Localisation of the Notch family in the human endometrium of fertile and infertile women

Abstract

To investigate the spatial and temporal immunolocalisation and staining intensity of the Notch signalling family in endometrium of fertile and infertile women, endometrial biopsies were collected by curettage from 25 fertile women across the menstrual cycle and 10 infertile women in the mid secretory phase of menstrual cycle. Immunohisotchemistry was completed for NOTCH1, -2, -3, -4, cleaved Notch, DLL1, -3, -4, JAGGED1, -2, HES and NUMB and immunostaining intensity measured in both the endometrial glandular and luminal epithelium. NOTCH1 and the ligands DLL1 and JAGGED1 were key proteins displaying increased staining intensity during the receptive phase of the menstrual cycle and dysregulated in infertile endometrium. Conversely, NUMB a negative regulator of Notch signalling was decreased in the mid secretory phase of the menstrual cycle in fertile women and increased with infertility.

Endometrial Stem Cell Markers: Current Concepts and Unresolved Questions

“…Strong cytoplasmic immunostaining for Numb was limited to the epithelial cells and very weak staining was observed in the stroma. Contrasting results have been reported, suggesting either consistent levels across the menstrual cycle [ 114 ] or decreased immuno-expression in the mid secretory phase [ 118 ]. These studies only utilized single technique (IHC) without any secondary confirmatory techniques or functional work [ 114 ].…”

“…This immuno-expression was dynamic in the endometrium, with higher Notch1 in the proliferative phase than in the secretory phase in some studies [ 114 , 117 ], although the reverse was reported in others [ 115 ], while no significant difference was observed between the proliferative phase in pre-menopausal and postmenopausal samples. Interestingly, the maximal staining intensity was seen in the mid secretory receptive phase of the menstrual cycle [ 118 ]. Strong cytoplasmic immunostaining for Numb was limited to the epithelial cells and very weak staining was observed in the stroma.…”

Loss of CDYL Results in Suppression of CTNNB1 and Decreased Endometrial Receptivity

“…Using String and Cytospace online tools, genes in these clusters were mapped into an interaction network ( Figure 4E and Supplementary Figure S2). Strikingly, we found genes including catenin beta 1 (CTNNB1), NOTCH1 (notch receptor 1), and GJA1 (gap junction protein, alpha), which are well-known regulators of endometrial receptivity (Zhang et al, 2012;Van Sinderen et al, 2014;Winterhager and Kidder, 2015;Su et al, 2016;Yu et al, 2017;Zheng et al, 2017), centered in this network. In addition, transcripts of EPHA2 (EPH Receptor A2), IL6ST (Interleukin 6 Signal Transducer), JAG1 (Jagged canonical notch ligand 1), MSX1 (msh homeobox 1), PLA2G4A (phospholipase A2, group IVA), TGFB1 (transforming growth factor beta 1), SPHK1 (sphingosine kinase 1), and VANGL2 (VANGL planar cell polarity protein 2) exhibited > 1.5-fold change of expression (red dot), which have been proved functional in the endometrial receptivity regulation.…”

Differential gene expression during placentation in pregnancies conceived with different fertility treatments compared with spontaneous pregnancies

“…In early pregnancy, the Notch signaling pathway functions through cell-cell interactions to regulate stem cell renewal and differentiation, decidualization, implantation, placentation, and angiogenesis (84). Notch1 protein expression is higher in the mid-secretory (receptive phase) endometrium of fertile women, compared to infertile women (85). Thus, DNER may be important for maternal embryonic/fetal communication leading to appropriate placentation and downregulation of DNER in IVF pregnancies may impact this communication.…”