School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, People's Republic of China.
Reprod Biol Endocrinol. 2018 Mar 27;16(1):28. doi: 10.1186/s12958-018-0349-7.
Excessive nerve growth factor (NGF) is commonly found in the follicular fluid of patients with polycystic ovary syndrome (PCOS). Furthermore, oocytes from PCOS patients exhibit lower developmental competence. The purpose of this study was to explore the association between excessive NGF and low oocyte competence in vitro.
Excessive NGF was added to mouse cumulus oocyte complexes (COCs) cultured in vitro to investigate meiotic maturation of the oocyte. After culture, mRNA expression levels of Pfkp and Ldha genes in cumulus cells (CCs) and Gdf9, Bmp15 and Fgf8 genes in oocytes, were determined by real-time quantitative polymerase chain reaction (qPCR). We also investigated the mRNA content of Pfkp and Ldha in CCs from PCOS and non-PCOS patients.
Excessive NGF significantly inhibited oocyte meiotic maturation. The inhibitory effect was mediated by the NGF high-affinity receptor, NTRK1. mRNA content of Pfkp and Ldha genes in CCs was significantly reduced by excessive NGF stimulation. Moreover, the expression levels of Gdf9, Bmp15 and Fgf8 were also decreased in oocytes, and was induced by excessive NGF-stimulated CCs. In addition, lower expression levels of Pfkp and Ldha in CCs were identified in Chinese PCOS patients with excessive NGF (PCOS, 22 ± 2.63 ng/ml, n = 13; non-PCOS, 7.18 ± 2.42 ng/ml, n = 9; p < 0.01) in the follicular fluid, suggesting a potential association between excessive NGF and decreased glycolysis in the CCs of women with PCOS.
Excessive NGF impairs bidirectional communication between oocyte and cumulus cells, which might be related to low oocyte competence.
多囊卵巢综合征(PCOS)患者的卵泡液中通常存在过量的神经生长因子(NGF)。此外,PCOS 患者的卵母细胞发育能力较低。本研究旨在探讨过量 NGF 与体外卵母细胞发育能力低下之间的关系。
在体外培养的小鼠卵丘-卵母细胞复合物(COC)中添加过量的 NGF,以研究卵母细胞的减数分裂成熟情况。培养后,通过实时定量聚合酶链反应(qPCR)检测卵丘细胞(CC)中 Pfkp 和 Ldha 基因以及卵母细胞中 Gdf9、Bmp15 和 Fgf8 基因的 mRNA 表达水平。我们还研究了 PCOS 和非 PCOS 患者 CC 中 Pfkp 和 Ldha 的 mRNA 含量。
过量的 NGF 显著抑制卵母细胞的减数分裂成熟。这种抑制作用是通过 NGF 高亲和力受体 NTRK1 介导的。过量 NGF 刺激显著降低 CC 中 Pfkp 和 Ldha 基因的 mRNA 含量。此外,卵母细胞中 Gdf9、Bmp15 和 Fgf8 的表达水平也降低,这是由过量 NGF 刺激的 CC 诱导的。此外,在中国 PCOS 患者的卵泡液中,发现 Pfkp 和 Ldha 在 CC 中的表达水平较低,且 NGF 水平升高(PCOS,22 ± 2.63 ng/ml,n = 13;非 PCOS,7.18 ± 2.42 ng/ml,n = 9;p < 0.01),提示 PCOS 妇女 CC 中过量 NGF 与糖酵解降低之间可能存在关联。
过量的 NGF 损害了卵母细胞与卵丘细胞之间的双向通讯,这可能与卵母细胞发育能力低下有关。