Placental protein may offer clues to early brain development

The placenta, the temporary organ that forms during pregnancy to carry oxygen and nutrients from mother to baby, is vital to healthy gestation, yet it remains understudied.

While its function and purpose are well-established, far less is known about what problems can occur there, and their impacts on mother and child.

“What is it about the placenta that has to go right for the baby’s development, and what are the things that keep it going on a healthy trajectory?” said John Chappell, associate professor at the Fralin Biomedical Research Institute at VTC. As a vascular biologist, Chappell’s investigation focuses on blood vessel development. 

Chappell and his team have identified a protein not previously found in the placenta that plays a role in infant vascular development and potentially affects maternal health. Their discovery is described in a new article published in Angiogenesis.

“This new finding gives us baseline levels of this protein in a healthy, developing placenta,” said Audra Barnes-Lanier, a former graduate research assistant in Chappell’s lab and the paper’s first author. “We found that it is oxygen sensitive and may potentially serve as a new therapeutic target for pregnancy disorders such as preeclampsia.”

The discovery challenges established belief that the protein — soluble platelet-derived growth factor receptor beta, or sR-beta — is merely a biomarker of pericyte cell death in the brain.

Chappell’s research found the protein isn’t just present during pericyte death, but during vascular development, as well. Pericyte cells help provide structure to blood vessels. Determining the protein’s function in the placenta is the next aim. 

“Nature doesn't put cells anywhere unless it's on purpose. We believe sR-beta is likely involved in some sort of pathway modulation, to keep pericyte development in check,” said Chappell, who also holds an appointment in Virginia Tech’s Department of Biomedical Engineering in the College of Engineering. “We want to know what causes it to be mis-regulated in its production. And then, if it becomes mis-regulated during gestation, what does that mean for pregnancy outcomes?”

He believes that too much or not enough of the protein could negatively impact neurovascular development in the brain, causing both acute and chronic problems in the developing baby. 

The effects, Chappell hypothesizes, could include brain bleeds, a potentially life-threatening condition in which blood vessels leak or rupture, and retinopathy, eye damage from inadequate blood flow. 

The lab has more to learn about the protein and its role, but Chappell believes its first potential clinical use could be as a biomarker that could alert doctors to potential neurodevelopmental issues.

 A richer understanding of the protein and its function, Chappell said, could point to therapeutic targets to prevent or limit those neurodevelopmental problems. 

“The next step of this project is to investigate how this protein changes during placental distress,” Barnes-Lanier said.

“We have a lot of work to do,” Chappell said, “but this is an important finding that changes the understanding of the location and purpose of this protein, and it sheds much needed light on the placenta, which is important to the mother’s well-being and sets the stage for a baby’s life-long health.”

The research was funded by a grant from the Seale Innovation Fund at the Fralin Biomedical Research Institute.