国际生殖健康/计划生育 ›› 2015, Vol. 34 ›› Issue (3): 189-192.

• 论著 • 上一篇    下一篇

邻苯二甲酸单乙基己基酯抑制人卵巢黄素化颗粒细胞激素合成机制的研究

蔡晓辉,石程,沈浣   

  1. 100050 首都医科大学附属北京友谊医院妇产科(蔡晓辉);北京大学人民医院计划生育与生殖医学科(石程,沈浣)
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2015-05-15 发布日期:2015-05-15
  • 通讯作者: 沈浣

Effect of Mono-(2-ethylhexyl) Phthalate on Steroidogenesis in Human Granulosa Cells

CAI Xiao-hui,SHI Cheng,SHEN Huan.   

  1. Department of Obstetrics and Gynecology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China(CAI Xiao-hui);Department of Family Planning and Reproductive Medicine,Peking University People′s Hospital,Beijing 100044,China(SHI Cheng,SHEN Huan)
  • Received:1900-01-01 Revised:1900-01-01 Published:2015-05-15 Online:2015-05-15
  • Contact: SHEN Huan

摘要: 目的:研究邻苯二甲酸单乙基己基酯[Mono-(2-ethylhexyl)phthalate,MEHP]抑制人卵巢黄素化颗粒细胞激素合成的机制。方法:选取在北京大学人民医院行体外受精-胚胎移植的患者6例,分别收集卵泡液,提取颗粒细胞进行原代体外培养72 h后,分别加入MEHP 25,300,500 μmol/L,并于之后48 h通过实时聚合酶链反应(real-time PCR)检测胆固醇侧链裂解酶(CYP11A1)、过氧化物酶体激活受体γ(peroxisome proliferator-activated receptor,PPAR-γ)、芳香化酶基因(CYP19A1)、3β-羟基类固醇脱氢酶(3β-HSD)的表达。结果:MEHP为300及500 μmol/L时CYP19A1的表达均明显降低(P<0.05);500 μmol/L的MEHP可使CYP11A1表达明显降低(P<0.05);当MEHP为500 μmol/L时3β-HSD的表达明显降低(P<0.05);当MEHP达到300,500 μmol/L时,PPAR-γ的表达明显增加(P<0.05)。结论:MEHP不仅能降低雌激素合成关键酶CYP19A1的合成,也抑制了孕激素合成关键酶CYP11A1及3β-HSD的合成。此外,MEHP能促进PPAR-γ的生成。

关键词: 苯二甲酸类, 生殖细胞, 雌激素类, 孕激素类

Abstract: Objective: To investigate the toxic effect of mono-(2-ethylhexyl) phthalate(MEHP) on steroidogenesis in human granulosa cells(GCs). Methods:Follicular fluid were collected from six patients undergoing in vitro fertilization. GCs were extracted and cultured in vitro for 72 hours, and then treated with MEHP (25,300,500 μmol/L). After treatment for 48 hours,the expression levels of CYP11A1,PPAR-γ,CYP19A1 and 3β-HSD mRNAs were determined by real-time PCR. Results:The expression of CYP19A1 mRNA in GCs was significantly down-regulated by MEHP treatment of 300 μmol/L and 500 μmol/L(P<0.05), and the expression of CYP11A1 was significantly down-regulated by MEHP treatment of 500 μmol/L(P<0.05). Also, the expression of 3β-HSD mRNA was decreased by 500 μmol/L MEHP treatment(P<0.05), while PPAR-γ expression was increased by 300 μmol/L and 500 μmol/L MEHP treatment(P<0.05). Conclusions:MEHP at higher doses affects steroidogenesis in GCs by down-regulating the expressions of steroid biosynthesis enzymes CYP19A1,CYP11A1 and 3β-HSD, and by up-regulating the expression of PPAR-γ.

Key words: Phthalic acids, Germ cells, Estrogens, Progestins