Mizzou Researchers Use Novel Method to Uncover Impact of Maternal Oxycodone on Placental Cells

Published 11/6/2024

Cheryl Rosenfeld

Cheryl Rosenfeld, DVM, PhD, professor at the University of Missouri College of Veterinary Medicine, recently published research titled “Effects of Oxycodone on Placental Lineages: Evidence from the Transcriptome Profile of Mouse Trophoblast Giants Cells” in the Proceedings of the National Academy of Sciences. Rosenfeld worked alongside Zhen Lyu, Jessica Kinkade, Nathan Bivens, Michael Roberts and Trupti Joshi, each with affiliations across different departments at Mizzou. The research examines how the consumption of opioid drugs by the mother may impact the placenta.

“The placenta is the primary communication organ between the mother and fetus during pregnancy,” says Rosenfeld. “It is becoming increasingly clear that what we are exposed to during in utero or fetal life, such as oxycodone, can lead to lifelong consequences in that it can increase our risk for a variety of diseases, such as cardiovascular and neurodevelopmental disorders, such as autism spectrum disorders.”

The current studies used mice, due to the commonalities that the mouse and human placentas share in structure, as the fetal placenta invades deeply into the underlying uterus that supports fetal growth and general function that allows for the exchange of gasses, nutrients and waste products from the fetus to the mother. Within humans, extravillous trophoblast cells invade deeply into the underlying uterine tissue and even blood vessels. Abnormal development of these cells can lead to preeclampsia, a pregnancy disorder in which the mother experiences severe hypertension that can increase the risk for morbidity and mortality to her and her fetus. The closest cell type in the mouse placenta to the extravillous trophoblast cell is called the parietal trophoblast giant cell that is in direct proximity to the underlying uterus.

The giant cells within these mice made it difficult for previous researchers to characterize the normal genes these cells express, which would allow us to better understand these cells and potential commonalities to human extravillous trophoblast cells. Previous attempts were based on a filter approach, and these cells are bigger than the filter, keeping them from passing through. For this reason, Rosenfeld’s research used a different and newly designed method. “We used a recently developed approach that does not use a filter but fixes each nuclei and then places a barcode on each cell, such that we can then link the gene expression profile to individual cells,” Rosenfeld said. “By using this approach, we are the first group to be able to characterize the normal genes expressed by these giant cells at later stages of pregnancy. We have shown that these cells are vulnerable to maternal treatment with oxycodone in that this drug nearly obliterates their normal expression.”

Rosenfeld points out that the placenta likely holds the key in understanding how the challenges encountered during fetal life can lead to lifelong consequences.

“By understanding how factors such as oxycodone affect the placenta and specific trophoblast cells in the placenta, it will pave the way for early detection methods based on such placenta changes, such that we can identify, before even any clinical signs have manifested, what diseases a newborn might be at risk for, and based on this knowledge, we might be able to develop early treatments to prevent such diseases from ever occurring,” Rosenfeld says.

Rosenfeld says the importance of the “One Health” approach, a collaborative, multisectoral and transdisciplinary approach with the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, plants and our shared environment, cannot be understated. “Our research, like that of many others, is borne out from the idea of a “One Health” approach, in that diverse animals and humans are impacted by environmental challenges from fetal life onwards,” says Rosenfeld. “It’s these animal models that can shine that light and provide critical insight into what we know is going on and how we might be able to combat harmful factors experienced early on. Thus, animals can teach us a great deal about ourselves.”