León-Félix Cecibel M, Ouni Emna, Herinckx Gaëtan, Vertommen Didier, Amorim Christiani A, Lucci Carolina M
Institute of Biological Sciences, Department of Physiology, University of Brasilia, Brasilia 70910-900, Brazil.
Tumor Cell Dynamics Unit, Inserm U1279, Gustave Roussy Institute, Université Paris-Saclay, Villejuif 94800, France.
J Proteomics. 2025 Jan 16;311:105347. doi: 10.1016/j.jprot.2024.105347. Epub 2024 Nov 7.
Recent approaches of regenerative reproductive medicine investigate the decellularized extracellular matrix to develop a transplantable engineered ovary (TEO). However, a full proteomic analysis is not usually performed after the decellularization process to evaluate the preservation of the extracellular matrix (ECM). In this study, the ECM of the bovine ovarian cortex was analyzed before and after decellularization using mass spectrometry and bioinformatics. A total of 155 matrisome proteins were identified in the native ECM of the bovine ovarian cortex, with 145 matrisome proteins detected in the decellularized ECM. After decellularization, only 10 matrisome proteins were lost, and notably, none belonged to the category of reproductive biological processes. Histology and histochemistry analyses were employed to assess the general morphology of both native and decellularized ECM, allowing for the identification of the most abundant ECM proteins. Moreover, our study highlighted collagen type VI alpha 3 and heparan sulfate proteoglycan 2 as the most abundant components in the bovine ovarian ECM, mirroring the composition observed in the human ovary. These findings enhance our understanding of the composition of both native and decellularized ECM, with the potential implications for the development of a TEO. SIGNIFICANCE: The significance of the present study lies on the possibility of advancing towards developing a bioengineered ovary, which is the ultimate strategy to regain fertility in women. The results demonstrate that the decellularized extracellular matrix of the bovine ovary maintains the protein composition of the native matrisome, using a recently described decellularization protocol. The decellularized matrix may serve as scaffolding for seeding ovarian stromal cells and follicles to create a bioengineered ovary, and as closer its composition is to the native matrix the better. Also, comparing the bovine ovarian matrisome, which was described for the first time here, with the human ovarian matrisome, we could see a great similarity, suggesting that the bovine ovary decellularized matrix may serve as a model for developing a human bioengineered ovary.
再生生殖医学的最新研究方法是研究脱细胞的细胞外基质，以开发可移植的工程化卵巢（TEO）。然而，脱细胞过程后通常不会进行完整的蛋白质组分析来评估细胞外基质（ECM）的保存情况。在本研究中，使用质谱和生物信息学分析了牛卵巢皮质脱细胞前后的ECM。在牛卵巢皮质的天然ECM中总共鉴定出155种基质体蛋白，在脱细胞的ECM中检测到145种基质体蛋白。脱细胞后，仅10种基质体蛋白丢失，值得注意的是，没有一种属于生殖生物学过程类别。采用组织学和组织化学分析来评估天然和脱细胞ECM的一般形态，从而鉴定出最丰富的ECM蛋白。此外，我们的研究强调VI型胶原蛋白α3和硫酸乙酰肝素蛋白聚糖2是牛卵巢ECM中最丰富的成分，这与在人卵巢中观察到的组成情况相似。这些发现加深了我们对天然和脱细胞ECM组成的理解，对TEO的开发具有潜在意义。意义：本研究的意义在于有可能朝着开发生物工程卵巢迈进，这是恢复女性生育能力的最终策略。结果表明，使用最近描述的脱细胞方案，牛卵巢的脱细胞细胞外基质保持了天然基质体的蛋白质组成。脱细胞基质可作为接种卵巢基质细胞和卵泡以创建生物工程卵巢的支架，其组成与天然基质越接近越好。此外，将此处首次描述的牛卵巢基质体与人类卵巢基质体进行比较，我们可以看到很大的相似性，这表明牛卵巢脱细胞基质可作为开发人类生物工程卵巢的模型。
