Endometrial gland-specific progestagen-associated endometrial protein and cilia gene splicing changes in recurrent pregnancy loss

Endometrial glands are essential for fertility, consisting of ciliated and secretory cells that facilitate a suitable uterine environment for embryo implantation. This study sought to determine whether an endometrial gland-specific transcriptome and splicing profile are altered in women with recurrent pregnancy loss. Our data provide a comprehensive catalogue of cilia and progestagen-associated endometrial protein (PAEP) gene isoforms and relative exon usage in endometrial glands. We report a previously unannotated endometrial gland cilia transcript GALNT11 and its susceptibility to exon skipping. Key endometrial receptivity gene transcripts are also reported to change in endometrial glands of women with recurrent pregnancy loss. The endometrial gland cilia and PAEP targets identified in this study could be used to identify a perturbed endometrium, isolate causes of recurrent pregnancy loss and develop targeted therapies in personalised medicine. LAY SUMMARY: Successful embryo implantation is a trade-off between the lining of the womb which receives an implanting embryo, termed the endometrium, and a good quality embryo. For days 21–24 of the menstrual cycle, the endometrium undergoes changes into a receptive state in which it can receive an implanting embryo. Inappropriate endometrial receptivity is thought to underlie recurrent pregnancy loss. Improving pregnancy success in women with recurrent pregnancy loss requires an increased understanding of the endometrium at the molecular level. Genes contain the instructions for the cell and which genes are turned on or off determine how well it can do its role. We sought to determine a gene expression pattern of human endometrial glands in women with recurrent pregnancy loss (n = 5) vs a control group (n = 5). We identify target genes altered in women with recurrent pregnancy loss. Endometrial gland markers could be used to identify inappropriate endometrial receptivity.