卵巢低反应患者的卵泡液和颗粒细胞中 GDF9 和 BMP15 基因表达随年龄增长而下降。
Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders.
机构信息
Reproductive Medicine Center, Sichuan Provincial Women's and Children's Hospital, The Affiliated Women's and Children's Hospital of Chengdu Medical College, 290 Shayan West Second Street, Wuhou District, Chengdu, 610045, Sichuan, China.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37 Guoxuexiang, Wuhou District, Chengdu, 610041, Sichuan, China.
出版信息
J Ovarian Res. 2021 Jan 4;14(1):1. doi: 10.1186/s13048-020-00757-x.
BACKGROUND
Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment.
METHODS
A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A (< 35 year old), group B (35-40 year old), and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.
RESULTS
Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P < 0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P < 0.05), showing a trend of decline along with age. The ratio of GDF9/BMP15 mRNA levels were similar among the three groups (P > 0.05). The relative levels of GDF9 and BMP15 proteins in GCs have correlated with the relative mRNA levels in GCs and protein concentrations in FF (P < 0.05).
CONCLUSIONS
For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined along with increased age and in accompany with poorer oocyte quality and IVF outcome, whilst the ratio of GDF9/BMP15 mRNA levels remained relatively constant.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Center ( ChiCTR1800016107 ). Registered on 11 May 2018.
背景
生长分化因子 9（GDF9）和骨形态发生蛋白 15（BMP15）基因在卵泡发生中起重要作用。在卵巢反应不良（POR）患者中发现这两种基因的表达发生了改变。在这项前瞻性队列研究中，我们确定了按年龄分组的 POR 患者的卵泡液（FF）和颗粒细胞（GC）中 GDF9 和 BMP15 基因的表达，并探讨了其与体外受精和胚胎移植（IVF-ET）治疗结果的关系。
方法
本研究共纳入 196 例来自三级教学医院的 POR 患者。根据博洛尼亚标准诊断患者，并分为 A 组（<35 岁）、B 组（35-40 岁）和 C 组（>40 岁）。所有患者均采用 GnRH 拮抗剂方案，在取卵后收集 FF 和 GCs。采用酶联免疫吸附试验（ELISA）、实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测 FF 和 GCs 中 GDF9 和 BMP15 基因的表达。
结果
与 C 组相比，A 组和 B 组的 2 原核（2PN）卵母细胞和可移植胚胎明显增多，着床率和临床妊娠率也明显升高（P<0.05）。FF 和 GCs 中 GDF9 和 BMP15 基因的表达水平在三组间差异有统计学意义（P<0.05），且随年龄呈下降趋势。三组 GDF9/BMP15 mRNA 比值相似（P>0.05）。GC 中 GDF9 和 BMP15 蛋白的相对水平与 GC 中的相对 mRNA 水平和 FF 中的蛋白浓度相关（P<0.05）。
结论
对于卵巢反应不良的患者，特别是年龄超过 40 岁的患者，GDF9 和 BMP15 的表达随年龄增长而下降，同时伴有卵母细胞质量和 IVF 结局较差，而 GDF9/BMP15 mRNA 比值保持相对稳定。
试验注册
中国临床试验注册中心（ChiCTR1800016107）。注册于 2018 年 5 月 11 日。
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