Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders.
Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders.
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DOI：
10.1186/s13048-020-00757-x
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发表时间：
2021-01-04
影响因子：
4
通讯作者：
Tan H
中科院分区：
文献类型：
--
作者：
Gong Y;Li-Ling J;Xiong D;Wei J;Zhong T;Tan H
生长分化因子 9 (GDF9) 和骨形态发生蛋白 15 (BMP15) 基因在卵泡发生中发挥重要作用。在卵巢反应不良（POR）的患者中发现了这两种蛋白的表达发生了改变。在这项前瞻性队列研究中，我们确定了按年龄分组的卵巢反应不良者的卵泡液 (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) 治疗结果的相关性。共有 196 名 POR 患者从三级教学医院入组。患者按照博洛尼亚标准诊断，分为A组（<35岁）、B组（35~40岁）、C组（>40岁）。对所有患者进行 GnRH 拮抗剂方案，并在卵母细胞取出后收集 FF 和 GC。通过酶联免疫吸附测定 (ELISA)、定量实时聚合酶链反应 (qRT-PCR) 和蛋白质印迹法测定 FF 和 GC 中 GDF9 和 BMP15 基因的表达。与C组相比，A组和B组的二原核（2PN）卵母细胞和可移植胚胎显着增多，着床率和临床妊娠率也更高（P<0.05）。 FF和GC中GDF9和BMP15基因的表达水平在三组之间差异显着（P＜0.05），并呈现随年龄增长而下降的趋势。三组间GDF9/BMP15 mRNA水平比值相似（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）。对于卵巢反应较差的人，特别是40岁以上的人，GDF9和BMP15的表达随着年龄的增长而下降，并伴随着卵母细胞质量和IVF结果的较差，而GDF9/BMP15 mRNA水平的比率保持相对恒定。中国临床试验注册中心（ChiCTR1800016107）。注册日期：2018 年 5 月 11 日。
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. 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. 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). 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. Chinese Clinical Trial Registry Center (ChiCTR1800016107). Registered on 11 May 2018.
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