OC 25.1 - Platelet Derived Growth Factor-B is increased during intrauterine growth restriction induced by thromboxane A2

Sunday, June 25, 2023

14:45 – 15:00 ET

Room: 511

Session Available As: On-Demand

Presenting Author(s)

Marina Leardini-Tristao, PhD (she/her/hers)

Post doctoral fellow
The University of Utah, Salt Lake City, UT, USA
Salt Lake City, Utah, United States

Co-Author(s)

EM

Emilie Montenont, PhD

Post doctoral fellow
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA
Salt Lake City, Utah, United States
CV

Claudia V de Araujo

Research Associate
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA
Salt Lake City, Utah, United States
SJ

Shancy Jacob

Post Doctoral Fellow
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA
Salt Lake City, Utah, United States
YK

Yasuhiro Kosaka

Research Scientist
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA
Salt Lake City, Utah, United States
AS

Ashley S Brown

Sr Laboratory Specialist
Division of Pediatric Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah
Salt Lake City, Utah, United States
CF

Camille Fung

Associate Professor (Clinical)
Division of Pediatric Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah
Salt Lake City, Utah, United States
Robert A. Campbell, PhD

Professor
University of Utah, Salt Lake City, UT, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
Salt Lake City, Utah, United States
Matthew T. Rondina, MD

Professor
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 4George E. Wahlen Department of Veterans Affairs Medical Center, Geriatric Research, Education, and Clinical Center; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA
Salt Lake City, Utah, United States

Background: Intrauterine growth restriction (IUGR) refers to suboptimal growth in utero and is often a result of uteroplacental insufficiency. Platelets are important regulators of angiogenesis, storing growth factors such as platelet-derived factor B (PDGF-B) in α granules. Whether or not platelets mediate IUGR remains unknown.

Aims: We hypothesized that during IUGR, platelets release PDGF-B as a compensatory mechanism to maintain placental vascular development and fetal growth.

Methods: Elevated thromboxane A2 (TXA2) levels are seen in complications of hypertensive disease of pregnancy (HDP) causing IUGR. We used an established murine model of IUGR induced by TXA2. Pregnant C57Bl/6 mice had a micro-osmotic pump administering either the TXA2 analog U46619 (4µg/µL) or sham (0.5% ethanol) implanted retroperitoneally on embryonic day 12.5 for 6.5 days. At embryonic day 19, fetal and maternal blood were collected for platelet assays and placenta tissue for microscopy. We used unpaired Student’s t test and differences with p< 0.05 were considered significant.

Results: Offspring exposed to TXA2 had significant lower weights and placental efficiency compared to the sham group, consistent with IUGR. Maternal plasma 11-dehydro-TXB2 levels (a metabolite of TXA2) were also increased in the TXA2 group. Placenta vasculature organization and formation, analyzed by CD31 staining, was significantly reduced in the TXA2 group. Maternal platelet count was modestly, but significantly, lower in TXA2 mice (813 ± 22 vs. 730 ± 24), while white and red blood cell counts were similar between groups. PDGF-B protein was significantly higher (p < 0.05) in maternal plasma and significantly lower in maternal platelets in the TXA2 group, suggesting that platelets may release PDGF-B in response to TXA2.

Conclusion(s): These findings define new biological roles of PDGF-B in IUGR. As pregnancy complications such as HDP causing IUGR are associated with increased mortality and morbidity, our studies may help fill important knowledge gaps for maternal and fetal health.

Learning Objectives:

After participating in this session, attendees should be able to understand intrauterine growth restriction as a common consequence in hypertensive disorders of pregnancy (HDP).
After participating in this session, attendees should be able to recognize the potential role of platelets alpha granules released during pregnancy complications.
After participating in this session, participants should be able to understand the relevance of PDGF-B as an important growth factor, which can act as a compensatory mechanism during PDH, improving IUGR and, consequently, improving the outcome during complications of HDP.