Identification of novel candidate factor SNX5 specific for pregnancy failure in Holstein heifers

Abstract Pregnancy loss predominantly occurs during periods between blastocyst hatching and conceptus (embryo plus extraembryonic membranes) implantation to the endometrium in cattle. Insufficient biochemical communication between conceptus and endometrium has been suspected as the primary cause for early embryonic losses. If molecules regulating this communication were identified, molecular mechanisms associated with early pregnancy success or loss could be better understood. To identify novel factors as detection markers of non-pregnant or females undergoing embryonic loss, blood sera from embryo-transferred heifers on day 7 (day 0 = day of estrus) were collected on day 17, 20, or 22, which were subjected to metabolome and global proteome iTRAQ analyses. On each sample, the metabolome analysis partly divided serum components into pregnant or not. In the iTRAQ analysis, heatmap analysis with 25 unique proteins separated into pregnant or not on day 20 or 22. Furthermore, receiver operating characteristic curve (ROC) analysis identified five candidate proteins detecting non-pregnant heifers, of which SNX5 in day 22 sera had the highest area under the curve (AUC), 0.983. We also detected SNX5 in day 22 sera from non-pregnant heifers using western blotting. These results suggest that high SNX5 in day 22 sera could predict early pregnancy loss in heifers.