Secrets of Endometrial Receptivity: Some Are Hidden in Uterine Secretome

Abstract

Problem Endometrium, the innermost mucosal layer of the uterus, serves as a lodge for the embryo in eutherian mammals. The endometrium is constituted of various cell types, and each cell type executes specific functions to facilitate embryo implantation and development. It is well established that the endometrium, despite being non-permissive to the embryo for the major period of a menstrual cycle, is irreplaceable in the scheme of events essential for procreation. However, the embryo, before initiating physical contact with the endometrium, encounters the uterine cavity that remains bathed in uterine fluid. Uterine fluid is an admixture of endometrial secretions, plasma transudates, and oviductal fluid. Uterine fluid components are believed to play important roles in immunosuppression and embryo development during peri-implantation period. Uterine fluid is also involved in defense against pathogens, sperm migration, and lubrication of endometrium. The advent of highthroughput functional genomics tools has created enormous opportunities to investigate the uterine fluid for its protein repertoire and modulation during the receptive phase of an endometrial cycle in animals and humans. Towards this, few investigations have been conducted in recent years. The data obtained using non-targetted functional genomics approaches need to be assimilated with the existing information on specific components of uterine fluid. MethodThis review compiles existing information on the composition of uterine fluid and its significance in endometrial functions and dysfunctions. ResultCollectively, investigations based on targetted and non-targetted approaches have revealed the presence of several cytokines, growth factors, ions, carbohydrates, and steroids, in human uterine fluid. ConclusionDetailed investigations of human uterine fluid, especially directed towards the elucidation of functional relevance of different proteins in uterine fluid, will help identify novel markers of endometrial receptivity and also gain significant insights into the mechanisms underlying unexplained infertility, recurrent pregnancy losses, and other endometrial pathologies.

Downregulation of genes related to immune and inflammatory response in IVF implantation failure cases under controlled ovarian stimulation

“…Additionally, cytokines, chemokines, proteases, antiproteases, growth factors present in the endometrial fluids or secretions have also been found to be important for the maintenance of microenvironment during implantation which helps in endometrium-embryo crosstalk. 30,32 Similarly, in our study, the genes involved in downregulation of immune and inflammatory response-related functions ( 1,8,23 Their downregulation in our study indicates similar results even in COS. 37 In the current study, lower expression of LIF and IL6ST in glandular epithelium and stromal cells was observed in cases compared to controls even on protein level by immunohistochemistry, indicating the significance of these genes in endometrial receptivity, and therefore validates the results by microarray and real time.…”

Meta-analysis identifies candidate key genes in endometrium as predictive biomarkers for clinical pregnancy in IVF

“…Furthermore, we detected the down-regulation in IF patients of genes involved in cell cycle and apoptosis regulation ( Supplementary Table 3 ), indicative of a reduced rate of cell proliferation in endometrium. Additionally, in this meta-analysis, the down-regulation genes in IF patients were also enriched in estradiol response, chemokines, growth factors, which have been found to be important for the maintenance of microenvironment during implantation supporting the endometrium-embryo crosstalk [ 34 , 35 ].…”

“…We used a comprehensive high-quality PPI database downloaded from the InnateDB [ 30 ], which participates in the International Molecular Exchange (IMEx) consortium [ 31 ]. The database was derived by manually curating protein interaction data from published literature and by integrating experimental data from several PPI databases including MINT [ 32 ], IntAct [ 33 ], BIND, BioGRID [ 34 ] and DIP [ 35 ]. The gene networks were visualized using Cytoscape 3.2.0 [ 36 ].…”

DNA Methylation Changes in Endometrium and Correlation with Gene Expression During Ovarian Hyper-stimulation

“…Endometrial alterations in clinical practice are characterized by the endometrial thickness and morphological alterations which require further histological [6] and biochemical investigations [7].…”