Proteomic Analysis of Uterine Tissues During Peri-Implantation Period in Mice with Experimentally Induced Adenomyosis that Treated with anti-Ngf: Implications for Cell-Cell Adhesion and Metabolic Processes.
Nerve growth factor (NGF) has been verified to be expressed with higher level in adenomyosis uteri, and its neutralizing antibody has a strong inhibitory influence on inflammation. The present study aimed to explore the effect of anti-NGF on the expression of proteins in uteri of mice-induced adenomyosis and assessed its potential role in improving pregnancy rate. In this study, we established a mouse model of adenomyosis and administrated NGF-neutralizing antibody into mice. The mass spectrometry (MS) analysis of the uteri during the implantation window was performed to explore the essential proteins participating in therapy. Besides, embryos of healthy mice were transferred into the uteri to assess the implantation rate. The results of MS analysis demonstrated that 119 proteins were changed in the adenomyosis group compared with control group, and 126 proteins were differentially expressed in the anti-NGF group compared with the adenomyosis group (fold change > 1.5, P < 0.05. After performing cluster analysis using Mfuzz package, we found that a group of proteins participated in cell-cell adhesion and metabolic processes, which were attenuated in the adenomyosis group, while those were successfully recovered by anti-NGF treatment. Western blotting confirmed that the expression levels of integrin alpha-1 (ITGA1), integrin beta-1 (ITGB1), laminin subunit gamma-1 (LAMC1), and creatine kinase M-type (CKM) were decreased in adenomyosis group, whereas those levels were elevated after anti-NGF treatment. Embryo implantation rate in the adenomyosis group was significantly decreased compared with that in the control group (2.31% vs. 26.15%, P < 0.001) and anti-NGF treatment slightly enhanced the embryo implantation rate in mice with experimentally induced adenomyosis (9.23% vs. 2.31%, P = 0.017). Our results revealed that anti-NGF therapy can improve fertility of mice with experimentally induced adenomyosis, possibly through promoting integrin-related proteins.
['Li|Yan|Y|0000-0002-5371-6454', 'Zhang|Dan|D|', 'Jin|Bailing|B|', 'Xia|Lan|L|', 'Zhang|Aijun|A|']
D062788:Adenomyosis D000818:Animals D057134:Antibodies, Neutralizing D015815:Cell Adhesion Molecules D004195:Disease Models, Animal D010064:Embryo Implantation D004624:Embryo Transfer D004734:Energy Metabolism D005260:Female D005298:Fertility D005300:Fertility Agents, Female D007247:Infertility, Female D008810:Mice, Inbred C57BL D008813:Mice, Inbred ICR D020932:Nerve Growth Factor D011247:Pregnancy D060066:Protein Interaction Maps D020543:Proteome D040901:Proteomics D021241:Spectrometry, Mass, Electrospray Ionization D053719:Tandem Mass Spectrometry D014599:Uterus
Adenomyosis NGF-neutralizing antibody Integrin-related proteins Endometrial receptivity Mass spectrometry analysis