Nesfatin: predictor of placenta abnormalities?

WCVM scientists are working to identify effective predictors of placenta abnormalities that often lead to premature births.

Five to 10 per cent of the world’s pregnant women end up delivering their babies early — before a full term of 37 weeks. Once they’re born, these “pre-term” babies are at significant risk: 70 to 75 per cent of all newborn deaths or serious illness occur in pre-term babies.

Those grim statistics are a concern for Daniel MacPhee, an associate professor at the Western College of Veterinary Medicine (WCVM).

“In the past 30 years, the rate of pre-term birth has not diminished,” explains the reproductive biology researcher. 

“It’s not getting better, and it’s actually getting worse depending on where you live.”

Many pre-term issues are linked to abnormalities of the placenta, the bridge between fetal and maternal systems during pregnancy. These irregularities can have serious or potentially life-threatening consequences for the mother and her unborn child.

MacPhee is striving to better understand how the placenta normally develops. With this knowledge, he and other researchers can work to identify effective predictors of placental disease and/or better clinical strategies to improve health outcomes.

Improved knowledge may also reduce long-term health care costs for patients with placental abnormalities. MacPhee points to research showing that problems with the placenta during pregnancy have ramifications into adulthood.

For example, preeclampsia (dangerously high blood pressure in pregnant mothers) and fetal growth restriction (when fetal growth is limited in the uterus because of placental malfunction) are both linked to increased risk of adult diseases such as cardiovascular disease, type 2 diabetes and obesity.

“That five to 10 per cent of pre-term deliveries translates into billions of dollars per year in the health care system being spent to treat those individuals,” says MacPhee. “And the costs are not just as babies, but for the entire life of that individual.

“We should be thinking about how to make this better.”

MacPhee is working on a new research project in collaboration with Suraj Unniappan, an associate professor in the WCVM’s Department of Veterinary Biomedical Sciences. The study focuses on human and mouse placentae and a newly-discovered protein called nesfatin.

Nesfatin is described as a protein hormone — or a chemical messenger in the body. It’s been found in a variety of tissues in humans and mice including the pancreas, fatty tissue, digestive system, cardiovascular system and brain.

Previous studies have shown nesfatin to be important in the transport of sugars, secretion of insulin, regulation of energy balance and appetite — among other important functions.

So how exactly does nesfatin relate to pregnancy or placental abnormalities?

Reproductive biology researchers across the country are searching for potential biomarkers for placental disease. A biomarker is an indicator (such as a molecule or protein) that is associated with a certain disease or biological process in the body.

Once a biomarker has been identified and characterized, researchers can use changes in the marker levels to predict, diagnose and prevent clinical cases.

No reliable biomarker for placental disease exists, but MacPhee and his research team think that nesfatin could be a signal that would help researchers detect and prevent placental disease and pre-term births.

“We’re potentially laying the groundwork for preventing future disease and pre-term births,” MacPhee explains.

“I find [this research] to be really important – it’s what drives me.”

MacPhee began his investigation by looking at two main questions. First, is nesfatin in the placenta? And second, where and when is the protein found?

MacPhee’s research team answered these questions using specific lab techniques applied to human and mouse placentae. The researchers found that nesfatin was highly expressed in the outer cell layer of human placentas in all trimesters of pregnancy. They also found the protein in similar structures within the mouse placenta.

Although this research is still in the early stages, MacPhee says the possibilities for future projects are numerous – especially since they have found nesfatin in the placenta throughout all stages of pregnancy.

In ongoing research, MacPhee aims to compare the expression of nesfatin in healthy human placentae versus placentae from complicated pregnancies. More specifically, his research team will try to pinpoint exactly where nesfatin is found within cells.

Taking a “One Health” approach, his team will also study placentae from domestic animal species as a means of helping human and veterinary researchers learn more about placental dysfunction in people as well as in animals.

“In a sense we’ve found something new that no one else has reported,” says MacPhee. “We definitely want to push forward and explore this.”

Crystalyn Legg-St. Pierre of Edmonton, Alta., is a second-year veterinary student who is part of the WCVM’s Undergraduate Summer Research and Leadership program in 2014. Crystalyn’s story is part of a series of articles written by WCVM summer research students. 

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