Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Mounier 52, bte B1.52.02, Brussels 1200, Belgium.
Global Technical Enablement, SAS Institute GmbH, Heidelberg 69118, Germany.
Matrix Biol. 2022 May;109:91-120. doi: 10.1016/j.matbio.2022.03.005. Epub 2022 Mar 25.
Our modern era is witnessing an increasing infertility rate worldwide. Although some of the causes can be attributed to our modern lifestyle (e.g., persistent organic pollutants, late pregnancy), our knowledge of the human ovarian tissue has remained limited and insufficient to reverse the infertility statistics. Indeed, all efforts have been focused on the endocrine and cellular function in support of the cell theory that dates back to the 18th century, while the human ovarian matrisome is still under-described. Hereby, we unveil the extracellular side of the story during different periods of the ovary life, demonstrating that follicle survival and development, and ultimately fertility, would not be possible without its involvement. We examined the human ovarian matrisome and described its remodeling from prepuberty until menopause, creating the first ovarian proteomic codex. Here, we confidently identified and quantified 98 matrisome proteins present in the three ovary groups. Among them, 26 were expressed differently among age groups, delineating a peculiar matrisomal fingerprint at each stage. Such proteins could be potential biomarkers phenotyping ovarian ECM at each age phase of female reproductive life. Beyond proteomics, our study presents a unique approach to understanding the data and depicting the spatiotemporal ECM-intracellular signaling networks and remodeling with age through imaging, advanced text-mining based on natural language processing technology, machine learning, and data sonification. Our findings provide essential context for healthy ovarian physiology, identifying and characterizing disease states, and recapitulating physiological tissues or development in vitro. This comprehensive proteomics analysis represents the ovarian proteomic codex and contributes to an improved understanding of the critical roles that ECM plays throughout the ovarian life span.
我们所处的现代时代见证了全球范围内不孕率的不断上升。虽然一些原因可以归因于我们的现代生活方式（例如，持久性有机污染物、晚婚），但我们对人类卵巢组织的了解仍然有限，不足以扭转不孕统计数据。事实上，所有的努力都集中在内分泌和细胞功能上，以支持可以追溯到 18 世纪的细胞理论，而人类卵巢基质体仍然描述不足。在此，我们揭示了卵巢生命周期不同阶段的细胞外侧面，证明如果没有它的参与，卵泡的存活和发育以及最终的生育能力是不可能的。我们研究了人类卵巢基质体，并描述了它从青春期前到绝经期的重塑过程，创建了第一个卵巢蛋白质组学密码本。在这里，我们自信地鉴定并量化了存在于三组卵巢中的 98 种基质体蛋白。其中，26 种蛋白在不同年龄组之间的表达不同，在每个阶段描绘出独特的基质体指纹。这些蛋白可以作为潜在的生物标志物，对女性生殖生命每个阶段的卵巢细胞外基质进行表型分析。除了蛋白质组学，我们的研究还提供了一种独特的方法来理解数据，并通过成像、基于自然语言处理技术的高级文本挖掘、机器学习和数据音频化来描绘随年龄变化的细胞外基质-细胞内信号网络和重塑。我们的研究结果为健康的卵巢生理学提供了重要的背景信息，确定和描述了疾病状态，并在体外重现了生理组织或发育。这项全面的蛋白质组学分析代表了卵巢蛋白质组学密码本，有助于更好地理解细胞外基质在整个卵巢生命周期中所发挥的关键作用。
