• 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.

  PMID: 28662825 BACKGROUND

• 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.

  PMID: 31269830 BACKGROUND

• Nakashima A, Tsuda S, Kusabiraki T, Aoki A, Ushijima A, Shima T, Cheng SB, Sharma S, Saito S. Current Understanding of Autophagy in Pregnancy. Int J Mol Sci. 2019 May 11;20(9):2342. doi: 10.3390/ijms20092342.

  PMID: 31083536 BACKGROUND

• Nakashima A, Aoki A, Kusabiraki T, Cheng SB, Sharma S, Saito S. Autophagy regulation in preeclampsia: Pros and cons. J Reprod Immunol. 2017 Sep;123:17-23. doi: 10.1016/j.jri.2017.08.006. Epub 2017 Aug 26.

  PMID: 28869810 BACKGROUND

• El-Hussieny M, Mohammed EM, Zenhom NM, Refaie MM, Okasha AM, Tawab MAE. Possible Role of TGF-beta1, MMP-2, E-CAD, beta-Catenin and Antioxidants in Pathogenesis of Placenta Accreta. Fetal Pediatr Pathol. 2021 Jun;40(3):222-232. doi: 10.1080/15513815.2020.1843574. Epub 2020 Nov 11.

  PMID: 33172328 BACKGROUND

• Gao F, Zhou C, Qiu W, Wu H, Li J, Peng J, Qiu M, Liang C, Gao J, Luo S. Total flavonoids from Semen Cuscutae target MMP9 and promote invasion of EVT cells via Notch/AKT/MAPK signaling pathways. Sci Rep. 2018 Nov 26;8(1):17342. doi: 10.1038/s41598-018-35732-6.

  PMID: 30478366 BACKGROUND

• 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.

  PMID: 35247287 BACKGROUND

• world health organisation. Rising rates suggest increasing numbers of medically unnecessary, potentially harmful procedures 2021 [cited 16 june 2021

  BACKGROUND

MeSH Terms

Conditions

Hypoxia; Placenta Accreta

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Placenta Diseases

Central Study 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

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Demonstrator at Physiology department

Study Record Dates

• First Submitted: April 5, 2023
• First Posted: April 18, 2023
• Study Start: September 1, 2023
• Primary Completion: September 1, 2024
• Study Completion: November 1, 2024
• Last Updated: May 24, 2023

Record last verified: 2023-05