Human and Animal Physiology, Wageningen University and Research, AH, Wageningen, The Netherlands.
Adaptation Physiology, Wageningen University and Research, AH, Wageningen, The Netherlands.
Mol Hum Reprod. 2019 Oct 28;25(10):614-624. doi: 10.1093/molehr/gaz042.
Antral follicle size might be a valuable additive predictive marker for IVF outcome. To better understand consequences of antral follicle size as a marker for reproductive outcome, we aimed to obtain insight in follicle size-related granulosa cell processes, as granulosa cells play an essential role in follicular development via the production of growth factors, steroids and metabolic intermediates. Using the pig as a model, we compared gene expression in granulosa cells of smaller and larger follicles in the healthy antral follicle pool of sows, which had a high variation versus low variation in follicle size. Selected gene expression was confirmed at the protein level. Granulosa cells of smaller antral follicles showed increased cell proliferation, which was accompanied by a metabolic shift towards aerobic glycolysis (i.e. the Warburg effect), similar to other highly proliferating cells. High granulosa cell proliferation rates in smaller follicles might be regulated via increased granulosa cell expression of the androgen receptor and the epidermal growth factor receptor, which are activated in response to locally produced mitogens. While granulosa cells of smaller follicles in the pool are more proliferative, granulosa cells of larger follicles express more maturation markers such as insulin-like growth factor-1 (IGF1) and angiopoietin 1 (ANGPT1) and are therefore more differentiated. As both higher IGF1 and ANGPT1 have been associated with better IVF outcomes, the results of our study imply that including smaller follicles for oocyte aspiration might have negative consequences for IVF outcome.
窦卵泡大小可能是预测 IVF 结局的一个有价值的附加指标。为了更好地了解窦卵泡大小作为生殖结局标志物的后果，我们旨在深入了解卵泡大小相关的颗粒细胞过程，因为颗粒细胞通过产生生长因子、类固醇和代谢中间产物在卵泡发育中发挥着重要作用。我们使用猪作为模型，比较了在母猪健康窦卵泡池中卵泡大小高变异性与低变异性的小卵泡和大卵泡中的颗粒细胞基因表达。在蛋白质水平上验证了选定的基因表达。小窦卵泡的颗粒细胞显示出增加的细胞增殖，这伴随着向有氧糖酵解（即沃伯格效应）的代谢转变，类似于其他高度增殖的细胞。小卵泡中高颗粒细胞增殖率可能通过增加雄激素受体和表皮生长因子受体在颗粒细胞中的表达来调节，这些受体在受到局部产生的有丝分裂原的刺激时被激活。虽然池中小卵泡的颗粒细胞增殖更多，但大卵泡的颗粒细胞表达更多的成熟标志物，如胰岛素样生长因子 1（IGF1）和血管生成素 1（ANGPT1），因此分化程度更高。由于较高的 IGF1 和 ANGPT1 都与更好的 IVF 结局相关，我们的研究结果表明，将小卵泡纳入卵母细胞抽吸可能会对 IVF 结局产生负面影响。
