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

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。

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.