低出生体重和表观遗传异常是ART子代的二大健康风险，这与"胚胎/胎儿源性的成年心血管疾病"的出生儿病理改变相同。课题组因此建立小鼠模型，在观察到老年ART小鼠血脂指标改变同时，发现肝组织胆固醇和脂肪酸合成代谢调节通路：胰岛素诱导基因-类固醇调节元件结合蛋白-及其裂解激活蛋白（INSIG- SREBP-SCAP）基因表达显著改变。故此，拟在上述研究基础上，渐次进行ART老年小鼠肝组织INSIG -SREBP-SCAP通路基因调节区甲基化修饰，新生、性成熟和中年小鼠相关基因表达修饰动态变化，以及小鼠卵母细胞、胚胎相关基因表达研究，探索ART小鼠INSIG-SREBP-SCAP通路基因表达改变发生发展的机理，分析ART过程可能的作用环节和时间点，为ART子代成年血脂代谢异常风险评估和ART技术可能的改进途径提供科学依据。

Since Louise Brown was born by in vitro fertilization and embryo-transfer (IVF-ET) in 1978, more than 4 million babies have been born using assisted reproductive technology (ART). Besides its successful application in solving many problems of human infertility, some negative effects on the developing conceptus have been found. Decreased birth weight and imprinting disorders are the two main potential risks for the health of ART children. The evidences already demonstrated that embryo/fetal changes in growth and epigenetic modification may predispose offspring to increased risk of metabolic and cardiovascular diseases in the adult life, or the concept of the embryo/fetal origins of adult diseases. Therefore, ART mouse models have been established in our research team. The abnormal adipose metabolism and increased level of serum cholesterol and altered hepatic expression of the key transcription factors for cholesterol homeostasis, insulin-induced gene (INSIG), sterol regulatory element binding proteins (SREBPs) and SREBP cleavage-activating protein (SCAP) were observed in the aged ART mice. For the further investing the underlying molecular mechanisms, we plan to measure the methylation rates of the differentiate methylation regions of INSIG-SREBP-SCAP in the liver of aged mice conceived from IVF, intracytoplasmic injection (ICSI), in vitro oocyte maturation (IVM) and in vivo fertilization (control). Followed by analyses of the expression and/or methylation situations of INSIG-SREBP-SCAP in ART mice at middle-age (7 months) and sexual maturity (8 weeks), new-birth, or preimplantation embryos and oocytes, the effects of the main factors and key time point of ART procedures on the metabolism of serum cholesterol and the hepatic expression of INSIG-SREBP-SCAP will be studied.