Research and Educational Resource Centre for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples' Friendship University of Russia, 117198 Moscow, Russia.
Research Institute of Experimental Biology and Medicine, Burdenko Voronezh State Medical University, 394036 Voronezh, Russia.
Int J Mol Sci. 2023 Mar 30;24(7):6498. doi: 10.3390/ijms24076498.
The mechanisms of ovarian endometrioid cyst formation, or cystic ovarian endometriosis, still remain to be elucidated. To address this issue, we analyzed the involvement of mast cell (MC) tryptase and carboxypeptidase A3 (CPA3) in the development of endometriomas. It was found that the formation of endometrioid cysts was accompanied by an increased MC population in the ovarian medulla, as well as by an MC appearance in the cortical substance. The formation of MC subpopulations was associated with endometrioma wall structures. An active, targeted secretion of tryptase and CPA3 to the epithelium of endometrioid cysts, immunocompetent cells, and the cells of the cytogenic ovarian stroma was detected. The identification of specific proteases in the cell nuclei of the ovarian local tissue microenvironment suggests new mechanisms for the regulatory effects of MCs. The cytoplasmic outgrowths of MCs propagate in the structures of the stroma over a considerable distance; they offer new potentials for MC effects on the structures of the ovarian-specific tissue microenvironment under pathological conditions. Our findings indicate the potential roles of MC tryptase and CPA3 in the development of ovarian endometriomas and infer new perspectives on their uses as pharmacological targets in personalized medicine.
卵巢子宫内膜样囊肿形成的机制，或囊性卵巢子宫内膜异位症，仍有待阐明。为了解决这个问题，我们分析了肥大细胞（MC）类胰蛋白酶和羧肽酶 A3（CPA3）在子宫内膜异位瘤发展中的作用。结果发现，子宫内膜样囊肿的形成伴随着卵巢髓质中 MC 群体的增加，以及皮质物质中 MC 的出现。MC 亚群的形成与子宫内膜异位瘤壁结构有关。检测到类胰蛋白酶和 CPA3 主动、靶向分泌到子宫内膜样囊肿上皮、免疫活性细胞和细胞遗传卵巢基质细胞。在卵巢局部组织微环境的细胞核中鉴定出特定的蛋白酶，提示了 MC 调节作用的新机制。MC 的细胞质突起在基质结构中远距离传播；它们为 MC 在病理条件下对卵巢特异性组织微环境结构的影响提供了新的潜力。我们的研究结果表明 MC 类胰蛋白酶和 CPA3 在卵巢子宫内膜异位瘤的发展中可能发挥作用，并推断出它们作为个性化药物治疗中药理学靶点的新前景。
