Preliminary Study on the Role of Autophagy in Mouse Endometrium during Peri-Implantation

doi:10.12280/gjfckx.20210160

Abstract

Abstract:

Objective:To observe autophagy in mouse endometrium during peri-implantation period.Methods: ICR pregnant mice (n=36) were randomly divided into blank group and embryo implantation disorder model group (each n=18). The model group was prepared with mifepristone. Mice in each group were given normal saline and 6 mice were killed by neck dislocation respectively on the 4th, 5th, 6th day of gestation. The appearance of uterus was observed. The average number of implantation sites was calculated. The protein expression of microtubule associated protein light chain 3 (LC3-Ⅱ) was detected, and autophagosomes in endometrial cells were observed by transmission electron microscope.Results: In control group, there were no obvious bead-like changes in the uterus on the 4th day of gestation(pd4), but that were obvious and evenly distributed on the 5th day of gestation (pd5) and the 6th day of gestation(pd6). There was no obvious bead-like changes in the uterus on pd4 and pd5 in model group, but few and sparsed bead-like changes on pd6. The average number of embryo implantation sites on pd5 and pd6 in control group was higher than that on pd4, and that on pd6 was significantly different compared with that on pd4 (P<0.05). The average number of embryo implantation sites on pd5 and pd6 in model group respectively decreased compared with control group (P<0.05, P<0.01). Both control group and model group showed that the protein expression of LC3-Ⅱ was not significantly different (P>0.05). Under the transmission electron microscope, endometrial cells of control group were intact. The number of autophagosomes in control group on pd5 was decreased, and increased on pd6. Some endometrial cells in model group were necrosis. There were more autophagosomes in model group on pd4 than that in control group, model group on pd5 and pd6.Conclusions: Autophagy participates in and regulates the process of embryo implantation. Abnormal autophagy may destroy the activity and function of endometrial cells, which is harmful to embryo implantation.

Key words: Autophagy, Peri-implantation period, Embryo implantation, Mice,inbred ICR, Endometrium, Blotting, Western

SHEN Meng-meng, LIU Yan-feng, MA Xiao-na, JIA Jing, WANG Zheng, ZHU Qing-wen. Preliminary Study on the Role of Autophagy in Mouse Endometrium during Peri-Implantation[J]. Journal of International Obstetrics and Gynecology, 2021, 48(6): 666-669.

Figures/Tables 4

References 18

[1]	Kondratskyi A, Kondratska K, Skryma R, et al. Ion channels in the regulation of autophagy[J]. Autophagy, 2018,14(1):3-21. doi: 10.1080/15548627.2017.1384887. doi: 10.1080/15548627.2017.1384887 pmid: 28980859
[2]	Wu MY, Song JX, Wang SF, et al. Selective autophagy: The new player in the fight against neurodegenerative diseases?[J]. Brain Res Bull, 2018,137:79-90. doi: 10.1016/j.brainresbull.2017.11.009. doi: 10.1016/j.brainresbull.2017.11.009
[3]	Devis-Jauregui L, Eritja N, Davis ML, et al. Autophagy in the physiological endometrium and cancer[J]. Autophagy, 2021,17(5):1077-1095. doi: 10.1080/15548627.2020.1752548. doi: 10.1080/15548627.2020.1752548
[4]	Choi J, Jo M, Lee E, et al. The role of autophagy in human endometrium[J]. Biol Reprod, 2012,86(3):70. doi: 10.1095/biolreprod.111.096206. doi: 10.1095/biolreprod.111.096206
[5]	谢云凯, 刘威, 白艺璇, 等. 细胞自噬在子宫腺肌病发病机制中作用的研究进展[J]. 国际妇产科学杂志, 2020,47(2):207-211. doi: 10.3969/j.issn.1674-1870.2020.02.022. doi: 10.3969/j.issn.1674-1870.2020.02.022
[6]	Lessey BA, Young SL. What exactly is endometrial receptivity?[J]. Fertil Steril, 2019,111(4):611-617. doi: 10.1016/j.fertnstert.2019.02.009. doi: S0015-0282(19)30120-7 pmid: 30929718
[7]	Yang S, Wang H, Li D, et al. Role of Endometrial Autophagy in Physiological and Pathophysiological Processes[J]. J Cancer, 2019,10(15):3459-3471. doi: 10.7150/jca.31742. doi: 10.7150/jca.31742
[8]	Bedzhov I, Graham SJ, Leung CY, et al. Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo[J]. Philos Trans R Soc Lond B Biol Sci, 2014,369(1657):20130538. doi: 10.1098/rstb.2013.0538. doi: 10.1098/rstb.2013.0538
[9]	Su Y, Zhang JJ, He JL, et al. Endometrial autophagy is essential for embryo implantation during early pregnancy[J]. J Mol Med (Berl), 2020,98(4):555-567. doi: 10.1007/s00109-019-01849-y. doi: 10.1007/s00109-019-01849-y
[10]	Choi S, Shin H, Song H, et al. Suppression of autophagic activation in the mouse uterus by estrogen and progesterone[J]. J Endocrinol, 2014,221(1):39-50. doi: 10.1530/JOE-13-0449. doi: 10.1530/JOE-13-0449
[11]	孙敬霞, 韩向阳. 米非司酮药物流产时绒毛及蜕膜组织的形态学改变[J]. 中国实用妇科与产科杂志, 2000,16(10):597-598. doi: 10.3969/j.issn.1005-2216.2000.10.010. doi: 10.3969/j.issn.1005-2216.2000.10.010
[12]	孙敬霞, 邹恩昌, 韩燕燕, 等. 米非司酮药物流产时绒毛膜及蜕膜组织的超微结构改变[J]. 中国实用妇科与产科杂志, 2001,17(5):293-294. doi: 10.3969/j.issn.1005-2216.2001.05.021. doi: 10.3969/j.issn.1005-2216.2001.05.021
[13]	Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)[J]. Autophagy, 2016,12(1):1-222. doi: 10.1080/15548627.2015.1100356. doi: 10.1080/15548627.2015.1100356 pmid: 26799652
[14]	Liu L, Liao JZ, He XX, et al. The role of autophagy in hepatocellular carcinoma: friend or foe[J]. Oncotarget, 2017,8(34):57707-57722. doi: 10.18632/oncotarget.17202. doi: 10.18632/oncotarget.17202
[15]	单春华, 赵越超, 杨增明. 缺氧诱导因子在哺乳动物生殖的作用[J]. 生殖医学杂志, 2005,14(4):247-251. doi: 10.3969/j.issn.1004-3845.2005.04.016. doi: 10.3969/j.issn.1004-3845.2005.04.016
[16]	Choi JH, Lee HJ, Yang TH, et al. Effects of hypoxia inducible factors-1α on autophagy and invasion of trophoblasts[J]. Clin Exp Reprod Med, 2012,39(2):73-80. doi: 10.5653/cerm.2012.39.2.73. doi: 10.5653/cerm.2012.39.2.73
[17]	Zhou WJ, Zhang J, Yang HL, et al. Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism[J]. Cell Commun Signal, 2019,17(1):99. doi: 10.1186/s12964-019-0412-9. doi: 10.1186/s12964-019-0412-9
[18]	Wei Q, Zhu R, Zhu J, et al. E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells[J]. Oncol Res, 2019,27(7):827-834. doi: 10.3727/096504018X15462920753012. doi: 10.3727/096504018X15462920753012

组别	n	pd4	pd5	pd6	χ²	P
空白组	6	4（0,14.00）	10.50（8.75,12.00）	15.0（11.00,16.25）*	6.38	0.04
模型组	6	0（0,2.00）	3.50（1.50,7.00）	4.5（0.75,6.50）	4.44	1.09
T或Z		-1.074	4.93	6.19
P		0.28	0.01	0.00

组别	n	pd4	pd5	pd6	χ²	P
空白组	6	4（0,14.00）	10.50（8.75,12.00）	15.0（11.00,16.25）*	6.38	0.04
模型组	6	0（0,2.00）	3.50（1.50,7.00）	4.5（0.75,6.50）	4.44	1.09
T或Z		-1.074	4.93	6.19
P		0.28	0.01	0.00