Cytokines' role, especially G-CSF and IL-6, on human ovarian function and its clinical application

细胞因子尤其是G-CSF和IL-6对人卵巢功能的影响及其临床应用

• 批准号: 17591762
• 负责人: MAKINODA Satoru
• 金额: $ 2.31万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591762/
• 关键词: Ovarian function; luteal regression, cytokine; cytokine; G-CSF; IL-6; Real-time quantitative RT-PCR; ovulation induction; clinical trial; IL6

We have revealed the effects of cytokines, especially G-CSF and IL-6 on ovarian function as follows.1) Cyclic changes of cytokines during the normal menstrual cycleThe cyclic changes of the cytokines▲(TNF-α, IL-1β, IL-6, GM-CSF, M-CSF) in serum that were already reported to be involved in the mechanism of ovulation and G-CSF were measured during the normal menstrual cycle. Only G-CSF showed a significant increase a few days before ovulation. Although it was not significant, IL-6 showed an increase during the late luteal phase.2) Cyclic changes of IL-6 at the human follicular wall and its relation to the luteal regressionThe expression of IL-6 mRNA at the human follicular wall increased significantly in the regressing corpus luteum. Moreover, increased IL-6 protein and receptor were observed in the follicular wall of the late luteal phase. These results will contribute to elucidate the mechanism of luteal insufficiency.3) Clinical trial to use G-CSF as a supportive drug to ovulation inductionThe following clinical trials were conducted to induce ovulation in the patients of luteinized unruptured follicle (LUF). The patients who showed LUF at the last Clomiphene-hCG cycle participated in this clinical trial. Ovulation induction using Clomiphene-hCG was performed as the last cycle. In addition, G-CSF 100 μg was administered 24-48 hours before hCG. The ovulation was successfully induced at the rate of 87.1% (54/62). Since the ovulation rate of the patients before this clinical trial was 53.5 %, the rate is significantly high (p<0.01).Our results established a new method to induce ovulation using G-CSF.

我们揭示了细胞因子，特别是G-CSF和IL-6对卵巢功能的影响如下。1)正常月经周期中细胞因子的周期变化测定血清中已报道参与排卵机制的细胞因子▲（TNF-α、IL-1β、IL-6、GM-CSF、M-CSF）和G-CSF在正常月经周期中的周期变化。只有G-CSF在排卵前几天明显升高。虽然不明显，但IL-6在黄体晚期出现升高。2)人卵泡壁IL-6的循环变化及其与黄体退化的关系黄体退化后，人卵泡壁IL-6 mRNA的表达显著升高。黄体晚期卵泡壁IL-6蛋白和受体升高。这些结果将有助于阐明黄体功能不全的机制。3) G-CSF作为促排卵辅助药物的临床试验以下是对未破裂卵泡黄体化（LUF）患者进行促排卵的临床试验。在最后一个克罗米芬- hcg周期出现LUF的患者参加了本临床试验。最后一个周期使用克罗米芬促排卵。另外，在hCG前24-48小时给予G-CSF 100 μg。诱导排卵成功率为87.1%（54/62）。由于本临床试验前患者的排卵率为53.5%，因此排卵率显著高（p<0.01）。本研究建立了一种利用G-CSF诱导排卵的新方法。

项目成果

Possible involvement of interleukin-6 in human luteolysis

IL-6 可能参与人类黄体溶解

• 发表时间: 2007
• 作者: Shoko Morishima;Masahide Omchi;Tsuneto Keji;Nishiyama Koji;Hiroyuki Yamaguchi;Masanori Kanemura;Yoshito Terai;Masa-Aki Shibata;Yoshinori Otsuki;大槻 勝紀;Yoshinori Otsuki;Makinoda S;Makinoda S;牧野田 知;Negishi H;Negishi H;Dahm-Kahler P;広崎 奈津子;Dahm-Kahler P;Makinoda S;牧野田 知;牧野田 知;Makinoda S;Fujii R;藤井 亮太;広崎 奈津子;Makinoda S;Fujii R
• 通讯作者: Fujii R

Ovarian blood flow measurement and its clinical application Medicine and Gynecology

卵巢血流测量及其临床应用 医学妇科

• 发表时间: 2007
• 作者: Shoko Morishima;Masahide Omchi;Tsuneto Keji;Nishiyama Koji;Hiroyuki Yamaguchi;Masanori Kanemura;Yoshito Terai;Masa-Aki Shibata;Yoshinori Otsuki;大槻 勝紀;Yoshinori Otsuki;Makinoda S;Makinoda S;牧野田 知;Negishi H;Negishi H;Dahm-Kahler P;広崎 奈津子;Dahm-Kahler P;Makinoda S;牧野田 知;牧野田 知;Makinoda S;Fujii R;藤井 亮太;広崎 奈津子;Makinoda S;Fujii R;広崎 奈津子;藤井 亮太;広崎 奈津子;Fujii R;Makinoda S
• 通讯作者: Makinoda S

An intravital microscopy method permitting continuous long-term observations of ovulation in vivo in the rabbit

• DOI: 10.1093/humrep/dei394
• 发表时间: 2006-03-01
• 期刊: HUMAN REPRODUCTION
• 影响因子: 6.1
• 作者: Dahm-Kähler, P;Löfman, C;Brännström, M
• 通讯作者: Brännström, M

Regulation of amphiregulin, EGFR‐like factor expression by hCG in cultured human granulosa cells

• DOI: 10.1080/00016340701314959
• 发表时间: 2007-06
• 期刊: Acta Obstetricia et Gynecologica Scandinavica
• 影响因子: 4.3
• 作者: Hiroaki Negishi;Chiaki Ikeda;Yoko Nagai;Akiko Satoh;Yoko Kumasako;Satoru Makinoda;Takafumi Ustunomiya

黄体化未破裂卵胞(LUF)に対する排卵誘発補助薬としてのG-CSFの有用性

G-CSF 作为黄素化未破裂卵泡 (LUF) 促排卵佐剂的用途

• 发表时间: 2007
• 作者: Shoko Morishima;Masahide Omchi;Tsuneto Keji;Nishiyama Koji;Hiroyuki Yamaguchi;Masanori Kanemura;Yoshito Terai;Masa-Aki Shibata;Yoshinori Otsuki;大槻 勝紀;Yoshinori Otsuki;Makinoda S;Makinoda S;牧野田 知;Negishi H;Negishi H;Dahm-Kahler P;広崎 奈津子;Dahm-Kahler P;Makinoda S;牧野田 知;牧野田 知;Makinoda S;Fujii R;藤井 亮太;広崎 奈津子
• 通讯作者: 広崎 奈津子