BACKGROUND Successful ovulation is essential for natural conception and fertility. Defects in the ovulatory process are associated with various conditions of infertility or subfertility in women. However, our understanding of the intra-ovarian biochemical mechanisms underlying this process in women has lagged compared to our understanding of animal models. This has been largely due to the limited availability of human ovarian samples that can be used to examine changes across the ovulatory period and delineate the underlying cellular/molecular mechanisms in women. Despite this challenge, steady progress has been made to improve our knowledge of the ovulatory process in women by: (i) collecting granulosa cells across the IVF interval, (ii) creating a novel approach to collecting follicular cells and tissues across the periovulatory period from normally cycling women, and (iii) developing unique in vitro models to examine the LH surge or hCG administration-induced ovulatory changes in gene expression, the regulatory mechanisms underlying the ovulatory changes, and the specific functions of the ovulatory factors. OBJECTIVE AND RATIONALE The objective of this review is to summarize findings generated using in vivo and in vitro models of human ovulation, with the goal of providing new insights into the mechanisms underlying the ovulatory process in women. SEARCH METHODS This review is based on the authors’ own studies and a search of the relevant literature on human ovulation to date using PubMed search terms such as ‘human ovulation EGF-signaling’, ‘human ovulation steroidogenesis’, ‘human ovulation transcription factor’, ‘human ovulation prostaglandin’, ‘human ovulation proteinase’, ‘human ovulation angiogenesis’ ‘human ovulation chemokine’, ‘human ovulatory disorder’, ‘human granulosa cell culture’. Our approach includes comparing the data from the authors’ studies with the existing microarray or RNA-seq datasets generated using ovarian cells obtained throughout the ovulatory period from humans, monkeys, and mice. OUTCOMES Current findings from studies using in vivo and in vitro models demonstrate that the LH surge or hCG administration increases the expression of ovulatory mediators, including EGF-like factors, steroids, transcription factors, prostaglandins, proteolytic systems, and other autocrine and paracrine factors, similar to those observed in other animal models such as rodents, ruminants, and monkeys. However, the specific ovulatory factors induced, their expression pattern, and their regulatory mechanisms vary among different species. These species-specific differences stress the necessity of utilizing human samples to delineate the mechanisms underlying the ovulatory process in women. WIDER IMPLICATIONS The data from human ovulation in vivo and in vitro models have begun to fill the gaps in our understanding of the ovulatory process in women. Further efforts are needed to discover novel ovulatory factors. One approach to address these gaps is to improve existing in vitro models to more closely mimic in vivo ovulatory conditions in humans. This is critically important as the knowledge obtained from these human studies can be translated directly to aid in the diagnosis of ovulation-associated pathological conditions, for the development of more effective treatment to help women with anovulatory infertility or, conversely, to better manage ovulation for contraceptive purposes. REGISTRATION NUMBER N/A.

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对人类卵巢排卵过程的新见解


背景技术成功排卵对于自然受孕和生育能力至关重要。排卵过程的缺陷与女性不孕或生育力低下的各种状况有关。然而，与我们对动物模型的理解相比，我们对女性这一过程背后的卵巢内生化机制的理解滞后。这主要是由于可用于检查排卵期变化并描绘女性潜在细胞/分子机制的人类卵巢样本的可用性有限。尽管面临这一挑战，我们在提高我们对女性排卵过程的了解方面取得了稳步进展，方法是：（i）在 IVF 间隔期间收集颗粒细胞，（ii）创建一种在排卵期间收集卵泡细胞和组织的新方法正常周期的女性，以及（iii）开发独特的体外模型来检查 LH 激增或 hCG 给药引起的排卵基因表达变化、排卵变化背后的调节机制以及排卵因子的具体功能。目的和基本原理本次综述的目的是总结使用人类排卵体内和体外模型得出的研究结果，目的是为女性排卵过程的潜在机制提供新的见解。 搜索方法 本综述基于作者自己的研究以及使用 PubMed 搜索术语（例如“人类排卵 EGF 信号传导”、“人类排卵类固醇生成”、“人类排卵转录因子”）对迄今为止人类排卵相关文献的检索。 、“人排卵前列腺素”、“人排卵蛋白酶”、“人排卵血管生成”、“人排卵趋化因子”、“人排卵障碍”、“人颗粒细胞培养物”。我们的方法包括将作者研究的数据与现有的微阵列或 RNA-seq 数据集进行比较，这些数据集是使用从人类、猴子和小鼠的整个排卵期获得的卵巢细胞生成的。结果目前使用体内和体外模型的研究结果表明，LH 激增或 hCG 给药会增加排卵介质的表达，包括 EGF 样因子、类固醇、转录因子、前列腺素、蛋白水解系统以及其他自分泌和旁分泌因子，与在其他动物模型（例如啮齿动物、反刍动物和猴子）中观察到的结果类似。然而，不同物种诱导的具体排卵因子、其表达模式及其调节机制各不相同。这些物种特异性差异强调了利用人类样本来描述女性排卵过程背后机制的必要性。更广泛的影响来自人类排卵体内和体外模型的数据已经开始填补我们对女性排卵过程理解的空白。需要进一步努力发现新的排卵因子。解决这些差距的一种方法是改进现有的体外模型，以更接近地模拟人类体内的排卵条件。 这一点至关重要，因为从这些人类研究中获得的知识可以直接转化为帮助诊断与排卵相关的病理状况，开发更有效的治疗方法来帮助患有无排卵性不孕症的女性，或者相反，更好地管理排卵避孕目的。注册号 不适用。