上海交通大学学报(医学版) ›› 2023, Vol. 43 ›› Issue (4): 397-405.doi: 10.3969/j.issn.1674-8115.2023.04.001

• 论著 · 基础研究 •    

高脂饮食孕鼠胎盘微环境特征及其意义

徐一丹1(), 张骞仁1, 卢星宇1, 董艳1,2()   

  1. 1.上海交通大学医学院附属新华医院内分泌科,上海 200092
    2.上海市儿科医学研究所,上海 200092
  • 收稿日期:2023-02-14 接受日期:2023-03-09 出版日期:2023-04-28 发布日期:2023-04-28
  • 通讯作者: 董艳 E-mail:13862305195@163.com;dongyansh@sjtu.edu.cn
  • 作者简介:徐一丹(1997—),女,硕士生;电子信箱:13862305195@163.com
  • 基金资助:
    国家重点研发计划(2018YFC1004604);上海市科学技术委员会科研基金资助项目(18ZR1431100)

Effect of maternal high-fat diet on placental phenotype in mice

XU Yidan1(), ZHANG Qianren1, LU Xingyu1, DONG Yan1,2()   

  1. 1.Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
    2.Shanghai Institute of Pediatrics, Shanghai 200092, China
  • Received:2023-02-14 Accepted:2023-03-09 Online:2023-04-28 Published:2023-04-28
  • Contact: DONG Yan E-mail:13862305195@163.com;dongyansh@sjtu.edu.cn
  • Supported by:
    National Key Research and Development Program(2018YFC1004604);Scientific Reasearch Fund of Shanghai Science and Technology Commission(18ZR1431100)

摘要:

目的·通过分析高脂饮食对孕鼠胎盘微环境的影响,探讨胎盘微环境改变在母子代际传递中的作用。方法·3周龄C57BL/6J雌性小鼠在适应环境1周后随机分为2组,分别给予高脂饲料(高脂饮食组,HFD组)和普通饲料(对照饮食组,CD组),5周后分别与正常饲喂雄鼠交配怀孕,2组孕鼠按照原饲料继续喂养至孕20 d。于孕20 d时收集母鼠胎盘、肝脏和胎鼠肝脏组织,通过苏木精-伊红染色(hematoxylin-eosin staining,H-E染色)、免疫组织化学(免疫组化)染色、Western blotting以及反转录聚合酶链反应(RT-PCR)等方法观察母鼠高脂饮食对胎盘炎症状态和胎盘结构的影响;检测胎鼠肝脏组织脂质沉积水平;检测子鼠3周龄断乳时的体质量、空腹血糖和腹腔注射葡萄糖糖耐量检测水平。结果·经孕前与孕期饮食干预后,HFD组母鼠体质量增加,肝脏三酰甘油(triacylglycerol,TAG)和总胆固醇(total cholesterol,TC)水平均明显高于CD组母鼠,差异有统计学意义(均P<0.05)。与CD组相比,HFD组胎鼠肝组织可见大小不等的脂性空泡,肝细胞出现脂肪变性,肝脏TAG水平上升,但差异无统计学意义(P>0.05);HFD组子鼠3周龄时体质量明显升高,空腹血糖水平升高,葡萄糖耐量试验曲线下面积增加(均P<0.05);免疫组化结果显示HFD组母鼠胎盘内白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)水平明显增加(均P<0.05),而IL-1β水平无明显变化;H-E染色显示HFD组胎盘迷路区(母胎交换区)面积占比明显减少,通过ImageJ软件统计2组差异具有统计学意义(P<0.05),并且血管间膜增厚,母体血窦狭小;RT-PCR结果显示HFD组胎盘紧密连接相关蛋白Zo-1(zonula occludens 1)和claudin的表达增加,差异有统计学意义(均P<0.05)。结论·母代高脂饮食可引起胎盘炎症因子水平增加和胎盘结构异常,这些改变可能与子代糖脂代谢紊乱有关。

关键词: 高脂饮食, 胎盘, 滋养层细胞, 母子代际传递

Abstract:

Objective ·To analyze the effects of maternal high-fat diet on placental phenotype, and investigate the role of placental microenvironment in the intergenerational transmission. Methods ·The 3-week-old C57BL/6J female mice were fed with either the high-fat diet (HFD group) or the control diet (CD group) for 5 weeks before mating and throughout gestation. Placentas and fetal liver tissues were collected from maternal mice after 20 d of gestation. The effects of maternal HFD on the placental inflammation and placental structure were investigated by hematoxylin-eosin staining (H-E staining), immunohistochemistry, Western blotting and RT-PCR. The lipid deposition levels in fetal livers were also detected. Body weight changes, fasting blood glucose and glucose tolerance levels of the 3-week-old weaned mice were also detected. Results ·The body weight of female mice in the HFD group increased significantly, and the liver triacylglycerol (TAG) and total cholesterol (TC) levels were higher than those in the CD group (all P<0.05). Compared to the CD group, the liver cells of fetus in the HFD group showed steatosis, lipid vacuoles of different sizes, and the content of TAG in the fetal livers in the HFD group increased, but the difference was not statistically significant (P>0.05). Compared to the CD group, the body weight, fasting blood glucose level and the area under the glucose tolerance curve of the 3-week-old weaned mice of the HFD group were increased significantly (all P<0.05). The immunohistochemical results showed that the levels of interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the placenta in the HFD group were significantly increased (both P<0.05), and the level of IL-1β did not change significantly. In addition, H-E staining of placentas showed that the area proportion of the labyrinth zone (the maternal-fetal exchange area) in the HFD group decreased significantly, which was statistically significant by ImageJ software (P<0.05). The intervascular membrane thickened, and the maternal blood sinuses were narrow. RT-PCR results showed the expressions of placental tight-junction-related protein Zo-1 (zonula occludens 1) and claudin were increased (both P<0.05). Conclusion ·Maternal high-fat diet may result in placental inflammation and abnormal structure, which may be related to glucose and lipid metabolism disorder in offspring.

Key words: maternal high-fat diet, placenta, trophoblast cell, intergenerational transmission

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