Browsing by Author "Soares, Michael J."

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    Gene profiling of maternal hepatic adaptations to pregnancy
    (Wiley Blackwell (Blackwell Publishing), 2010-03) Bustamante, Juan J.; Copple, Bryan L.; Soares, Michael J.; Dai, Guoli; Department of Biology, School of Science
    BACKGROUND: Maternal metabolic demands change dramatically during the course of gestation and must be co-ordinated with the needs of the developing placenta and fetus. The liver is critically involved in metabolism and other important functions. However, maternal hepatic adjustments to pregnancy are poorly understood. AIM: The aim of the study was to evaluate the influences of pregnancy on the maternal liver growth and gene expression profile. METHODS: Holtzman Sprague-Dawley rats were mated and sacrificed at various stages of gestation and post-partum. The maternal livers were analysed in gravimetric response, DNA content by PicoGreen dsDNA quantitation reagent, hepatocyte ploidy by flow cytometry and hepatocyte proliferation by ki-67 immunostaining. Gene expression profiling of non-pregnant and gestation d18.5 maternal hepatic tissue was analysed using a DNA microarray approach and partially verified by northern blot or quantitative real-time PCR analysis. RESULTS: During pregnancy, the liver exhibited approximately an 80% increase in size, proportional to the increase in body weight of the pregnant animals. The pregnancy-induced hepatomegaly was a physiological event of liver growth manifested by increases in maternal hepatic DNA content and hepatocyte proliferation. Pregnancy did not affect hepatocyte polyploidization. Pregnancy-dependent changes in hepatic expression were noted for a number of genes, including those associated with cell proliferation, cytokine signalling, liver regeneration and metabolism. CONCLUSIONS: The metabolic demands of pregnancy cause marked adjustments in maternal liver physiology. Central to these adjustments are an expansion in hepatic capacity and changes in hepatic gene expression. Our findings provide insights into pregnancy-dependent hepatic adaptations.
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    Maternal hepatic growth response to pregnancy in the mouse
    (SAGE, 2011-11) Dai, Guoli; Bustamante, Juan J.; Myronovych, Andriy; Zou, Yuhong; Bao, Qi; Kumar, Sudhanshu; Soares, Michael J.; Department of Biology, School of Science
    Pregnancy is characterized by physiological adjustments in the maternal compartment. In this investigation, the influence of pregnancy on maternal liver was examined in CD-1 mice. Dramatic changes were observed in the size of the maternal liver during pregnancy. Livers doubled in weight from the non-pregnant state to day 18 of pregnancy. The pregnancy-induced hepatomegaly was a physiological event of liver growth confirmed by DNA content increase and detection of hepatocyte hyperplasia and hypertrophy. Growth of the liver was initiated following implantation and peaked at parturition. The expression and/or activities of key genes known to regulate liver regeneration, a phenomenon of liver growth compensatory to liver mass loss, were investigated. The results showed that pregnancy-dependent liver growth was associated with interleukin (IL)-6, tumor necrosis factor α, c-Jun and IL-1β, but independent of hepatocyte growth factor, fibroblast growth factor 1, tumor necrosis factor receptor 1, constitutive androstane receptor and pregnane X receptor. Furthermore, maternal liver growth was associated with the activation of hepatic signal transducer and activator of transcription 3, β-catenin and epidermal growth factor receptor, but pregnancy did not activate hepatic c-Met. The findings suggest that the molecular mechanisms regulating pregnancy-induced liver growth and injury-induced liver regeneration exhibit overlapping features but are not identical. In summary, the liver of the mouse adapts to the demands of pregnancy via a dramatic growth response driven by hepatocyte proliferation and size increase.
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    Relative expression of proprotein convertases in rat ovaries during pregnancy
    (Springer Nature, 2013-12-11) Kwok, Simon C. M.; Chakraborty, Damayanti; Soares, Michael J.; Dai, Guoli; Biology, School of Science
    Background: Proprotein convertases are a family of serine proteinases that are related to bacterial subtilisin and yeast kexin. They are involved in posttranslational processing of the precursors of a vast number of cellular proteins. With the exception of PC1/3, the relative expression levels of the proprotein convertases in the ovary during pregnancy have not been reported. The purpose of this study is to determine by real-time PCR the relative expression levels of all nine proprotein convertases in rat ovaries during pregnancy and at 3 days postpartum. Methods: RNA was extracted from ovaries at Day 0, 4, 9, 11, 13, 15, 18, and 20 of pregnancy as well as 3 days postpartum. Relative expression levels of Pcsk1, Pcsk2, Furin, Pcsk4, Pcsk5, Pcsk6, Pcsk7, Mbtps1 and Pcsk9 were determined with real-time PCR. Results were reported as fold-change over the level at Day 0 of pregnancy. Results: Results showed that Pcsk1 and Pcsk6 were upregulated as gestation advanced, in parallel with an observed increase in relaxin transcript. Pcsk2 showed downregulation as gestation advanced, while Pcsk5 showed relatively higher levels in early pregnancy and postpartum, but lower level in mid-pregnancy. On the other hand, Furin, Pcsk4, Pcsk7, Mbtps1 and Pcsk9 showed little change of expression throughout gestation. Conclusion: PC1/3 (PCSK1) and PACE4 (PCSK6) may play an important role in proprotein processing in the ovary during late pregnancy.