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

Abstract

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.

5-Hydroxymethylcytosine profiles in circulating cell-free DNA serve as potential biomarkers for diagnosis and classification of adenomyosis

“…DhMGs may be related to adenomyosis and other gynecological diseases. At the same time, the protein interaction network (Figure 2C-D) showed that these genes including JAK2 that regulate macrophages, CDC42 that regulate cell morphological migration, MAPK1 that participate in immunomodulation, EGFR activation, and cell proliferation, HIF1A that participate in energy metabolism and activating gene transcription, and ITGB1 that participate in cell repair and metastasis [47][48][49][50][51][52] , are signi cantly related to the molecular mechanism and clinical symptoms of adenomyosis.…”

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen–Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations

“…Additionally, the intrauterine microenvironment, provided mostly by glandular secretions, is crucial for implantation. Certain inflammatory conditions, such as adenomyosis or polycystic ovarian syndrome, induce an aberrant implantation process, reducing the pregnancy rate [6,7]. Pituitary suppression with a GnRH agonist before embryo transfer could suppress the hypothalamic-pituitary-gonadal axis and theoretically create better endometrial-embryonic synchronization and microenvironment for fertilization.…”