Ma Suke, Hirata Tetsuya, Arakawa Tomoko, Sun Hui, Neriishi Kazuaki, Fukuda Shinya, Nakazawa Akari, Wang Yu, Harada Miyuki, Hirota Yasushi, Koga Kaori, Wada-Hiraike Osamu, Fujii Tomoyuki, Osuga Yutaka
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Reprod Sci. 2020 Jan;27(1):443-452. doi: 10.1007/s43032-019-00041-4. Epub 2020 Jan 1.
Human endometrium is a highly regenerative and dynamic tissue that undergoes cyclic changes during menstrual cycle. It has been reported that endometrial epithelium contains a population of progenitor/stem cells. Increasing amount of evidence indicates that progenitor/stem cells are involved in the pathogenesis of endometriosis. Proteins belonging to the aldehyde dehydrogenase 1 (ALDH1A) family have been reported to be markers of normal tissue stem cells and cancer stem cells. In this study, by using immunohistochemistry, we examined the expression of ALDH1A isozymes in human endometrial tissue, including that affected by endometriosis, and in ovarian endometrioma. Positive staining for ALDH1A isozymes was observed in the stroma of the endometrium and in endometriotic ovarian tissue. In the glands, expression patterns were distinct for different ALDH1A isozymes. ALDH1A1 and ALDH1A3 were highly expressed in the epithelium of stratum basalis of the endometrium and in the epithelium of ovarian endometrioma irrespective of the menstrual cycle, whereas ALDH1A2 was highly expressed only in the epithelium of endometrioma. Furthermore, ALDH1A1 co-localized with N-cadherin, which is a marker of endometrial epithelial progenitor cells, in the glands of stratum basalis. These findings support and reinforce the notion about the presence of progenitor/stem cells in endometrial glands in stratum basalis and in endometriotic glands, suggesting that these cells are involved in the physiology of the endometrium and in the pathology of endometriosis.
人类子宫内膜是一种高度再生且动态变化的组织，在月经周期中会经历周期性变化。据报道，子宫内膜上皮中含有一群祖细胞/干细胞。越来越多的证据表明，祖细胞/干细胞参与了子宫内膜异位症的发病机制。据报道，属于醛脱氢酶1（ALDH1A）家族的蛋白质是正常组织干细胞和癌症干细胞的标志物。在本研究中，我们通过免疫组织化学方法检测了ALDH1A同工酶在人类子宫内膜组织（包括受子宫内膜异位症影响的组织）以及卵巢子宫内膜异位囊肿中的表达情况。在子宫内膜基质和卵巢子宫内膜异位组织中观察到了ALDH1A同工酶的阳性染色。在腺体中，不同ALDH1A同工酶的表达模式有所不同。无论月经周期如何，ALDH1A1和ALDH1A3在子宫内膜基底层上皮和卵巢子宫内膜异位囊肿上皮中均高表达，而ALDH1A2仅在子宫内膜异位囊肿上皮中高表达。此外，在基底层腺体中，ALDH1A1与作为子宫内膜上皮祖细胞标志物的N-钙黏蛋白共定位。这些发现支持并强化了关于在子宫内膜基底层腺体和子宫内膜异位腺体中存在祖细胞/干细胞的观点，表明这些细胞参与了子宫内膜的生理过程以及子宫内膜异位症的病理过程。
