During folliculogenesis, the gonadotrophin (GTH)-dependent phase begins at the small antral follicle stage and ends with Graafian follicles. In this study, pregnant mare’s serum GTH was used to induce GTH-dependent folliculogenesis in mice, following which the developmental events that follicles undergo, as well as the underlying regulatory signals, were investigated at both the morphological and transcriptomic level. GTH-dependent folliculogenesis consisted of three phases: preparation, rapid growth and decelerated growth. In the preparation phase, comprising the first 12 h, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and reduced protein synthesis and processing. The rapid growth phase lasted from 12 to 24 h; in this phase, granulosa cells completed their proliferation, and follicles acquired the capacity for estradiol secretion and ovulation. Meanwhile, the decelerating growth phase occurred between 24 and 48 h of GTH-dependent folliculogenesis. In this phase, the proliferation and expansion of the follicular antrum were reduced, energy metabolism was shifted to oxidative phosphorylation, and cell migration and lipid metabolism were enhanced in preparation for luteinization. We also revealed the key signaling pathways that regulate GTH-dependent folliculogenesis and elucidated the activation sequence of these pathways. A comparison of our RNA-sequencing data with that reported for humans suggested that the mechanisms involved in mouse and human folliculogenesis are evolutionarily conserved. In this study, we draw a detailed atlas of GTH-dependent folliculogenesis, thereby laying the foundation for further investigation of the regulatory mechanisms underlying this process.

中文翻译：

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小鼠模型揭示了卵泡发育的促性腺激素依赖性阶段的事件和潜在的调节信号

在卵泡发生期间，促性腺激素 (GTH) 依赖性阶段开始于小窦卵泡阶段，并以 Graafian 卵泡结束。在这项研究中，怀孕母马的血清 GTH 用于诱导小鼠的 GTH 依赖性卵泡发生，随后在形态学和转录组水平上研究卵泡经历的发育事件以及潜在的调节信号。GTH 依赖性卵泡发生包括三个阶段：准备阶段、快速生长阶段和减速生长阶段。在准备阶段，包括前 12 小时，颗粒细胞完成了增殖和分化的准备工作，将能量代谢转变为糖酵解，并减少了蛋白质的合成和加工。快速生长期持续12～24 h；在这个阶段，颗粒细胞完成了它们的增殖，和卵泡获得雌二醇分泌和排卵的能力。同时，减速生长期发生在 GTH 依赖性卵泡发生的 24 至 48 小时之间。在这个阶段，卵泡窦的增殖和扩张减少，能量代谢转向氧化磷酸化，细胞迁移和脂质代谢增强，为黄体化做准备。我们还揭示了调节 GTH 依赖性卵泡发生的关键信号通路，并阐明了这些通路的激活序列。将我们的 RNA 测序数据与人类报告的数据进行比较表明，涉及小鼠和人类卵泡发生的机制在进化上是保守的。在这项研究中，我们绘制了 GTH 依赖性卵泡发生的详细图谱，