The role of macrophage colony-stimulating factor (M-CSF) on folliculogenesis and ovulation and its clinical application

巨噬细胞集落刺激因子（M-CSF）对卵泡发生和排卵的作用及其临床应用

• 批准号: 13671731
• 负责人: TANAKA Nobuyuki
• 金额: $ 2.05万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671731/
• 关键词: folliculogenesis; ovulation; M-CSF; poor responder; poor-responder

We previously reported that macrophage colony-stimulating factor (M-CSF) and/or macrophages are involved in folliculogenesis and promote ovulation in eCG/hCG-primed immature rats and osteopetrotic (op/op) mutant mice. In this study, we clinically investigated M-CSF concentrations in serum and follicular fluid through IVF-ET cycles, and the effectiveness of M-CSF on poor ovarian responders to hMG. Serum M-CSF concentration was gradually increased throughout the cycle, and reached a peak around the day of oocyte retrieval, while no significant change of M-CSF concentration was observed in cases of poor ovarian response to hMG. The M-CSF (8 X 10^6 IU/day) was administered intravenously 3 or 7 times to 13 poor responders (16 cycles), who had shown no or poor follicular development at previous hMG cycles. They were categorized as "normal", "subnormal", and "negative" group according to the results of the clonidine test. In 4 of 5 cycles in "normal" group and 2 of 5 cycles in "subnormal" group, multiple dominant follicles were successfully achieved with adequate estradiol and progesterone levels. However, no multiple dominant follicles were observed in "negative" group. The results suggested that the ovarian production of M-CSF in response to gonadotropins may be impaired in poor responders, and demonstrated that the supplementary M-CSF administration can improve the follicular development on clonidine-positive ("normal" and "subnormal") poor ovarian responders.

我们先前报道了巨噬细胞集落刺激因子(M-CSF)和/或巨噬细胞参与了心电/人绒毛膜促性腺激素(CG/hCG)诱导的未成熟大鼠和骨质疏松(OP/OP)突变小鼠的卵泡形成和排卵。在这项研究中，我们通过IVF-ET周期临床研究了血清和卵泡液中M-CSF的浓度，以及M-CSF对HMG反应差的卵巢患者的疗效。血清M-CSF浓度在整个周期内逐渐升高，并在取卵当天达到高峰，而卵巢对HMG反应差的患者血清M-CSF浓度变化不明显。对13例(16个周期)卵泡发育不良的患者，给予M-CSF(8×10~(-6)IU/d)静脉注射3~7次。根据可乐定试验结果分为“正常”组、“亚正常”组和“阴性”组。在“正常”组的5个周期中有4个周期和“低于正常”组的5个周期中的2个周期成功地获得了多个优势卵泡，且雌二醇和孕酮水平充足。而“阴性”组未见多个优势卵泡。结果提示，对促性腺激素反应差的患者，卵巢对M-CSF的反应可能受到抑制，补充M-CSF可促进可乐定阳性(“正常”和“异常”)卵巢反应不良患者的卵泡发育。

项目成果

N. Tanaka, K. Nishimura, K. Matsuura, H. Okamura: "Supplementary macrophage colony-stimulating factor (M-CSF) treatment on poor ovarian responders to gonadotropins"Frontiers in Endocrinology. 21. 43-49 (1999)

N. Tanaka、K. Nishimura、K. Matsuura、H. Okamura：“补充巨噬细胞集落刺激因子 (M-CSF) 对促性腺激素卵巢反应不良者的治疗”内分泌学前沿。

田中信幸: "卵胞発育から排卵過程におけるCSF-1の役割"産科と婦人科. 67. 574-580 (2000)

Nobuyuki Tanaka：“CSF-1 从卵泡发育到排卵过程的作用”妇产科 67. 574-580 (2000)。

N.Tanaka: "Supplementary macrophage colony-stimulating factor (M-CSF) treatment on poor ovarian responders to gonadotropins"Frontiers in Endocrinology. 21. 43-49 (1999)

N.Tanaka：“补充巨噬细胞集落刺激因子（M-CSF）治疗卵巢对促性腺激素反应不佳的患者”内分泌学前沿。

Y. Okamura, A. Miyamoto, N. Manabe, N. Tanaka, H. Okamura, M. Fukumoto: "Protein tyrosine kinase expression in the porcine ovary"Molecular Human Reproduction. 7. 723-729 (2001)

Y. Okamura、A. Miyamoto、N. Manabe、N. Tanaka、H. Okamura、M. Fukumoto：“猪卵巢中的蛋白酪氨酸激酶表达”人类分子生殖。

Y.Okamura: "Protein tyrosine kinase expression in the porcine ovary"Molecular Human Reproduction. 7. 723-729 (2001)

Y.Okamura：“猪卵巢中的蛋白酪氨酸激酶表达”《分子人类生殖》。