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Guanghou Shui

Publications and source records attributed to Guanghou Shui.

2 recordsLinked to original sources
bioRxiv2015

Assisted reproduction causes intrauterus growth restriction by disrupting placental lipid metabolism

IVF related intrauterus growth restriction or low birth weight (LBW) is very common in ART clinic. This study is focus on the aberrant lipid metabolism induced by in vitro fertilization and its mechanism. Firstly, we investigated the effect of IVF on fetal weight and placenta efficiency at E18.5 (at birth) and E14.5 (middle gestation). Data shows that IVF caused LBW and low placenta efficiency. Then we studied the lipidomics of E18.5 placenta and E14.5 placenta. The IVF group has an eccentric lipid content compared to in vivo group. All the 15 lipid classes are largely accumulated in E18.5 IVF placenta and are deficient in E14.5 IVF placenta. In detail, most of the 287 lipid species is accumulated at E18.5 and went short at E14.5. Using qRT-PCR we detected the expression level of genes related to lipid uptake, transport and metabolism. Most of these genes are down-regulated which indicated the metabolism function of placenta is disrupted seriously. To the imprinted genes for lipid metabolism regulation as GNAS and Grb10, IVF not only disrupt their imprinting status (methylation level) but also disrupt their gene expression. The expression of DNMTs and Tets are also disrupted in the placenta. These data demonstrate that IVF impaired the regulation network of lipid metabolism. These results prove the hypothesis: imperfect IVF condition of fertilization jeopardize the expression DNMTs, Tets and imprinting status of imprinted genes for lipid metabolism regulation. Then it causes to abnormal expression of genes for lipid metabolism and regulation. This leads to the significant differences in lipid species quantification and lipid metabolism. So it contributed to low lipid transport efficiency, restricted fetal growth and LBW. This study provides a renewed knowledge of lipid metabolism in placenta and its relation to imprinted genes and gave some clinical aware for optimizing the ART practice.\n\nFundingThis work was supported by grants from the National Basic Research Program of China (973 Program) and National Natural Science Foundation of China.\n\nCompeting InterestsThe authors have declared that no competing interests exist.\n\nAbbreviations

Developmental Biology↗
bioRxiv2013

A model of flux regulation in the cholesterol biosynthesis pathway: Immune mediated graduated flux reduction versus statin-like led stepped flux reduction

Graphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=37 SRC=\"FIGDIR/small/000380_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (14K):\norg.highwire.dtl.DTLVardef@197f26org.highwire.dtl.DTLVardef@1eac3f3org.highwire.dtl.DTLVardef@1e698f1org.highwire.dtl.DTLVardef@42fb4b_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe model the cholesterol biosynthesis pathway and its regulation\nC_LIO_LIThe innate immune response leads to a suppression of flux through the pathway\nC_LIO_LIStatin inhibitors show a different mode of suppression to the immune response\nC_LIO_LIStatin inhibitor suppression is less robust and less specific than immune suppression\nC_LI\n\nAsbtractThe cholesterol biosynthesis pathway has recently been shown to play an important role in the innate immune response to viral infection with host protection occurring through a coordinate down regulation of the enzymes catalyzing each metabolic step. In contrast, statin based drugs, which form the principle pharmaceutical agents for decreasing the activity of this pathway, target a single enzyme. Here, we build an ordinary differential equation model of the cholesterol biosynthesis pathway in order to investigate how the two regulatory strategies impact upon the behaviour of the pathway. We employ a modest set of assumptions: that the pathway operates away from saturation, that each metabolite is involved in multiple cellular interactions and that mRNA levels reflect enzyme concentrations. Using data taken from primary bone marrow derived macrophage cells infected with murine cytomegalovirus infection or treated with IFN{gamma}, we show that, under these assumptions, coordinate down regulation of enzyme activity imparts a graduated reduction in flux along the pathway. In contrast, modelling a statin-like treatment that achieves the same degree of down-regulation in cholesterol production, we show that this delivers a step change in flux along the pathway. The graduated reduction mediated by physiological coordinate regulation of multiple enzymes supports a mechanism that allows a greater level of specificity, altering cholesterol levels with less impact upon interactions branching from the pathway, than pharmacological step reductions. We argue that coordinate regulation is likely to show a long-term evolutionary advantage over single enzyme regulation. Finally, the results from our models have implications for future pharmaceutical therapies intended to target cholesterol production with greater specificity and fewer off target effects, suggesting that this can be achieved by mimicking the coordinated down-regulation observed in immunological responses.

Systems Biology↗