Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

Abstract

Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy recognition signal, and initiates implantation. Blastocyst growth and development requires secretions from the uterine endometrium. An early increase in circulating concentrations of progesterone (P4) stimulates blastocyst growth and elongation in ruminants. This study utilized sheep as a model to identify candidate genes and regulatory networks in the endometrium that govern preimplantation blastocyst growth and development. Ewes were treated daily with either P4 or corn oil vehicle from day 1.5 after mating to either day 9 or day 12 of pregnancy when endometrium was obtained by hysterectomy. Microarray analyses revealed many differentially expressed genes in the endometria affected by day of pregnancy and early P4 treatment. In situ hybridization analyses revealed that many differentially expressed genes were expressed in a cell-specific manner within the endometrium. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify functional groups of genes and biological processes in the endometrium that are associated with growth and development of preimplantation blastocysts. Notably, biological processes affected by day of pregnancy and/or early P4 treatment included lipid biosynthesis and metabolism, angiogenesis, transport, extracellular space, defense and inflammatory response, proteolysis, amino acid transport and metabolism, and hormone metabolism. This transcriptomic data provides novel insights into the biology of endometrial function and preimplantation blastocyst growth and development in sheep.

Endometrial expression of progesterone-induced blocking factor and galectins-1, -3, -9, and -3 binding protein in the luteal phase and early pregnancy in cattle

“…Data in the literature indicate that both beef heifers and dairy cows (with the confounding effects associated with these animal models) display a linear and quadratic relationship between concentrations of progesterone in the early luteal phase (up to day 7) and the subsequent probability of embryo survival/calving rate. In addition, data in both beef heifers (using this animal model) and sheep have shown that supplementation of exogenous progesterone concentrations significantly alters the expression of genes in the endometrium resulting in enhanced conceptus elongation (8,47). Available evidence indicates that progesterone or IFNT alone, or working in concert, can alter the expression of genes in the endometrium; however, a number of genes that are modulated in the uterine endometrium during early pregnancy occur due to the actions of IFNT alone (16,50).…”

Transcriptomic Analysis of the Bovine Endometrium: What is Required to Establish Uterine Receptivity to Implantation in Cattle ?

“…Considerable evidence in the literature has demonstrated that elevated concentrations of circulating progesterone in the immediate post-conception period are associated with advanced conceptus elongation [46,55,56], increased IFNT production [57,58] and higher pregnancy rates in cattle and sheep [59][60][61] with a converse effect on pregnancy rates in dairy cows when progesterone concentrations are low in circulation [10]. Our group has recently begun to address the effect of how the endometrium responds to manipulation of progesterone concentrations in vivo and have been using the working hypothesis that when progesterone is altered in circulation, the endometrial transcriptome is changed, which impacts on the composition of the histotroph.…”

Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes

“…The time of onset, absolute concentration and duration of exposure of the uterus to progesterone seem to play causative roles in accelerating or decelerating conceptus development, at least in the cow and sheep [10e12]. The exact mechanism by which progesterone priming of the uterus controls conceptus growth is however unclear, although it appears that lengthening the period of progesterone exposure increases glucose and amino acid transport in ewes, which in turn stimulates conceptus growth and development [13].…”