The presence of midkine and its possible implication in human ovarian follicles

The presence of midkine and its possible implication in human ovarian follicles
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DOI:
10.1111/j.1600-0897.2007.00522.x
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发表时间:
2007-10-01
影响因子:
3.6
通讯作者:
Taketani, Yuji
Taketani, Yuji
中科院分区:
医学3区
文献类型:
--
作者:
Hirota, Yasushi;Osuga, Yutaka;Taketani, Yuji

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问题:卵泡发生动态变化以提供成熟的卵子,这个过程涉及血管生成、卵泡细胞增殖和白细胞募集。中期因子(Midkine,MK)是一种肝素结合生长因子,具有血管生成、有丝分裂和趋化活性。在本研究中,我们研究了MK在人卵巢卵泡中的存在及其可能的作用。研究方法:从体外受精和胚胎移植的妇女采集卵泡液(FF)和黄素化颗粒细胞(LGC)。免疫印迹法检测FFMK蛋白的表达。测定卵泡灌洗液中MK、雌二醇和氧的浓度。5-溴-2‘-脱氧尿苷(BrdU)掺入法测定LGC。手术获取正常卵巢组织,进行MK mRNAs原位杂交。结果:正常卵巢组织中存在MK蛋白。MK基因在大卵泡的颗粒细胞和膜细胞均有表达。FF中MK浓度与氧气浓度呈显著负相关,MK浓度与雌二醇浓度呈显著正相关。结论:低氧状态是卵泡生长的特征之一,低氧状态与MK的产生有关。鉴于MK参与了卵泡发育中颗粒细胞的增殖和雌二醇的产生,MK可能在人的卵巢中起到局部调节的作用。
Problem:Ovarian follicles undergo a dynamic change to provide a mature ovum, and the process involves angiogenesis, follicular cell proliferation and leukocyte recruitment. Midkine (MK) is a heparin-binding growth factor that has angiogenic, mitogenic, and chemotactic activities. In the present study, we investigated the presence of MK and its possible role in human ovarian follicles.Method of study:Follicular fluid (FF) and luteinized granulosa cells (LGC) were collected from women undergoing in vitro fertilization and embryo transfer. Expression of MK protein in FF was examined by Western blotting. Concentrations of MK, estradiol and oxygen in FF were measured. 5-bromo-2'-deoxyuridine (BrdU) incorporation assay was performed in LGC. Normal ovarian tissues were obtained surgically and used in in-situ hybridization of MK mRNA.Results:The presence of MK protein was verified in FF. MK mRNA was expressed in both granulosa cells and theca cells of large follicles. There is a significant negative correlation between the concentrations of MK and oxygen in FF, and a significant positive correlation between the concentrations of MK and estradiol. MK promoted BrdU uptake in LGC.Conclusion:The present findings imply that hypoxic condition, a characteristic of growing follicles, associates with the production of MK. Given that MK is involved in granulosa cell proliferation and estradiol production in developing follicles, MK may play a role as a local regulator in the human ovary.