Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes

Abstract

The endometrium plays a central role among the reproductive tissues in the context of early embryo-maternal communication and pregnancy. It undergoes typical changes during the sexual/oestrous cycle, which are regulated by the ovarian hormones progesterone and oestrogen. To identify the underlying molecular mechanisms we have performed the first holistic screen of transcriptome changes in bovine intercaruncular endometrium at two stages of the cycle -end of day 0 (late oestrus, low progesterone) and day 12 (dioestrus, high progesterone). A combination of subtracted cDNA libraries and cDNA array hybridisation revealed 133 genes showing at least a 2-fold change of their mRNA abundance, 65 with higher levels at oestrus and 68 at dioestrus. Interestingly, genes were identified which showed differential expression between different uterine sections as well. The most prominent example was the UTMP (uterine milk protein) mRNA, which was markedly upregulated in the cranial part of the ipsilateral uterine horn at oestrus. A Gene Ontology classification of the genes with known function characterised the oestrus time by elevated expression of genes, for example related to cell adhesion, cell motility and extracellular matrix and the dioestrus time by higher expression of mRNAs encoding for a variety of enzymes and transport proteins, in particular ion channels. Searching in pathway databases and literature data-mining revealed physiological processes and signalling cascades, e.g. the transforming growth factor-signalling pathway and retinoic acid signalling, which are potentially involved in the regulation of changes of the endometrium during the oestrous cycle.

Maternal-embryo interaction leading up to the initiation of implantation of pregnancy in cattle

“…A variety of studies in cattle, including studies from our own group (Forde et al, 2009 and, evaluated genes expressed in the endometrium of the uterus during selected stages of the oestrous cycle and pregnancy (Bauersachs et al, 2005(Bauersachs et al, , 2006Mitko et al, 2008;MansouriAttia et al, 2009). However, data on gene expression during the post-hatching embryonic stages in cattle are sparse and, apart from a few exceptions, typically deal with candidate genes rather than being global in nature (Ushizawa et al, 2004;Hue et al, 2007;Degrelle et al, 2011).…”

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

“…Conversely, elevation of progesterone concentrations from Day 3.5 post-oestrus resulted in an increase in the size of Day 16 conceptuses (Carter et al 2008). Many comprehensive studies utilising microarray technologies to characterise the changes in the bovine transcriptome that are associated with the oestrous cycle and early pregnancy have been reported (Bauersachs et al 2005(Bauersachs et al , 2008; Klein et al 2006;McNeill et al 2006), providing an insight into the regulators of the events during early conceptus growth.…”

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

“…Furthermore, the mRNA of integrin beta(4) was shown to be upregulated at diestrus as compared to estrus (Bauersachs et al, 2005). Implantation associated changes in bovine uterine expression of integrins were investigated by McIntyre and coworkers (2002).…”

“…To gain knowledge about genes whose expression is regulated by estrogens, Andrade and others (2002) In an additional study they evaluated the differerence in gene expression profiles of epithelial cells from the ipsilateral oviduct at estrus and diestrus (Bauersachs et al, 2004). They furthermore performed a holistic screen of transcriptome changes in bovine intercaruncular endometrium at the day of standing heat and day 12 of the estrous cycle (Bauersachs et al, 2005). Recently, suppression subtractive hybridization and an array of oligonucleotides, respectively was applied to determine genes involved in the early process of embryonic implantation in the rhesus monkey (Sun et al, 2004) and in mice (Yoshioka et al, 2000).…”

“…The gene LY6G6C, lymphocyte antigen 6 complex locus G6C, belongs to the lymphocyte antigen-6 (LY-6) superfamily and its expression in the bovine endometrium is known to be enhanced during the secretory phase of the estrous cycle (Bauersachs et al, 2005). Members of the LY-6 superfamily are cysteine-rich, generally GPI-anchored cell surface proteins, which have definite or putative immune-related roles and are important in leukocyte maturation.…”