(L-459) Elucidating the Effects of Pregnancy on Liver Functions Using Engineered Liver Co-cultures

During pregnancy, the liver increases its size, lipid and bile acid production, and cytochrome P450 (CYP) enzyme activities; such changes can alter drug pharmacokinetics, thereby predisposing individuals to premature delivery, pregnancy loss, and/or infant birth defects. Due to the inability of accessing human liver tissue during pregnancy, mice are important for investigating pregnancy’s effects on liver metabolism. In vitro platforms complement in vivo studies for dissecting molecular mechanisms and for high-throughput chemical screening; however, primary mouse hepatocytes (PMHs) rapidly decline in function within 2D monocultures, and protocols for culturing hepatocytes from pregnant mice are not reported. Thus, we utilized a functionally stable micropatterned co-culture (MPCC) platform of PMHs from pregnant and non-pregnant mice incubated in sera extracted from such mice. We then tested the novel hypothesis that blood-borne pregnancy factors in sera can induce variations in hepatic functions that correlate with in vivo outcomes.