BACKGROUND Folliculogenesis occurs in the highly dynamic environment of the ovary. Follicle cyclic recruitment, neo-angiogenesis, spatial displacement, follicle atresia and ovulation stand out as major events resulting from the interplay between mechanical forces and molecular signals. Morphological and functional changes to the growing follicle and to the surrounding tissue are required to produce oocytes capable of supporting preimplantation development to the blastocyst stage. OBJECTIVE AND RATIONALE This review will summarize the ovarian morphological and functional context that contributes to follicle recruitment, growth and ovulation, as well as to the acquisition of oocyte developmental competence. We will describe the changes occurring during folliculogenesis to the ovarian extracellular matrix (ECM) and to the vasculature, their influence on the mechanical properties of the ovarian tissue, and, in turn, their influence on the regulation of signal transduction. Also, we will outline how their dysregulation might be associated with pathologies such as polycystic ovary syndrome (PCOS), endometriosis or premature ovarian insufficiency (POI). Finally, for each of these three pathologies, we will highlight therapeutic strategies attempting to correct the altered biomechanical context in order to restore fertility. SEARCH METHODS For each area discussed, a systematic bibliographical search was performed, without temporal limits, using PubMed Central, Web of Science and Scopus search engines employing the keywords extracellular matrix, mechanobiology, biomechanics, vasculature, angiogenesis or signalling pathway in combination with: ovary, oogenesis, oocyte, folliculogenesis, ovarian follicle, theca, granulosa, cumulus, follicular fluid, corpus luteum, meiosis, oocyte developmental competence, preimplantation, polycystic ovary syndrome, premature ovarian insufficiency or endometriosis. OUTCOMES Through search engines queries, we yielded a total of 37 368 papers that were further selected based on our focus on mammals and, specifically, on rodents, bovine, equine, ovine, primates and human, and also were trimmed around each specific topic of the review. After the elimination of duplicates, this selection process resulted in 628 papers, of which 287 were cited in the manuscript. Among these, 89.2% were published in the past 22 years, while the remaining 8.0%, 2.4% or 0.3% were published during the 1990s, 1980s or before, respectively. During folliculogenesis, changes occur to the ovarian ECM composition and organization that, together with vasculature modelling around the growing follicle, are aimed to sustain its recruitment and growth, and the maturation of the enclosed oocyte. These events define the scenario in which mechanical forces are key to the regulation of cascades of molecular signals. Alterations to this context determine impaired folliculogenesis and decreased oocyte developmental potential, as observed in pathological conditions which are causes of infertility, such as PCOS, endometriosis or POI. WIDER IMPLICATIONS The knowledge of these mechanisms and the rules that govern them lay a sound basis to explain how follicles recruitment and growth are modulated, and stimulate insights to develop, in clinical practice, strategies to improve follicular recruitment and oocyte competence, particularly for pathologies like PCOS, endometriosis and POI.

中文翻译：

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卵泡生成过程中卵巢中的生物力学力和信号及其失调：对生育能力的影响

背景卵泡发生发生在卵巢高度动态的环境中。卵泡周期性募集、新血管生成、空间位移、卵泡闭锁和排卵作为机械力和分子信号之间相互作用的主要事件脱颖而出。需要对生长中的卵泡和周围组织进行形态学和功能上的改变，才能产生能够支持植入前发育至囊胚阶段的卵母细胞。目的和基本原理 本综述将总结有助于卵泡募集、生长和排卵以及卵母细胞发育能力获得的卵巢形态和功能背景。我们将描述卵泡发生过程中卵巢细胞外基质 (ECM) 和脉管系统发生的变化，它们对卵巢组织的机械特性的影响，进而影响信号转导的调节。此外，我们将概述它们的失调如何与多囊卵巢综合征 (PCOS)、子宫内膜异位症或卵巢功能不全 (POI) 等病症相关联。最后，对于这三种病症中的每一种，我们将强调试图纠正改变的生物力学环境以恢复生育能力的治疗策略。搜索方法 对于所讨论的每个领域，使用 PubMed Central、Web of Science 和 Scopus 搜索引擎，使用关键词细胞外基质、机械生物学、生物力学、脉管系统、血管生成或信号通路，并结合以下内容，进行了系统的书目搜索，没有时间限制： , 卵子发生, 卵母细胞, 卵泡发生、卵巢卵泡、卵泡膜、颗粒层、卵丘、卵泡液、黄体、减数分裂、卵母细胞发育能力、植入前、多囊卵巢综合征、卵巢功能不全或子宫内膜异位症。结果 通过搜索引擎查询，我们总共获得了 37 368 篇论文，这些论文是根据我们对哺乳动物的关注进一步选择的，特别是啮齿动物、牛、马、绵羊、灵长类动物和人类，并且还围绕每个特定主题进行了修剪评价。剔除重复后，这一选择过程产生了 628 篇论文，其中 287 篇在手稿中被引用。其中，89.2%是在过去22年发表的，其余8.0%、2.4%和0.3%分别是在1990年代、80年代或之前发表的。在卵泡发生过程中，卵巢 ECM 的组成和组织发生变化，连同生长卵泡周围的脉管系统建模，旨在维持其募集和生长，以及封闭卵母细胞的成熟。这些事件定义了机械力是调节分子信号级联的关键的场景。对这种情况的改变决定了卵泡发生受损和卵母细胞发育潜能降低，正如在导致不孕症的病理条件下所观察到的那样，例如 PCOS、子宫内膜异位症或 POI。更广泛的意义 这些机制的知识和管理它们的规则为解释卵泡募集和生长是如何被调节奠定了坚实的基础，并激发了在临床实践中开发改善卵泡募集和卵母细胞能力的策略的见解，