Department of Animal Science, University of California Davis, 450 Bioletti Way, Davis, CA 95616, United States.
Department of Animal Science, University of California Davis, 450 Bioletti Way, Davis, CA 95616, United States.
Animal. 2023 May;17 Suppl 1:100743. doi: 10.1016/j.animal.2023.100743.
The pituitary gonadotropin FSH is a glycoprotein critical for the development of ovarian follicles. Upon binding to its G protein-coupled membrane receptor located on the granulosa cells of ovarian follicles, FSH elicits a cascade of downstream intracellular responses to promote follicle growth, maturation and steroidogenic activity, leading to the acquisition of meiotic and developmental competence of the enclosed oocyte. The essential role of FSH for proper antral follicle development and fertility is indisputable; over the decades, increasing evidence has also pointed toward survival and growth-promoting effects elicited by FSH in earlier-stage preantral follicles, deeming these follicles FSH-responsive as opposed to the FSH-dependent antral follicles. Transgenic mouse models lacking GnRH1, Fshβ or Fshr clearly demonstrate this difference by showing that, morphologically, preantral follicles develop to the secondary stage without FSH signaling; however, exogenous expression or administration of FSH to hormone-deficient mice promotes preantral follicle development, with more pronounced effects seen in earlier stages (i.e., primary follicles). In hypophysectomized sheep, FSH administration also promotes the growth of primary-stage preantral follicles. However, in vivo studies in this area are more challenging to perform in domestic animals compared to rodents, and therefore most of the research to date has been done in vitro. Here, we present the existing evidence for a role of FSH in regulating the growth and survival of preantral follicles from data generated in rodents and domestic animals. We provide an overview of the process of folliculogenesis, FSH synthesis and cellular signaling, and the response to FSH by preantral follicles in vivo and in vitro, as well as interactions between FSH and other molecules to regulate preantral folliculogenesis. The widespread use of FSH in ovarian stimulation programs for assisted reproduction creates a real need for a better understanding of the effects of FSH beyond stimulation of antral follicle growth, and more research in this area could lead to the development of more effective fertility programs. In addition to its importance as an agricultural species, the cow provides a desirable model for humans regarding ovarian stimulation due to similar timing of folliculogenesis and follicle size, as well as similar ovarian architecture. The refinement of minimally invasive methods to allow the study of preantral folliculogenesis in live animals will be critical to understand the short- and long-term effects of FSH in ovarian folliculogenesis.
垂体促性腺激素 FSH 是一种糖蛋白，对卵巢卵泡的发育至关重要。当它与位于卵巢卵泡颗粒细胞上的 G 蛋白偶联膜受体结合时，FSH 会引发一系列下游细胞内反应，以促进卵泡生长、成熟和类固醇生成活性，从而获得被包裹的卵母细胞的减数分裂和发育能力。FSH 对正常窦前卵泡发育和生育能力的重要作用是无可争议的；几十年来，越来越多的证据也指出 FSH 在窦前卵泡的早期阶段产生的生存和生长促进作用，将这些卵泡视为 FSH 反应性的，而不是 FSH 依赖性的窦前卵泡。缺乏 GnRH1、Fshβ 或 Fshr 的转基因小鼠模型清楚地表明了这一差异，表明在形态上，没有 FSH 信号时，窦前卵泡发育到二级阶段；然而，外源性表达或给予激素缺乏的小鼠 FSH 会促进窦前卵泡的发育，在早期阶段（即初级卵泡）效果更为明显。在去垂体绵羊中，FSH 的给药也促进了初级窦前卵泡的生长。然而，与啮齿动物相比，在家畜中进行这一领域的体内研究更具挑战性，因此迄今为止，大部分研究都是在体外进行的。在这里，我们从啮齿动物和家畜的数据中提出了 FSH 在调节窦前卵泡生长和存活中的作用的现有证据。我们提供了一个概述，说明卵泡发生过程、FSH 的合成和细胞信号转导，以及 FSH 在体内和体外对窦前卵泡的反应，以及 FSH 与其他分子之间的相互作用，以调节窦前卵泡发生。FSH 在辅助生殖的卵巢刺激方案中的广泛应用确实需要更好地了解 FSH 除了刺激窦前卵泡生长之外的作用，而在这一领域的更多研究可能会导致更有效的生育方案的发展。除了作为一个农业物种的重要性外，由于奶牛的卵泡发生时间和卵泡大小相似，以及卵巢结构相似，因此它也是人类卵巢刺激的理想模型。完善微创方法，以便在活体动物中研究窦前卵泡发生，对于了解 FSH 在卵巢卵泡发生中的短期和长期作用至关重要。
