Centre de Recherche en Reproduction Animale, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Quebec, Canada.
Biol Reprod. 2010 Sep;83(3):339-46. doi: 10.1095/biolreprod.110.084277. Epub 2010 May 19.
Fibroblast growth factors (FGF) are involved in paracrine signaling between cell types in the ovarian follicle. FGF8, for example, is secreted by oocytes and controls cumulus cell metabolism. The closely related FGF18 is also expressed in oocytes in mice. The objective of this study was to assess the potential role of FGF18 in follicle growth in a monovulatory species, the cow. Messenger RNA encoding FGF18 was detected primarily in theca cells, and in contrast to the mouse, FGF18 was not detected in bovine oocytes. Addition of FGF18 protein to granulosa cell cultures inhibited estradiol and progesterone secretion as well as the abundance of mRNA encoding steroidogenic enzymes and the follicle-stimulating hormone receptor. In vivo, onset of atresia of the subordinate follicle was associated with increased thecal FGF18 mRNA levels and FGF18 protein in follicular fluid. In vitro, FGF18 altered cell cycle progression as measured by flow cytometry, resulting in increased numbers of dead cells (sub-G1 peak) and decreased cells in S phase. This was accompanied by decreased levels of mRNA encoding the cell cycle checkpoint regulator GADD45B. Collectively, these data point to a unique role for this FGF in signaling from theca cells to granulosa cells and suggest that FGF18 influences the process of atresia in ovarian follicles.
成纤维细胞生长因子 (FGF) 参与卵巢卵泡中细胞类型之间的旁分泌信号传递。例如，FGF8 由卵母细胞分泌，控制着卵丘细胞的代谢。在小鼠中，密切相关的 FGF18 也在卵母细胞中表达。本研究的目的是评估 FGF18 在单排卵物种牛的卵泡生长中的潜在作用。编码 FGF18 的信使 RNA 主要在卵泡膜细胞中检测到，与小鼠不同，牛卵母细胞中未检测到 FGF18。将 FGF18 蛋白添加到颗粒细胞培养物中，抑制了雌二醇和孕酮的分泌，以及编码甾体生成酶和卵泡刺激素受体的 mRNA 的丰度。在体内，从属卵泡发生闭锁与卵泡膜 FGF18 mRNA 水平和卵泡液中 FGF18 蛋白的增加有关。在体外，FGF18 改变了细胞周期进程，如通过流式细胞术测量的，导致死细胞（Sub-G1 峰）数量增加和 S 期细胞减少。这伴随着细胞周期检查点调节剂 GADD45B 的 mRNA 水平降低。总的来说，这些数据表明这种 FGF 在卵泡膜细胞向颗粒细胞的信号传递中具有独特的作用，并表明 FGF18 影响卵巢卵泡的闭锁过程。
