Cyclin-dependent Kinase Inhibitor 2A (Placental Senescence Marker) on Labor-related Signals

May 9, 2023 updated by: Fatma El-sayed Moustafa, Assiut University

The Role of Cyclin-dependent Kinase Inhibitor 2A (P16 INK4a) (Placental Senescence Marker) on Labor-related Signals Through Progesterone Receptors Expression in Human Placenta

Onset of labor in human is initiated by progesterone withdrawal. Over many decades researchers had proposed hypotheses to explain the functional withdrawal of progesterone. These hypotheses were through the sequestration of active progesterone by corticosteroid-binding globulin, a decrease in active progesterone metabolite levels and changes in the ratio of progesterone receptor (PR) isoforms (nuclear progesterone receptors A (nPRA) and nuclear progesterone receptors B (nPRB)). Progesterone performs its action non-genomically through binding to membrane receptors and genomically via binding to nPRs. PRA is the less active or inactive form of progesterone receptors and shorter in amino acid sequence than PRB, the active form of the receptors.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Another mechanism was done through transcriptional co-activators, repressors inflammation resulting in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) mediated PR suppression. Previous study had explored that the uterine myometrium as the site of this functional withdrawal. There is also a clock that can determine the length of human pregnancy resides in the placenta and functional progesterone withdrawal likely occurs in this organ as well.

Ageing is a process that causes deterioration in function at the cellular, tissue and organ levels. Telomeres are protective caps made of nucleoprotein molecules located at the end of chromosomes and are necessary for protection against breaks at DNA ends, fusion of chromosome ends and chromosome degradation.

Telomeres are shortened with each cell division. The rate at which this occurs is accelerated by certain stressors such as oxidative stress. When telomeres reach a dangerously short length the process of cellular senescence initiates through which cells irreversibly stop growing and dividing by arresting their cell cycle and gradually ageing (becoming senescent).

Cellular senescence is a state of irreversible cell cycle arrest resulting from high levels of P16 INK4a as well as tumour 15 suppressors p53 and retinoblastoma tumour suppressor protein. Senescent cells markedly have an ability to change gene expression patterns with overexpression of anti-apoptotic Bcl-2 leading to resistance to apoptosis and in parallel increase NFκB activity results in the expression of proinflammatory cytokines and chemokines. As pregnancy comes to term, decidual cells show many features of senescence including secretion of senescence-associated secretory phenotype (SASP) factors such as interleukin-6 (IL-6). A gradual process of decidual senescence may be critical for driving the cellular and tissue changes that contribute to labor onset at term. If ageing of the placenta normally determines pregnancy duration, this means that premature placental ageing will lead to preterm labor onset.

According to World Health Organization (WHO), the American Academy of Pediatrics (AAP), and the American College of Obstetricians and Gynecologists (ACOG), preterm birth is defend as babies born alive before 37 weeks of pregnancy are completed. Each year, 15million babies are born preterm in the world. The National Center for Health Statistics of the Centers for Disease Control and Prevention generally reports data on three categories of preterm birth: overall preterm (< 37 weeks 'gestation), moderately preterm (between 32 and 36 weeks' gestation) and very preterm births (< 32 weeks' gestation). Late preterm infants are born at a gestational age between 34 weeks and less than37 weeks.

Study Type

Observational

Enrollment (Anticipated)

81

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Mahmoud Raafat Abdel-fadeil, professor
  • Phone Number: 0201001644429
  • Email: mrafadeil@gmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Pregnant women who will come for termination of pregnancy

Description

Inclusion Criteria:

  • Pregnant women who will come for termination of pregnancy by caesarean section or vaginal delivery.
  • Gestational age is between 28 to < 37 weeks for preterm labor and 37 to 40 weeks for term labor.
  • The age range of women is between18- 40 years.

Exclusion Criteria:

  • Acute or chronic infectious diseases or other chronic illness
  • Autoimmune diseases
  • PE complicated with Eclampsia, DIC or HELP syndrome
  • Congenital anomaly of the uterus
  • History of trauma
  • Twins pregnancy
  • Congenital anomalies of the fetus
  • Fetal growth restriction

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
1
Women in preterm delivery with GA < 36 weeks.
2
Women not in labor undergoing elective C-section with GA between 36 and 40 weeks.
3
Women following spontaneous labor (without being induced) with GA between 36 and 40 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
P16 INK4a
Time Frame: one year
1.Evaluating the role of cyclin-dependent kinase inhibitor 2A (P16 INK4a) placental senescence marker to predict time of labor.
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PR
Time Frame: one year
2.Local effect of cyclin-dependent kinase inhibitor 2A (P16 INK4a) placental senescence marker on progesterone receptors expression in human placenta.
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2023

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

February 1, 2025

Study Registration Dates

First Submitted

May 9, 2023

First Submitted That Met QC Criteria

May 9, 2023

First Posted (Actual)

May 18, 2023

Study Record Updates

Last Update Posted (Actual)

May 18, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P16 INK4a and PR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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