Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium

• Published in: Drug design, development and therapy Vol. 13; pp. 1855 - 1863
• Main Authors: Chen, Qian, Yu, Feng, Li, Yan, Zhang, Ai-Jun, Zhu, Xiao-Bin
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2019; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Adult; Agonists; Algorithms; Analysis; Biopsy; Cluster Analysis; Clustering; Complement system; complement-mediated immunity; Cytoskeleton; Embryos; endometrial receptivity; Endometrium; Endometrium - drug effects; Endometrium - pathology; Energy metabolism; Fallopian Tube Diseases - drug therapy; Fallopian Tube Diseases - pathology; Female; Fertilization in vitro; Genetic research; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - agonists; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Gonadotropins; Hormone Antagonists - pharmacology; Hormones; Humans; Immunity; In vitro fertilization; Infertility; Medical schools; Menstruation; Original Research; Ovaries; Ovulation; Peptides; Pituitary (anterior); Pituitary hormones; Principal components analysis; Proteins; proteomic profile; Proteomics; Ultrasonic imaging; Variance analysis; China; Germany; complement-mediated immunity; proteomic profile; endometrial receptivity; energy metabolism
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S201871

The two major ovarian-stimulation protocols for in vitro fertilization are gonadotropin-releasing hormone agonist (GnRH-a) protocol or GnRH antagonist (GnRH-ant) protocol; however, comparisons of their relative efficacy remain controversial. Additionally, conflicting data exist regarding their effects on endometrial receptivity. Thus, this study investigated how GnRH-a and GnRH-ant treatments alter the endometrium during the mid-secretory phase. We compared proteomic profiles across human endometrium tissues of mid-secretory phase from normal control humans (n=5), patients treated with GnRH-a (n=5), and patients treated with GnRH-ant (n=5). We identified 2088 proteins, with 362 that exhibited significantly different expression. Fuzzy c-means clustering (FCM) using the M Fuzz algorithm analysis showed that the same 87 proteins changed significantly in both the GnRH-a and GnRH-ant groups compared with those in the control. Moreover, Gene Ontology (GO) analysis showed that, of these 87, downregulated proteins were associated with energy metabolism and upregulated proteins were linked to cytoskeleton maintenance. Upregulated proteins involved in complement-mediated immunity were present in 151 proteins that exhibited significantly different expression in the GnRH-ant group only. We demonstrated that comparative proteomic analysis is useful for accessing endometrial receptivity, which seemed more strongly impaired by GnRH-ant than GnRH-a treatments. Our findings also revealed that energy metabolism and immunity response may be the key biological mechanisms underlying human endometrial receptivity.