Dynamic changes in messenger RNA profiles of bovine endometrium during the oestrous cycle

Abstract

During the oestrous cycle, the bovine endometrium exhibits characteristic morphological and functional changes, which are mainly induced by progesterone (P4), oestrogens and oxytocin. We studied the response of the endometrium to this changing hormonal environment at the transcriptome level using a custom-made cDNA microarray. Endometrium samples were recovered from Simmental heifers on days 0 (oestrus), 3.5 (metoestrus), 12 (dioestrus) and 18. The latter group was divided into animals with high (late dioestrus) and low P4levels (preoestrus). Significance analysis of microarrays revealed 269 genes exhibiting significant changes in their transcript levels during the oestrous cycle in distinct temporal patterns. Two major types of expression profiles were observed, which showed the highest mRNA levels during the oestrus phase or the highest levels during the luteal phase respectively. A minor group of genes exhibited the highest mRNA levels on day 3.5. Gene ontology (GO) analyses revealed GO categories related to extracellular matrix remodelling, transport, and cell growth and morphogenesis enriched at oestrus, whereas immune response and particular metabolic pathways were overrepresented at dioestrus. Generation of gene interaction networks uncovered the genes possibly involved in endometrial remodelling (e.g. collagen genes,TNC,SPARC,MMP2,MEP1B,TIMP1,TIMP2,HTRA1), regulation of angiogenesis (e.g.ANGPTL2,TEK,NPY,AGT,EPAS1,KLF5 ), regulation of invasive growth (e.g.PCSK5, tight junction proteins,GRP,LGALS1,ANXA2,NOV,PLAT,MET,TDGF1,CST6,ITGB4), cell adhesion (e.g.MUC16,LGALS3BP) and embryo feeding (e.g.SLC1A1,SLC11A2,SLC16A1,SEPP1,ENPP1). Localisation of mRNA expression in the endometrium was analysed forCLDN4,CLDN10,TJP1,PCSK5,MAGED1, andLGALS1.