Anterior Gradient Protein 3 and S100 Calcium-Binding Protein P Levels in Different Endometrial Epithelial Compartments May Play an Important Role in Recurrent Pregnancy Failure.
Recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) are distressing conditions without effective treatments. The luminal epithelium (LE) is integral in determining receptivity of the endometrium, whereas functionalis glands and stroma aid in nurturing early embryo development. Calcium signalling pathways are known to be of vital importance to embryo implantation and pregnancy establishment, and anterior gradient protein 3 (AGR3) and S100 calcium-binding protein P (S100P) are involved with these pathways. We initially examined 20 full-thickness endometrial biopsies from premenopausal women across the menstrual cycle to characterize levels of AGR3 protein in each endometrial sub-region at the cellular level. A further 53 endometrial pipelle biopsies collected in the window of implantation were subsequently assessed to determine differential endometrial AGR3 and S100P levels relevant to RIF (n = 13) and RPL (n = 10) in comparison with parous women (n = 30) using immunohistochemistry. Significantly higher AGR3 and S100P immunostaining was observed in ciliated cells of the LE of women with recurrent reproductive failure compared with parous women, suggesting aberrant subcellular location-associated pathophysiology for these conditions. The nuclear localisation of S100P may allow transcriptional regulatory function, which is necessary for implantation of a viable pregnancy. Further work is thus warranted to assess their utility as diagnostic/therapeutic targets.
['Tempest|Nicola|N|0000-0003-3633-1592', 'Batchelor|Elizabeth|E|', 'Hill|Christopher J|CJ|', 'Al-Lamee|Hannan|H|', 'Drury|Josephine|J|0000-0002-2275-6664', 'Drakeley|Andrew J|AJ|0000-0002-8802-4706', 'Hapangama|Dharani K|DK|0000-0003-0270-0150']
D000026:Abortion, Habitual D000328:Adult D002135:Calcium-Binding Proteins D002352:Carrier Proteins D003656:Decidua D005260:Female D005786:Gene Expression Regulation D006801:Humans D007150:Immunohistochemistry D008597:Menstrual Cycle D008875:Middle Aged D008954:Models, Biological D009363:Neoplasm Proteins D011247:Pregnancy
AGR3 S100P window of implantation reproduction fertility