Global gene expression in equine endometrium around the time of maternal recognition of pregnancy

Abstract

The conceptus-maternal communication during the preimplantation period, also known as maternal recognition of pregnancy (MRP), is crucial for the establishment and maintenance of pregnancy. This communication affects the endometrial transcriptome and proteome with subsequent reduction of endometrial pulsatile prostaglandin F2α secretion and the consequent extension of the corpus luteum's lifespan during early pregnancy in the mare. Also, this communication results in the preparation of the uterine environment for implantation. Any alteration of these processes will result in early embryonic death. Therefore, a better understanding of the normal endometrial transcriptomic changes around the time of MRP might be the key to understanding and preventing early embryonic loss. This study aimed to evaluate the endometrial transcriptome from Day 14 (Day 0 = ovulation) of pregnant and non-pregnant (i.e. diestrus) mares. RNA was isolated from pregnant (n=5) and non-pregnant (n=4) endometrial tissue samples. RNA-Seq was performed using Illumina NovaSeq6000 and differentially expressed genes (DEGs) were evaluated using DESeq.2 based upon an FDR<0.05. Our study identified 1193 DEGs (570 upregulated DEGs and 623 downregulated DEGs) in the pregnant endometrium as compared to the non-pregnant endometrium. In the current study, the pregnant endometrium was associated with downregulation (9.6-fold change) of mRNA forprostaglandin-endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2 enzyme; COX2), which encodes for the rate-limiting enzyme in prostaglandin production. Gene ontology analysis of DEGs revealed that these genes were associated with relevant biological processes such as immune response (TNFAIP1, TNF, CXCR2, TNFSF15, IL15, TGFBR3, IL1B, TNFSF9, TLR8), regulation of trophoblast cell proliferation and migration (BOK, LIF, RBM46, TIMP1, CALR, GJA1), embryo growth and development (PTCH1, PTCH2R, DH10, GLI3, SHOX2, ZDBF2, EVX1, GREM2, KLF2, TWIST1), cell adhesion (COL28A1, EGFL6, ITGA3, FN1, NEDD9, LAMC2, RGMB, THBS4, RHOB, SELP, CHL1, CDHR1, MXRA8, FOLR3, NECTIN3), embryo implantation (MMP9 and LIF), placenta development (ADAM19, MAPK14, BIRC3), amino acids transportation (SLC1A1, SLC25A29, SLC36A2, SLC38A2, SLC7A5), steroid biosynthesis and metabolism (SRD5A1, HSD11B2, HSD17B7, CYP20A1), and progesterone receptors (PAQR5, and PGRMC1). Several of the DEGs identified in the current study are known to play a role in controlling endometrial receptivity to the conceptus in species other than the equine. These findings improve our understanding of the molecular changes taking place in equine endometrium around the time of MRP which might help us to understand and forestall early embryonic loss in the future.