发育相关印记基因表观遗传学改变介导孕期PEs暴露与妊娠结局

Plant estrogen (PEs) is a chemical with weak estrogen effect. It has been demonstrated that PEs can pass through the placental barrier, cause endocrine balance reproductive barriers and Tumor initiation. Current research in Pregnancy exposure of PEs on health effects and their offspring are poorly understood, the existing research only focuses on the isoflavone PEs, but for other types of research is very scarce and results are controversial. Our studies showed that pregnant rats intrauterine of PEs exposure, can cause the offspring imprinted genes of CDKN1C and methyltransferase DNMT1 expression level affected; other data showed prenatal PEs exposure can increase low birth weight and gestational age of offspring of birth outcomes. Current studies based birth cohort in the large-scale population in Guangxi area has been started on the 8 kinds of commonly PEs selection, 300-500 cases of birth cohort populations whose environmental PEs exposure during pregnancy. The Effects on offspring growth and development of adverse outcome of fetal epigenetic effects and related imprinted genes methylation were studied, combination of pregnant rats and on cellular model which PEs exposure on offspring birth defects, cell imprinting gene methylation and serum metabolic profiling changes were also studied in current project, our aim is to clarify the mechanism of the long-term effect of prenatal exposure to PEs.

植物性雌激素（PEs）是植物中具有诱导弱雌激素作用的化学物质。PEs作为一种内分泌干扰物，可能引起不孕等妊娠缺陷及对雌激素敏感器官肿瘤增加的风险。目前孕期PEs暴露对孕妇及子代的健康影响的研究甚少，结果有争议，已有研究也仅关注异黄酮类PEs，而对其他种类研究十分匮乏。本课题前期研究发现，怀孕大鼠宫内PEs暴露可影响子鼠印记基因CDKN1C及甲基化转移酶DNMT1的表达；也有孕期PEs暴露增加子代低体重和小于胎龄儿发生率等出生不良结局的报道。本课题拟在广西地区大规模人群出生队列调查基础上，选择常见的PEs，对300-500例出生队列人群进行孕期PEs暴露子代不良结局影响及胎儿生长发育相关印记基因表观遗传学等研究；结合怀孕大鼠及细胞模型对PEs暴露子代出生缺陷、细胞印记基因甲基化及血清代谢图谱改变等影响进行研究，阐明相关印记基因表观遗传学改变介导孕期PEs暴露对妊娠结局影响的作用机制。

植物性雌激素（PEs）是植物中具有诱导弱雌激素作用的化学物质，在体内可能引起不孕等妊娠缺陷及对雌激素敏感器官肿瘤增加的风险。目前孕期PEs暴露对孕妇及子代的健康影响的研究甚少，结果有争议。本课题在前期对桂林、柳州孕期妇女人群调查资料收集、整理基础上，分析了孕期妇女体内PEs暴露水平与子代出生结局的关联性，进行了实验室孕鼠早期PEs暴露对子代胎龄、出生体重、身长等结局的影响和PEs对实验室体外培养鼠胚原代细胞、乳腺癌细胞生物性行为改变及其相关基因表达等的影响进行研究探讨。

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