Date of Award

January 2021

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Clare Flannery

Second Advisor

Seth Guller

Abstract

AN EX VIVO MODEL OF GLYCOGEN SYNTHESIS IN PLACENTAL EXPLANT TISSUE

Pavithra Vijayakumar, Patricia Xu, Katie Cooke, Anika Anam, Jane O’Bryan, Zhonghua Tang, and Clare Flannery. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, School of Medicine, New Haven, CT.

As rates of maternal obesity rise, a better understanding of how the maternal metabolic environment influences fetal outcomes is required to inform further clinical and therapeutic investigations. In particular, the role that glycogen storage plays in mediating nutrient delivery to the fetus is still unclear; understand this process could help explain disparate outcomes in pregnant women with obesity. We aim to develop an ex vivo model of placental metabolism that is able to capture aerobic respiration at physiologic levels and characterize the metabolic pathways at use by placental tissue in this model. We collected thirteen placentas from women undergoing cesarean delivery without trial of labor, who were known to not have gestational or pre-existing diabetes, and cultured explants from these placentas under varying media, time, and oxygen conditions. We found that lactate levels were very high in explants cultured at 20% oxygen, and that the presence of gluconeogenic substrates in addition to glucose increased the production and accumulation of glycogen. We then found that glycogen levels were increased in placenta cultured at 50% oxygen, and that glycogen levels decline over the first few hours of culture before rising and peaking at around 8 hours of treatment. We were able to minimize the initial loss of glycogen by optimizing the protocols used for processing tissue both before and after explant culture. Using this model of metabolism, we hope to continue to work with the IOMIC core at Yale to further characterize the metabolic fate of glucose under these conditions.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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