Changes in various endometrial proteins during cloprostenol-induced failure of early pregnancy in mares
Hayes, M AQuinn, B ALillie, B NBienzle, DCôte, OWaelchli, R OBetteridge, K J
Various major proteins in uterine secretions flushed from mares on day 20 of gestation have been identified and related to levels of gene expression in endometrial biopsies. Pregnancy-related changes were determined by comparison with samples from mares on day 20 after being given a luteolytic IM dose of cloprostenol on day 18, and with cycling mares that were not pregnant on days 17-20. Proteins in cell-free uterine flush samples were identified by LC-MS/MS of trypsin- digested peptides. Levels of endometrial expression were estimated from raw signal strength in Agilent 21322 E. caballus expression microarray. In this paper we describe a subset of pregnancy-related endometrial proteins with potential roles in embryonic development and/or mucosal innate immunity. Endometrial proteins that increased greatly during pregnancy included GM2 activator (GM2A), lipocalin 2 (LCN2), stanniocalcin 1 (STC1) and uterine serpin (SERPINA14). Endometrial proteins that decreased in normal pregnancy included secretory phospholipase A2 (sPLA2), secretoglobin 1A1 (SCGB1A1), and vanin 1 (VNN1). Cloprostenol-induced failure of pregnancy resulted in increased endometrial expression of SPLA2, cathepsin L1 (CTSL1), interleukin-1 receptor antagonist (IL1RN), SCGB1A1 epididymal secretory protein E1 (NPC2), connective tissue growth factor (CTGF), retinol binding protein 4 (RBP4), uteroferrin/TRAP5 (ACP5), SERPINA14, annexin A1 (ANXA1), annexin A3 (ANXA3), and vanin 3 (VNN3). Expression of P19 uterocalin (P19) was similarly high in pregnant and non-pregnant endometrium, and virtually undetectable in the yolk-sac wall. High levels of expression of ANXA2, GM2A, NPC2, CTSL1 and RBP4 in both endometrium and yolk-sac wall suggests that these have important roles on both sides of the maternal:conceptus interface. The properties and distribution of GM2A and NPC2 suggest that they are important in the transport of phospholipids and sterols. SPLA2, LCN2, SCGB1A1 and IL1RA have potential roles in mucosal innate immunity but their production is reduced during early pregnancy. These studies provide an inventory of many proteins in the uterine lumen during early pregnancy, and a subset for which local endometrial expression is altered when pregnancy is compromised by cloprostenol-induced luteolysis.(AU)
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