妊娠早期高雌激素暴露对小鼠子代体重及胎盘的影响

Effects of high estrogen exposure in early pregnancy on body weight and placenta of mouse offspring

目的 探讨妊娠早期高雌激素暴露对小鼠子代体重、胎盘结构及功能表达的影响。方法 购入小鼠进行1周适应性喂养,选择自然发情雌鼠与正常雄鼠交配,按随机数字表法将其分为对照组(NC组)和高雌激素组(EV100组),每组各7只。EV100组在妊娠后第5.5~12.5天每日上午9:00给予口服溶于玉米油的戊酸雌二醇(100μg·kg·d),NC组给予相同体积的玉米油。建模成功后,于妊娠14.5天取胎鼠和胎盘称重,采用HE染色和PAS染色比较小鼠胎盘结构变化。采用Luminex液相悬浮芯片技术检测胎盘相关细胞因子的表达变化。结果 EV100组小鼠的子代体重、胎盘重量和胎盘效率均明显低于NC组,差异有统计学意义(t值分别是4.932、2.639、2.336,P<0.05)。HE染色和PAS染色均显示EV100组小鼠胎盘迷路区占胎盘总面积的比例较NC组减少,差异有统计学意义(t值分别是3.819、4.800,P<0.05)。EV100组小鼠的胎盘基质金属蛋白酶-2和胰岛素样生长因子-1表达水平明显比NC组低,差异有统计学意义(t值分别是12.270、15.630,P<0.05)。结论 妊娠早期高雌激素暴露可导致小鼠子代体重和胎盘重量降低,胎盘结构改变,这可能与胎盘生长相关细胞因子表达水平降低有关。

Objective To investigate the effects of high estrogen exposure in early pregnancy on offspring weight, placental structure and functional expression in mice.Methods Mice were purchased for adaptive feeding for 1 week.Natural estrus female mice were selected to mate with normal male mice, and then they were divided into control group(NC group) and high estrogen group(EV100 group) according to random number table method with 7 mice in each group.EV100 group was given oral estradiol valerate(100 μg·kg·d) dissolved in corn oil at 9:00 a.m.daily on 5.5~12.5 days after pregnancy, NC group was given the same volume of corn oil.After the successful modeling, the fetal mice and placenta were weighed at 14.5 days of gestation, and the placenta structure changes were compared by HE staining and PAS staining.The expression of placental cytokines was detected by Luminex liquid suspension chip technology.Results The offspring weight, placental weight and placental efficiency of EV100 group were significantly lower than those in NC group, and the differences were statistically significant(t=4.932,2.639 and 2.336,respectively, P<0.05).HE staining and PAS staining showed that the proportion of the placental labyrinth to the total placenta in EV100 group was lower than that in NC group, and the difference was statistically significant(t=3.819 and 4.800,respectively, P<0.05).The expression levels of placental matrix metalloproteinase-2 and insulin-like growth factor-1 in EV100 group were significantly lower than those in NC group, and the difference was statistically significant(t=12.270 and 15.630,respectively, P<0.05).Conclusion High estrogen exposure in early pregnancy results in reduced birth weight and placental weight in mice, as well as changes in placental structure, which may be associated with decreased expression levels of placental growth-related cytokines.