孕晚期宫内高雄激素环境对SD子代雌鼠持续性低度炎症状态及胰岛素敏感性的影响  

Effect of intrauterine hyperandrogen exposure in late-gestation on chronic low-grade inflammation and insulin sensitivity in female SD offspring of rats

作　　者：黄媛 陈敏[2] 徐雯[1] 曹琦[1] 苏椿淋[1] 孙晓溪 Huang Yuan;Chen Min;Xu Wen;Cao Qi;Su Chunlin;Sun Xiaoxi(Department of Obstetrics and Gynecology,Hospital Affiliated to Fudan University,Shanghai 200011,China;Reproductive Center,Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Shanghai JiAi Genetics&IVF Institute,Obstetrics&Gynecology Hospital Affiliated to Fudan University,Shanghai 200011,China)

机构地区：[1]复旦大学附属妇产科医院,上海200032 [2]上海市交通大学医学院附属仁济医院生殖中心,200127 [3]复旦大学附属妇产科医院,上海集爱遗传与不育诊疗中心,200011

出　　处：《中华生殖与避孕杂志》2021年第8期747-753,共7页Chinese Journal of Reproduction and Contraception

基　　金：国家自然科学基金(81701409);上海市自然科学基金(12ZR441400)。

摘　　要：目的:动态观察孕晚期宫内高雄激素环境下子代SD雌性大鼠新生期、青春期、成年期的体质量、体脂分布、持续性低度炎症状态及胰岛素敏感性。方法:通过对妊娠18~20 d SD孕鼠皮下注射2 mg睾酮获取孕晚期宫内高浓度睾酮组(简称宫内高雄组)的子代雌鼠(n=15),并以等体积生理盐水皮下注射孕晚期SD孕鼠获取子代雌鼠为对照组(n=15),观察新生期(4 d)、青春期(15 d)、成年期(35 d)子代雌鼠的体质量、体脂体质量比;酶联免疫吸附法检测各时期子代雌鼠肿瘤坏死因子(tumor necrosis factor,TNF)-α、单核细胞趋化因子(monocyte chemotactic factor,MCP)-1的浓度;荧光染色方法检测腹膜脂肪组织中CD16的表达情况;取青春期、成年期子代雌鼠行腹腔注射葡萄糖耐受试验(intraperitoneal glucose tolerance test,IGTT)。结果:①宫内高雄组子代雌鼠新生期、青春期的体质量[(101.17±9.19)g、(211.61±11.94)g]高于对照组[(71.59±7.56)g,P<0.001;(189.85±6.97)g,P=0.003],体脂体质量比(0.16±0.18、0.27±0.20)高于对照组(0.11±0.17,P=0.002;0.21±0.18,P=0.006),而成年期子代雌鼠与对照组差异无统计学意义(P>0.05)。②宫内高雄组子代雌鼠不同时期(新生期、青春期、成年期)的体脂肌肉比(0.05±0.04、0.08±0.05、0.12±0.04)均高于对照组(0.08±0.05、0.13±0.07、0.18±0.06),差异均有统计学意义(P=0.031、P=0.007,P=0.005)。③宫内高雄组子代雌鼠各时期血清中TNF-α含量及MCP-1含量较对照组均显著增加(P<0.001,P=0.004);且腹膜脂肪组织中CD16表达较对照组明显增加(P=0.018,P=0.031,P=0.004)。④宫内高雄组青春期IGTT中120 min血糖[(165.00±58.68)mg/dL]明显高于对照组[(123.90±65.16)mg/dL,P=0.028],成年期的60 min[(189.73±69.87)mg/dL]、120 min血糖[(136.67±37.14)mg/dL]明显高于对照组[(170.18±32.66)mg/dL、(102.56±12.27)mg/dL](P=0.035、P=0.008)。结论:孕晚期宫内高雄激素环境可导致子代雌鼠新生期、青春期雄激�Objective To observe the weight,fat distribution,pesistent low-grade inflammation and insulin sensitivity of SD female rats in neonatal,adolescent and adult periods,which were exposed with intrauterine high androgen.Methods Fifteen offspring female rats which were exposed to high level of intrauterine testosterone in late pregnancy were obtained by subcutaneous injection of 2 mg testosterone into pregnant SD rats at 18-20 d of gestation.They were ascribed to the intrauterine testosterone group.At the same time,fifteen female offspring obtained from the pregnant SD rats injected with the same volume saline were as control group.The weight and body fat content were observed in neonatal stage(4 d),adolescent stage(15 d)and adult stage(35 d)of offspring female rats.Tumor necrosis factor(TNF)-αand monocyte chemotactic factor(MCP)-1 were tested by enzyme-linked immunosorbent assay(ELISA).The expression of CD16 in peritoneal adipose tissue was detected by immune fluorescence staining.Intraperitoneal glucose tolerance test(IGTT)was performed in adolescent and adult female rats.Results 1)The weight of neonatal and adolescent female offspring in intrauterine testosterone group were significantly increased compared with control group[(101.17±9.19)g vs.(71.59±7.56)g,P<0.001;(211.61±11.94)g vs.(189.85±6.97)g,P=0.003].Similarly,there was a significant difference in the ratio of fat and weight between the two groups(0.16±0.18 vs.0.11±0.17,P=0.002;0.27±0.18 vs.0.21±0.18,P=0.006),while there were no obvious significance in adult offspring between the two groups(P>0.05).2)The body fat and muscle ratio of female offspring in intrauterine testosterone group were higher than those in control group during neonatal,adolescent and adult periods(0.05±0.04 vs.0.08±0.05,P=0.031;0.08±0.05 vs.0.13±0.07,P=0.007;0.12±0.04 vs.0.18±0.06,P=0.005).3)The serum TNF-αand MCP-1 levels in intrauterine testosterone group were higher than those in control group(P<0.001,P=0.004),and the expression of CD16 in peritoneal adipose tissue was s

关 键 词：宫内高雄激素环境 子代 持续低度炎症 胰岛素敏感性 

分 类 号：R714[医药卫生—妇产科学]