山东大学学报 (医学版) ›› 2020, Vol. 1 ›› Issue (7): 60-66.doi: 10.6040/j.issn.1671-7554.0.2020.0538
丁祥云1,于清梅1,张文芳2,庄园1,郝晶3
DING Xiangyun1, YU Qingmei1, ZHANG Wenfang2, ZHUANG Yuan1, HAO Jing3
摘要: 目的 检测胰岛素样生长因子II(IGF-II)在多囊卵巢综合征(PCOS)患者卵巢颗粒细胞中的表达水平及与促排卵结局的相关性。 方法 采用实时荧光定量PCR(qRT-PCR)检测42例 PCOS正常反应患者(PCOS正常反应组)、42例PCOS高反应患者(PCOS高反应组)及90例对照组(因输卵管或男方因素助孕者)颗粒细胞中IGF-II的表达,对比分析各组IGF-II的表达及促排卵相关参数的差异,并进行关联性分析。 结果 IGF-II在对照组、PCOS正常反应组和PCOS高反应组相对表达量的中位数分别为1.3(0.5~1.8)、1.7(1.4~2.2)及3.2(2.5~4.3),3组间比较差异有统计学意义(F=88.7, P<0.001),其中PCOS正常反应组和PCOS高反应组均高于对照组(P均<0.001),PCOS高反应组高于PCOS正常反应组(P<0.001)。在PCOS高反应组,注射人绒毛膜促性腺素(HCG)日雌二醇(E2)、直径≥14 mm的卵泡数、获卵数、2原核受精卵(2PN)数、优质胚胎数、卵裂数及可移植胚胎数均高于对照组及PCOS正常反应组,差异有统计学意义(P均<0.05),HCG日黄体生成素(LH)、获卵率、受精率及可利用卵子率均低于对照组和PCOS正常反应组(P均<0.05);在PCOS正常反应组,促性腺激素(Gn)总量(P=0.02)及E2值(P<0.001)均低于对照组。相关性分析结果显示,颗粒细胞上IGF-II的相对表达量与HCG日E2值(r=0.163, P=0.032)、HCG日≥14 mm的卵泡数(r=0.286, P<0.001)、2PN数(r=0.246, P<0.001)、卵裂数(r=0.296, P<0.001)、优质胚胎数(r=0.286, P<0.001)、获卵数(r=0.386, P<0.001)、可移植胚胎数(r=0.252, P<0.001)及优质胚胎率(r=0.155, P=0.041)呈正相关;多重线性回归分析结果显示,PCOS患者颗粒细胞上IGF-II的相对表达量与获卵数(β=0.921, P<0.001)及优质胚胎率(β=0.285, P<0.001)呈正相关,与卵裂数(β=-0.283, P<0.001)呈负相关。 结论 IGF-II在接受辅助生殖技术治疗的PCOS患者颗粒细胞中高表达,与获卵数及优质胚胎率密切相关,有促进卵泡和早期胚胎发育的潜能。
中图分类号:
[1] | Lizneva D, Suturina L, Walker W, et al. Criteria,prevalence,and phenotypes of polycystic ovary syndrome[J]. Fertil Steril, 2016, 106(1): 6-15. |
[2] | 乔杰, 齐新宇, 徐雅兰, 等. 关注影响女性健康的重要生殖内分泌疾病多囊卵巢综合征[J]. 中国实用妇科与产科杂志, 2020, 36(1): 1-9. |
[3] | Dunne C, Shan A, Nakhuda G, et al. Measurement of Luteinizing hormone level after gonadotropin releasing hormone agonist trigger is not useful for predicting oocyte maturity[J]. J Obstet Gynaecol Can, 2018, 40(12): 1618-1622. |
[4] | Oudshoorn SC, van Tilborg TC, Eijkemans MJC, et al. Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder[J]. Hum Reprod, 2017, 32(12): 2506-2514. |
[5] | 刘小慧, 吴小华. 控制性超促排卵过程中相关因子与卵母细胞质量关系的研究进展[J].中国优生与遗传杂志, 2019, 27(8): 1015-1019. LIU Xiaohui, WU Xiaohua. Relationships between serum and follicular fluid related factors and oocyte quality in controlled ovarian hyperstimulation[J]. Chinese Journal of Birth Health & Heredity, 2019, 27(8): 1015-1019. |
[6] | Botkjaer JA, Pors SE, Petersen TS, et al. Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development[J]. J Assist Reprod Genet, 2019, 36(5): 889-903. |
[7] | Stubbs SA, Webber LJ, StARk J, et al. Role of Insulin like growth factors in initiation of follicle growth in normal and polycystic human ovaries[J]. J Clin Endocr Metab, 2013, 98(8): 3298-3305. |
[8] | Oktem O, Yakin K, Oguz SY, et al. High responders are not exempt from detrimental effects of prematurely rising progesterone levels in fresh embryo transfer cycles[J]. Reprod Biomed Online, 2019, 8(2): 206-215. |
[9] | 胡琳莉, 黄国宁, 孙海翔. 多囊卵巢综合征中国诊疗指南[J]. 中华妇产科杂志, 2018, 53(1): 2-6. |
[10] | 马帅, 张蓓, 李媛. 多囊卵巢综合征诊断标准的变迁[J]. 中国计划生育和妇产科, 2020, 12(2): 6-9. |
[11] | 胡琳莉, 黄国宁, 孙海翔, 等. 辅助生殖技术临床关键指标质控专家共识[J]. 生殖医学杂志, 2018, 29(9): 828-835. HU Linli, HUANG Guoning, SUN Haixiang, et al. CSRM consensus on key indicators for quality control in ART clinical operation[J]. Journal of reproductive medicine, 2018, 29(9): 828-835. |
[12] | Shapiro MR, Wasserfall CH, McGrail SM, et al. Insulin-like growth factor dysregulation both preceding and following type 1 diabetes diagnosis[J]. Diabetes, 2020, 69(3): 413-423. |
[13] | Junguo C, Qingchun M, Haiyan H. The roles of insulin-like growth factor 2 mRNA-binding protein 2 in cancer and cancer stem cells[J]. Stem Cells International, 2018, 2018: 4217259. doi: 10.1155/2018/4217259.eCollection 2018. |
[14] | Zaanan A, Calmel C, Henriques J, et al. High IGF1R protein expression correlates with disease-free survival of patients with stage III colon cancer[J]. Cell Oncology, 2020, 43(2): 237-247. |
[15] | Tahara T, Tahara S, Horiguchi N, et al. Methylation status of IGF DMR and LINE1 in leukocyte DNA provides distinct clinicopatho-logical features of gastric cancer patients[J]. Clinical & Experimental Medicine, 2018, 18(2): 215-220. |
[16] | Hobeika E, Armouti M, Fierro MA, et al. Regulation of insulin-like growth factor 2 by oocyte-secreted factors in primary human granulosa cells[J]. J Clin Endocrinol Metab, 2020, 105(1): 327-335. |
[17] | Ramos Cirilo PD, Rosa FE, Moreira Ferraz MF, et al. Genetic polymorphisms associated with steroids metabolism and insulin action in polycystic ovary syndrome[J]. Gynecol Endocrinol, 2012, 28(3): 190-194. |
[18] | Sarah C Baumgarten, Scott M Convissar, A Musa Zamah, et al. FSH regulates IGF2 expression in human granulosa cells in an AKT-dependent manner[J]. Orginal article, 2015, 100(8): E1046-1055. |
[19] | Zhong G, Chen B. Serum and follicular fluid levels of IGF-II,IGF-binding protein-4 and pregnancy associated plasma protein A in controlled ovarian hyperstimulation cycle between polycystic ovarian syndrome(PCOS)and non-PCOS women[J]. Gynecol Endocrinol, 2011, 27(2): 86-90. |
[20] | Hwang Kwon,Dong Hee Choi, Jee Hyeon Vae, et al.mRNA expression pattern of insulin like growth factor components of granulose cells and cumulus cells in women with and without polycystic ovary syndrome according to oocyte maturity[J]. Fertil Steril, 2010, 94(6): 2417-2420. |
[21] | 潘荣, 于岭, 王涛, 等. 获卵数与IVF/ICSI的相关性研究[J]. 生殖医学杂志, 2018, 27(2): 117-122. PAN Rong, YU Ling, WANG Tao, et al. Association of number of oocytes retrieved with cumulative live birth rate of IVF/ICSI[J]. Journal of Reproductive Medicine, 2018, 27(2): 117-122. |
[22] | Ji J, Liu Y, Tong XH, et al. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China[J]. Hum Reprod, 2013, 28(10): 2728-2734. |
[23] | 刘文杰, 贾朝霞, 郭杉, 等. PCOS与非PCOS患者卵巢过度刺激综合征的预测因子分析[J]. 生殖医学杂志, 2019, 6(28): 593-600. LIN Wenjie, JIA Zhaoxia, GUO Shan, et al. Predictors of ovarian hyperstimulation syndrome in patients with/without polycystic ovarian syndrome[J]. Journal of Reproductive Medicine, 2019, 6(28): 593-600. |
[24] | 范树明, 马文敏, 徐娇燕, 等. PCOS 患者在试管治疗中胚胎的发育潜能性分析[J]. 中国优生与遗传学杂志, 2019, 27(10): 1251-1253. FAN Shuming, MA Wenmin, XU Jiaoyan, et al. Analysis of developmental potential of embryos in PCOS patients in vitro[J]. Chinese Journal of Birth Health & Heredity, 2019, 27(10): 1251-1253. |
[25] | 路红琴, 何玉洁. 长方案周期中女性年龄和获卵数对妊娠结局的影响[J]. 生殖医学杂志, 2019, 28(9): 1017-1026. LU Hongqin, HE Yujie. Impact of female age and number of oocytes retrieved on clinical outcome of IVF/ICSI with long protocol of controlled ovarian hyperstimulation[J]. Journal of Reproductive Medicine, 2019, 28(9): 1017-1026. |
[26] | 陈莉, 张艳, 张珠兰. 血清中胰岛素样生长因子系统与早期自然流产相关性研究[J]. 国际检验医学杂志, 2011, 32(2): 169-170. CHEN Li, ZHANG Yan, ZHANG Zhulan. The relationship between serum insulin like growth factor system and early spontaneous abortion[J]. International Journal of Laboratory Medicine, 2011, 32(2): 169-170. |
[27] | 周萍, 邹丽. 早孕绒毛滋养层细胞胰岛素生长因子-II mRNA表达与胚胎发育的关系[J]. 现代妇产科进展, 2004, 13(3): 207-209. ZHOU Ping, ZOU Li. The relationship between the expression of IGF-II mRNA in human villus and the embryo development[J]. Advances in Modern Obstetrics and Gynecology, 2004, 13(3): 207-209. |
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