Uterine environment and conceptus development in ruminants
Bazer, F WKim, JSong, GSatterfield, M CJohnson, G ABurgardt, R CWu, G
Interferon tau (IFNT), the pregnancy recognition signal from trophectoderm cells of ruminant conceptuses abrogates the uterine luteolytic mechanism to ensure maintenance of functional corpora lutea for production of progesterone (P4). IFNT acts in concert with P4 to induce expression of genes for transport and/or secretion of histotroph that includes nutrients such as glucose and arginine that activate the mechanistic target of rapamycin (MTOR) nutrient sensing cell signaling pathway to stimulate proliferation, migration, differentiation and translation of mRNAs essential for growth and development of the conceptus. Arginine, leucine, glutamine and glucose increase in the uterine lumen during the peri-implantation period of pregnancy due to increased expression of their transporters by uterine luminal epithelium (LE) and superficial glandular epithelium (sGE) in response to P4 and IFNT. In day 16 ovine conceptus explant cultures, arginine increases GTP cyclohydrolase 1 mRNA, and IFNT, while arginine and glucose increase ornithine decarboxylase, nitric oxide synthase 2, and GCH1. Arginine can be metabolized to nitric oxide (NO) and polyamines which stimulate proliferation of ovine trophectoderm (oTr) cells. Secreted phosphoprotein 1 (SPP1, also known as osteopontin) in uterine histotroph increases focal adhesion assembly as a prerequisite for adhesion and migration of oTr cells through activation and cross-talk between MTOR, MAPK, and myosin II motor pathways. Glucose, arginine, leucine and glutamine stimulate MTOR signaling, proliferation and mRNA translation by oTr cells. Further, glucose and fructose were equivalent in stimulating proliferation and synthesis of hyaluronic acid via the hexosamine pathway in oTr and pig Tr cells. These mechanisms allow select nutrients and SPP1 to act coordinately to affect synthesis of proteins involved in cell signaling affecting conceptus growth, development, and survival during the peri-implantation period of pregnancy.(AU)
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