BIOLOGY OF PREGNANCY AND IMMUNE FUNCTION
7:30 AM-10:00 AM
(320) HEPATOMEGALY AND HEPATIC GENE EXPRESSION DURING PREGNANCY IN THE MOUSE.
Dai, Guoli1, Peal, Mary1, Soares, Michael1, 1 Department of Molecular and Integrative Physiology, Kansas City, KS
ABSTRACT- Pregnancy is characterized by physiological adjustments in the maternal compartment. These include alterations in the functioning of virtually every organ system. Maternal metabolic demands change dramatically during the course of gestation and must be coordinated with the needs of the developing placenta and fetus. The liver is fundamentally involved in metabolism and other important functions. However, maternal hepatic adjustments to pregnancy are poorly understood. In this investigation, the influence of pregnancy on liver growth and gene expression was examined. CD-1 mice were mated and sacrificed at various stages of gestation. Tissues were harvested, weighed, frozen, and stored for subsequent analyses. Litter size in the pregnant mice ranged from 10-16 embryos. Dramatic changes were observed in the size of the maternal liver during pregnancy, especially when compared to the size of the heart and kidneys. Livers doubled in weight from the nonpregnant state to day 18 of pregnancy. Growth of the liver was initiated following implantation and was linear until day 13 of gestation. This growth phase correlated with placentation and the elaboration of placental lactogens. Following day 13 of gestation, the size of the liver stabilized and additional growth was modest and correlated with a change in the range of hormones produced by the placenta during the latter stages of pregnancy. Significant structural changes in the organization of the liver were not apparent by light microscopy. Gene expression profiles were compared between livers from nonpregnant and pregnant mice using a DNA microarray strategy. Data from three independent DNA microarray analyses from each treatment group were collected. The expression of numerous genes was impacted by pregnancy, including those involved in regulating cell proliferation, differentiation, and survival, extracellular matrix remodeling, intracellular transport of lipids, and serum transport of hormones. In summary, the liver of the mouse accommodates to the demands of pregnancy via a dramatic increase in its size and significant adjustments in its gene expression profile. (Supported by the Andrew Mellon Foundation and the NICHD: HD20676, HD37123)
KEY WORDS: hepatomegaly, pregnancy, liver, gene expression