Hippo-YAP Pathway and Related miRNAs in Preterm Birth (HIPPO-PTB)

July 8, 2026 updated by: Nazan Yurtcu MD, Cumhuriyet University

Analysis of Hippo-YAP Pathway Genes and Proteins and Related miRNA-195, miRNA-181c, miRNA-200a, and miRNA-375 Expression in Maternal Blood, Placental Tissue, and Myometrial Tissue From Women With Term and Preterm Cesarean Delivery

This completed observational study evaluated the expression of Hippo-YAP pathway-related genes and proteins and selected microRNAs in maternal blood, placental tissue, and myometrial tissue obtained from women who underwent cesarean delivery at term or preterm gestational ages.

The study compared women with spontaneous preterm delivery and women with term delivery. Maternal blood, placental tissue, and myometrial tissue samples were analyzed using molecular, biochemical, and immunohistochemical methods to explore whether Hippo-YAP pathway activity and related miRNA expression patterns may be associated with the pathophysiology of preterm birth.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Preterm birth remains an important obstetric condition associated with neonatal morbidity and mortality. Although clinical risk factors for preterm birth are well described, the underlying molecular mechanisms are not fully understood. Inflammation, immune regulation, placental function, and myometrial activity are considered important components of the biological processes leading to preterm labor and delivery.

The Hippo-YAP signaling pathway is involved in cellular proliferation, differentiation, tissue homeostasis, immune regulation, and placental biology. Several microRNAs are also known to regulate reproductive tissues, placental function, myometrial activity, and inflammatory pathways. Based on this biological background, this study investigated the Hippo-YAP pathway and selected related microRNAs in maternal blood, placental tissue, and myometrial tissue from women with term and preterm cesarean delivery.

This was a completed observational case-control biomarker study. Participants were not assigned to any intervention. The study included two groups: women who delivered preterm and women who delivered at term. Maternal blood samples were collected before cesarean delivery. Placental tissue samples were obtained after delivery, and myometrial tissue samples were collected from the placental bed during cesarean section. Samples were stored under appropriate laboratory conditions until analysis.

The study evaluated the expression of Hippo-YAP pathway-related genes and proteins, including MST1, LATS1, YAP1, TAZ, MAP4K1, and PIK3C2B, as well as selected related microRNAs, including miRNA-195, miRNA-181c, miRNA-200a, and miRNA-375. Gene and microRNA expression analyses were performed using quantitative real-time polymerase chain reaction. Protein expression was assessed using enzyme-linked immunosorbent assay and immunohistochemistry.

The primary objective was to compare Hippo-YAP pathway-related gene, protein, and microRNA expression patterns between preterm and term delivery groups. Secondary objectives included evaluating expression patterns across maternal blood, placental tissue, and myometrial tissue and exploring whether these molecular differences may contribute to understanding the biological mechanisms involved in preterm birth.

The study was approved by the Sivas Cumhuriyet University Clinical Research Ethics Committee. Written informed consent was obtained from participating women. The project was supported by the Scientific and Technological Research Council of Türkiye (TUBITAK), project number 121S414, and the immunohistochemistry experiments were additionally supported by a complementary research grant, project number T-2022-954-D7.

This study was retrospectively registered after completion of participant enrollment, sample collection, and laboratory analyses for transparency.

Study Type

Observational

Enrollment (Actual)

44

Contacts and Locations

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

Study Locations

  • Turkey (Türkiye)
    • Kayseri Ave
      • Sivas, Kayseri Ave, Turkey (Türkiye), 58140
        • Sivas Cumhuriyet University Faculty of Medicine

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

Non-Probability Sample

Study Population

Pregnant women who underwent cesarean delivery at Sivas Cumhuriyet University Faculty of Medicine and were included in either the spontaneous preterm delivery group or the term delivery comparison group.

Description

Inclusion Criteria:

- cInclusion Criteria:

  • Pregnant women aged 18 years or older
  • Singleton pregnancy
  • Women who underwent cesarean delivery
  • For the preterm delivery group: spontaneous preterm labor and delivery between 24 and 34 weeks of gestation
  • For the term delivery group: cesarean delivery at term gestational age without active labor
  • Written informed consent for participation and collection of maternal blood, placental tissue, and myometrial tissue samples

Exclusion Criteria:

  • Multiple pregnancy
  • Major fetal anomaly
  • Clinical evidence of chorioamnionitis
  • Hypertensive disorders of pregnancy
  • Diabetes mellitus or gestational diabetes mellitus
  • Autoimmune disease
  • Chronic inflammatory disease
  • Maternal systemic infection
  • Placental abruption
  • Premature rupture of membranes, if excluded in the original protocol
  • Use of medications or presence of maternal conditions that could significantly affect inflammatory, molecular, or placental biomarker expression
  • Refusal to provide informed consent

Exclusion Criteria:

-

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
Intervention / Treatment
Preterm Delivery Group
Women who underwent cesarean delivery between 24 and 34 weeks of gestation after spontaneous preterm labor. Maternal blood, placental tissue, and myometrial tissue samples were collected for molecular, biochemical, and immunohistochemical analyses.
Other: Laboratory Biomarker Analysis
Laboratory analysis of maternal blood, placental tissue, and myometrial tissue samples for Hippo-YAP pathway-related gene, protein, and microRNA expression. No treatment or clinical intervention was assigned to participants.
Term Delivery Group
Women who underwent cesarean delivery after 39 weeks of gestation without active labor. Maternal blood, placental tissue, and myometrial tissue samples were collected as the term delivery comparison group.
Other: Laboratory Biomarker Analysis
Laboratory analysis of maternal blood, placental tissue, and myometrial tissue samples for Hippo-YAP pathway-related gene, protein, and microRNA expression. No treatment or clinical intervention was assigned to participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expression levels of Hippo-YAP pathway-related genes, proteins, and selected microRNAs
Time Frame: Perioperative/Periprocedural
Expression levels of Hippo-YAP pathway-related genes and proteins, including MST1, LATS1, YAP1, TAZ, MAP4K1, and PIK3C2B, and selected microRNAs, including miRNA-195, miRNA-181c, miRNA-200a, and miRNA-375, were compared between women with preterm delivery and women with term delivery using maternal blood, placental tissue, and myometrial tissue samples.
Perioperative/Periprocedural

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tissue-specific expression patterns of Hippo-YAP pathway biomarkers and related microRNAs
Time Frame: Perioperative/Periprocedural
Expression patterns of Hippo-YAP pathway-related genes, proteins, and selected microRNAs were evaluated across maternal blood, placental tissue, and myometrial tissue samples to explore tissue-specific molecular differences between preterm and term delivery groups.
Perioperative/Periprocedural

Collaborators and Investigators

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

Sponsor

Cumhuriyet University

Collaborators

The Scientific and Technological Research Council of Turkey

Investigators

  • Principal Investigator: Nazan Yurtcu, MD, PhD, Cumhuriyet 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 (Actual)

June 1, 2021

Primary Completion (Actual)

April 1, 2024

Study Completion (Actual)

May 31, 2024

Study Registration Dates

First Submitted

July 2, 2026

First Submitted That Met QC Criteria

July 8, 2026

First Posted (Actual)

July 10, 2026

Study Record Updates

Last Update Posted (Actual)

July 10, 2026

Last Update Submitted That Met QC Criteria

July 8, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TUBITAK-121S414
  • 121S414 (Other Grant/Funding Number: The Scientific and Technological Research Council of Türkiye (TÜBİTAK), 1002 Rapid Support Program)
  • T-2022-954 (Other Grant/Funding Number: Sivas Cumhuriyet University BAP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared because no prospective data-sharing consent for public individual-level data sharing was obtained, and the dataset includes sensitive maternal clinical information and biological sample-related laboratory data.

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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