Transcriptional Profiling of Equine Endometrium During the Time of Maternal Recognition of Pregnancy1

Abstract

Establishment and maintenance of pregnancy are critically dependent on embryo-maternal communication during the preimplantation period. To gain new insights into this complex process in the horse, transcriptional profiling of Day 13.5 pregnant and cyclic endometrial tissue samples was carried out using custom-designed microarrays. Selected array data were validated using quantitative RT-PCR, and proteins of interest were localized using immunohistochemistry. One hundred and six transcripts were up-regulated, whereas 47 transcripts showed lower expression levels in pregnant mares, that is, were down-regulated in pregnant mares. Half of the genes with known or inferred function are classically regulated by estrogens. Elevated transcript levels were found for genes involved in cell-cell signaling, heat shock response, and secretory proteins, among others. Solute carrier family 36 (proton/amino acid symporter), member 2, SLC36A2, was one of the most highly up-regulated genes, potentially reflecting the nutritional needs of the rapidly developing embryo. Among the genes showing lower expression in pregnant mares, estrogen receptor 1 was of particular interest because of its potential involvement in the initiation of luteolysis in cyclic mares. We hypothesize that either conceptus' estrogens or luteinizing hormone of uterine origin is involved in the observed down-regulation of estrogen receptor 1. Several of the genes identified in the current study are known to play a role in early pregnancy in species other than the horse. Thus, products of these commonly expressed genes likely contain universal activities for controlling endometrial receptivity to the conceptus, whereas other factors play unique roles within specific species in ensuring ongoing corpus luteum function. This is the first systematic study of endometrial transcriptome changes in response to the presence of an embryo during maternal recognition of pregnancy and an important step toward deciphering the embryo-maternal dialogue in equids.

Early Developing Pig Embryos Mediate Their Own Environment in the Maternal Tract

“…When genes that were differentially expressed in our study in the presence of embryos in the uterine horn were grouped into general categories and pathways the largest changes in gene expression were related to signal transduction, cell communication and immune system, which is in agreement with previous reports [11], [16], [17]. Moreover, immune related genes were the most representative of the altered genes in the present study.…”

“…A number of genes and proteins have already been described to be activated in the endometrium when the embryo arrives in the maternal tract [5], [11]. It is apparent that precise recognition of the embryo in the maternal tract is critical for preparation of a suitable environment for implantation, embryonic development and pregnancy [12].…”

Characterization of the Altered Gene Expression Profile in Early Porcine Embryos Generated from Parthenogenesis and Somatic Cell Chromatin Transfer

“…On the other hand, SLC36A2 and ANXA8 showed significant up-regulation during the blastocyst hatching process in PA embryos, but no up-regulation of these two genes were observed in IVV embryos. SLC36A2 (Solute carrier family 36 (proton/amino acid symporter), member 2) mediates the transport of amino and fatty acids, which are critical to early embryonic development [67], [68]. Further work is necessary to determine if this up-regulation of SLC36A2 is compensating for the function of other dysregulated genes in PA embryos and reflecting the increased need for nutrients in the rapidly developing embryos.…”

Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2)

“…Our knowledge of the physiological importance of PAT2 is limited although it seems likely to have roles in amino acid transport in both renal and neuronal tissues [26–28,31,32]. In addition, a recent study examining changes in gene expression in horses during implantation and early pregnancy demonstrates that the SLC36A2 gene is highly upregulated in uterine tissues, perhaps reflecting the increased nutrient demands of the developing conceptus [43]. Understanding the substrate/inhibitor profile of a particular amino acid transporter has a number of potential uses in pathophysiological conditions as amino acid transporters can be utilised to mediate uptake of substrates that will alter cellular function or as a mechanism to deprive cells of essential nutrients [35].…”