Calcifying nanoparticles under a scanning electron microscope. Photo courtesy of NASA.
Preterm birth is on the rise in the United States, with one in eight children born prematurely. A menace to the medical community, preterm birth is a leading cause of newborn death and lifelong disability. Even though many causes of premature birth remain unknown, a number of them have been identified, such as infection, placental bleeding, and stress on the mother. Premature rupture of maternal membranes may also lead to preterm birth; however, the process by which this occurs is not known. In hopes to better understand this phenomenon, Lydia Shook MED ’13 and the rest of the lab of Dr. Irina Buhimschi, Associate Professor of Obstetrics, Gynecology, and Reproductive Sciences, have begun to investigate a possible mechanism for preterm birth.
Shook and the lab were aware of calcifying nanoparticles’ role in other debilitating conditions, such as arthritis and atherosclerosis. In these cases, the calcium deposits that occur due to the aggregates of these particles and calcium disrupt natural processes in joints and muscles. The Buhimschi lab, however, creatively decided to take these findings a step further and investigate if these particles could be part of a mechanism for premature rupturing of the membranes that lead to preterm birth. As a result, Shook hypothesized that these “calcifying nanoparticles form in the amniotic cavity and are involved in…pathways leading to preterm birth.”
How maternal stress can play into the pathogenesis of preterm birth. Image courtesy of Charles J. Lockwood.
Shook and her colleagues used histological techniques to look for deposition of calcium and expression of fetuin, a protein that associates with nanoparticles in tissue samples of fetal membranes and placenta collected from term and preterm deliveries. Shook and her colleagues then used a culture technique to see whether nanoparticles could form in the amniotic fluid. Finally, the group used electron microscopy to visualize the calcifying nanoparticles and tested the functional effect of these cultured nanoparticles on healthy fetal membranes.
The results of the study were very encouraging. The group found that fetuin and calcium were deposited in the same locations – the placenta and fetal membranes. After about four weeks of incubation, calcifying nanoparticles were observed in the amniotic fluid, which suggested that the lab’s hypothesized mechanism was possible. When Shook and her colleagues exposed fetal membrane tissue to the particles, the particles seemed to stimulate apoptotic pathways that did not involve inflammation. On the whole, the results seemed to support the lab’s hypotheses.
The findings of the lab are an important step towards identifying more warning signs for preterm delivery so that fewer women undergo such delivery and the risks that are associated with it. As Shook explains, one of the next steps to take may be to find markers that are not only associated with the calcifying nanoparticles but also easily testable. Consequently, if a pregnant woman’s amniocentesis (amniotic fluid test) returns with this marker, doctors can begin targeted therapy much earlier. Though Shook notes that these applications are still a ways away, they represent a pivotal step towards reducing death and disability due to premature birth.
