The embryo-derived protein PDI is highly conserved among placental mammals and alters the endometrial transcriptome and secretome <i>in vitro</i> across species with differing implantation strategies

Pregnancy establishment in mammals requires a complex sequence of events, including bi-lateral embryo-maternal communication, leading up to implantation. This is the time when most pregnancy loss occurs in mammals (including humans and food production species) and dysregulation in embryo-maternal communication contributes to pregnancy loss. Embryo-derived factors modify the function of the endometrium for pregnancy success. We hypothesise that these previously unexplored conceptus-derived proteins may be involved in altering the function of the endometrium to facilitate early pregnancy events in mammals with different early pregnancy phenotypes. Here, we show that protein disulphide-isomerase (PDI) is a highly conserved protein among mammals and provide evidence for a species-specific role for PDI in endometrial function in mammals with different implantation strategies. We show how PDI alters the endometrial transcriptome in human and bovine in vitro in a species-specific manner and using a microfluidic approach we demonstrate that it alters the secretome capability of the endometrium. We also provide evidence from in vitro assays using human-derived cells that MNS1, a transcript commonly downregulated in response to PDI in human and bovine endometrial epithelial cells, may be involved in the attachment phase of implantation. We propose that the trophoblast-derived protein PDI, is involved in supporting the modulation of the uterine luminal fluid secreted by the endometrium to support conceptus nourishment, and in the process of embryo attachment to the uterine lumen for pregnancy success in mammals.