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高卵巢反应对体外受精女性种植窗期子宫内膜中内分泌腺源性血管内皮生长因子(EG-VEGF)表达的影响。

Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women.

作者信息

Xu Li-Zhen, Gao Min-Zhi, Yao Li-Hua, Liang A-Juan, Zhao Xiao-Ming, Sun Zhao-Gui

机构信息

Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University Jinan 250021, China ; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200135, China.

Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200135, China.

出版信息

Int J Clin Exp Pathol. 2015 Aug 1;8(8):8902-11. eCollection 2015.

Abstract

OBJECTIVE

To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER).

DESIGN

Prospective laboratory study.

SETTING

University hospital.

PATIENTS

Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL.

INTERVENTION(S): Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC.

MAIN OUTCOME MEASURE(S): Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry.

RESULTS

All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC.

CONCLUSION

Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles.

摘要

目的

探讨卵巢刺激对接受体外受精(IVF)女性种植窗期子宫内膜中内皮糖蛋白(EG-VEGF)mRNA和蛋白表达的影响及其与子宫内膜容受性(ER)的关系。

设计

前瞻性实验室研究。

地点

大学医院。

患者

18名处于促排卵周期(SC)的女性作为研究对象,18名处于自然周期(NC)的女性作为对照。SC组女性分为两个亚组,高卵巢反应组(SC1,n = 9),血清E2峰值>5000 pg/mL;中度卵巢反应组(SC2,n = 9),血清E2峰值为1000 - 5000 pg/mL。

干预措施

NC组在排卵后6天、SC组在取卵后进行子宫内膜活检。

主要观察指标

采用苏木精-伊红(HE)染色观察子宫内膜组织学分期。通过实时聚合酶链反应分析测定EG-VEGF mRNA表达水平,采用免疫组织化学法测定蛋白水平。

结果

所有子宫内膜样本均处于分泌期。SC1组子宫内膜发育比NC组提前1至2天,且腺上皮与间质组织不同步。免疫组织化学分析显示,EG-VEGF蛋白主要表达于腺上皮细胞和血管内皮细胞,也存在于间质中。图像分析证实,SC1组子宫内膜的腺上皮和间质中EG-VEGF蛋白表达均显著低于SC2组和NC组子宫内膜。此外,SC1组EG-VEGF mRNA水平显著低于NC组。SC2组与NC组的EG-VEGF蛋白和mRNA水平均无显著差异。

结论

种植窗期EG-VEGF表达降低与高卵巢反应有关,这可能是IVF周期中ER受损及种植率降低的原因。

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本文引用的文献

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[Prokineticins: new regulatory peptides in human reproduction].[促动力蛋白:人类生殖中的新型调节肽]
Med Sci (Paris). 2014 Mar;30(3):274-9. doi: 10.1051/medsci/20143003015. Epub 2014 Mar 31.
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Eleven golden rules of quantitative RT-PCR.定量逆转录聚合酶链反应的十一条黄金法则。
Plant Cell. 2008 Jul;20(7):1736-7. doi: 10.1105/tpc.108.061143. Epub 2008 Jul 29.

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