New insights into human endometrial aminopeptidases in both implantation and menstruation
New insights into human endometrial aminopeptidases in both implantation and menstruation
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DOI：
10.1016/j.bbapap.2019.140332
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发表时间：
2020-02-01
影响因子：
3.2
通讯作者：
Shibata, Kiyosumi
中科院分区：
文献类型：
--
作者：
Mizutani, Shigehiko;Matsumoto, Kunio;Shibata, Kiyosumi
子宫内膜周期包括子宫内膜上皮细胞的增殖，为受精卵着床做准备。随着排卵，子宫内膜分泌营养物质，如肽和氨基酸进入子宫内膜腔。正常月经周期排卵的组织学证据包括子宫内膜上皮细胞中被胎盘亮氨酸氨肽酶（P-Arg）包围的核下糖原空泡。β-葡萄糖转运蛋白（GLUT）4主要参与细胞内葡萄糖转运，对骨骼肌和脂肪组织的葡萄糖摄取至关重要。另一方面，葡萄糖从血液流入子宫内膜上皮细胞主要不是由GLUTs介导的，而是由排卵后同时出现的孕酮介导的。孕酮不仅增加质膜的通透性，而且增加溶酶体膜的通透性，这可能主要涉及葡萄糖内流。孕激素还扩大了排卵后子宫内膜的胞吐作用，排卵后子宫内膜的分泌可能是顶浆分泌和全分泌，这是溶酶体内容物的胞吐作用的增强和夸大。子宫内膜螺旋动脉/小动脉被分化为蜕膜/前蜕膜细胞的子宫内膜基质细胞包围。蜕膜细胞缺乏氨肽酶A（阿帕），可能导致蜕膜细胞区血管紧张素II作用增强，这是由于阿帕降解血管紧张素II的能力丧失。血管紧张素II被认为在着床后胚胎的蜕膜细胞中发挥生长因子样作用，从而促进着床。在没有植入的情况下，血管紧张素II收缩子宫内膜螺旋动脉/小动脉以促进月经。因此，P-CRP和阿帕可能通过调节葡萄糖转运和缩血管肽参与子宫内环境的稳定。
The endometrium cycle involves proliferation of endometrial epithelial cells in preparation for implantation of fertilized ovum. With ovulation, the endometrium secretes nutrients such as peptides and amino acids into the endometrial cavity. The histological evidence of ovulation in normal menstrual cycle includes subnuclear glycogen vacuoles surrounded by placental leucine aminopeptidase (P-LAP) in endometrial epithelial cells. P-LAP is an essentially involved in intracellular trafficking of glucose transporter (GLUT) 4 which is primarily important for glucose uptake in skeletal muscles and fat tissues. On the other hand, glucose influx from blood into endometrial epithelial cells is not mainly mediated by GLUTs, but by coincident appearing progesterone just after ovulation. Progesterone increases permeability of not only plasma membranes, but also lysosomal membranes, and this may be primarily involved in glucose influx. Progesterone also expands the exocytosis in the endometrium after ovulation, and endometrial secretion after ovulation is possibly apocrine and holocrine, which is augmented and exaggerated exocytosis of the lysosomal contents. The endometrial spiral arteries/arterioles are surrounded by endometrial stromal cells which are differentiated into decidual/pre-decidual cells. Decidual cells are devoid of aminopeptidase A (APA), possibly leading to enhancement of Angiotensin-II action in decidual cell area due to loss of its degradation by APA. Angiotensin-II is thought to exert growth-factor-like effects in post-implantation embryos in decidual cells, thereby contributing to implantation. Without implantation, angiotensin-II constricts the endometrial spiral arteries/arterioles to promote menstruation. Thus, P-LAP and APA may be involved in homeostasis in uterus via regulating glucose transport and vasoconstrictive peptides.