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.
Similar content being viewed by others
References
Afshar Y et al (2012a) Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse. FASEB J Off Pub Fed Am Soc Exp Biol 26:282–294. doi:10.1096/fj.11-184663
Afshar Y, Miele L, Fazleabas AT (2012b) Notch1 is regulated by chorionic gonadotropin and progesterone in endometrial stromal cells and modulates decidualization in primates. Endocrinology 153:2884–2896. doi:10.1210/en.2011-2122
Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776
Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7:678–689. doi:10.1038/nrm2009
Chapman G, Liu L, Sahlgren C, Dahlqvist C, Lendahl U (2006) High levels of Notch signaling down-regulate NUMB and NUMBlike. J Cell Biol 175:535–540. doi:10.1083/jcb.200602009
Chu PW, Wang YP, Chen IC, Pan HM, Wu GJ (2011) Notch 1 signaling pathway effect on implantation competency. Fertil Steril 96:1225–1229. doi:10.1016/j.fertnstert.2011.08.032
Cobellis L et al (2008) The pattern of expression of Notch protein members in normal and pathological endometrium. J Anat 213:464–472. doi:10.1111/j.1469-7580.2008.00963.x
Cuman C, Menkhorst E, Winship A, Van Sinderen M, Osianlis T, Rombauts LJ, Dimitriadis E (2014) Fetal-maternal communication: the role of Notch signalling in embryo implantation. Reproduction 147:R75–R86. doi:10.1530/REP-13-0474
Cuman et al. (2013) Pre-implantation blastocysts release factors that differentially alter endometrial epithelial cell adhesion and gene expression relative to IVF success. Human Reprod 28(5):1161–1171
Dimitriadis E, Menkhorst E, Salamonsen LA, Paiva P (2010) Review: LIF and IL11 in trophoblast-endometrial interactions during the establishment of pregnancy. Placenta 31:99–104. doi:10.1016/j.placenta.2009.12.027
D’Souza B, Miyamoto A, Weinmaster G (2008) The many facets of Notch ligands. Oncogene 27:5148–5167. doi:10.1038/onc.2008.229
Estrach S, Cordes R, Hozumi K, Gossler A, Watt FM (2008) Role of the Notch ligand Delta1 in embryonic and adult mouse epidermis. J Invest Dermatol 128:825–832. doi:10.1038/sj.jid.5701113
Ilagan MX, Kopan R (2007) SnapShot: notch signaling pathway. Cell 128:1246. doi:10.1016/j.cell.2007.03.011
Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233. doi:10.1016/j.cell.2009.03.045
Leong KG, Karsan A (2006) Recent insights into the role of Notch signaling in tumorigenesis. Blood 107:2223–2233. doi:10.1182/blood-2005-08-3329
Marwood M, Visser K, Salamonsen LA, Dimitriadis E (2009) Interleukin-11 and leukemia inhibitory factor regulate the adhesion of endometrial epithelial cells: implications in fertility regulation. Endocrinology 150:2915–2923. doi:10.1210/en.2008-1538
Mikhailik A, Mazella J, Liang S, Tseng L (2009) Notch ligand-dependent gene expression in human endometrial stromal cells. Biochem Biophys Res Commun 388:479–482. doi:10.1016/j.bbrc.2009.07.037
Mitsuhashi Y, Horiuchi A, Miyamoto T, Kashima H, Suzuki A, Shiozawa T (2012) Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells. Histopathology 60:826–837. doi:10.1111/j.1365-2559.2011.04158.x
Murata A et al (2010) A Notch ligand, Delta-like 1 functions as an adhesion molecule for mast cells. J Immunol 185:3905–3912. doi:10.4049/jimmunol.1000195
Noyes R, Hertig A, Rock J (1950) Dating the endometrial biopsy. Fertil Steril 1:3–25
Paiva P, Salamonsen LA, Manuelpillai U, Dimitriadis E (2009) Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation. Biol Reprod 80:302–310. doi:10.1095/biolreprod.108.071415
Pece S, Confalonieri S, RR P, Di Fiore PP (2011) NUMB-ing down cancer by more than just a NOTCH. Biochim Biophys Acta 1815:26–43. doi:10.1016/j.bbcan.2010.10.001
Sahin Z, Acar N, Ozbey O, Ustunel I, Demir R (2011) Distribution of Notch family proteins in intrauterine growth restriction and hypertension complicated human term placentas. Acta Histochem 113:270–276. doi:10.1016/j.acthis.2009.10.006
Salamonsen LA, Nie G, Hannan NJ, Dimitriadis E (2009) Society for reproductive biology founders’ lecture 2009. Preparing fertile soil: the importance of endometrial receptivity. Reprod Fertil Dev 21:923–934. doi:10.1071/RD09145
Acknowledgments
This work was supported by NHMRC (Australia) Project Grant (#1027100) and by the Victorian Government’s Operational Infrastructure Support Program. ED was supported by NHMRC (Australia) Senior Research Fellowship (#550905).
Author information
Authors and Affiliations
Corresponding author
Additional information
Michelle Van Sinderen and Carly Cuman are the co-first authors.
Rights and permissions
About this article
Cite this article
Van Sinderen, M., Cuman, C., Gamage, T. et al. Localisation of the Notch family in the human endometrium of fertile and infertile women. J Mol Hist 45, 697–706 (2014). https://doi.org/10.1007/s10735-014-9587-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-014-9587-y