Select Nutrients in the Uterine Lumen of Sheep and Pigs Affect Conceptus Development

Abstract

Abstract. Interferon tau (IFNT) is the pregnancy recognition signal from ruminant conceptuses. IFNT also acts with P4 to induce expression of genes for transport of nutrients, such as glucose (Gluc) and arginine (Arg) into the uterine lumen to activate mechanistic mammalian target of rapamycin (MTOR) cell signaling that stimulates proliferation, migration, gene transcription and mRNA translation by conceptus trophectoderm (Tr). In ewes, Arg and Gluc increase significantly in the uterine lumen between Days 10 and 15 of pregnancy due to increased expression of transporters for Gluc (SLC2A1 and SLC5A1) and Arg (SLC7A2B) by uterine epithelia. Arg and Gluc stimulate proliferation, migration and mRNA translation by Tr. Arg increases expression of GTP cyclohydrolase 1 (GCH1) and IFNT mRNAs while Arg and Gluc increase ornithine decarboxylase, nitric oxide synthase 2, and GCH1 mRNAs and proteins by Tr cells. GCH1 is required for synthesis of tetrahydrobiopterin, an essential cofactor for all NOS isoforms. Arg is metabolized to nitric oxide and polyamines that increase proliferation and migration of Tr cells. In pigs, Gluc, Arg, leucine (Leu) and glutamine (Gln) increase in the uterine lumen between Days 12 and 15 of pregnancy due to enhanced expression of transporters for Gluc and amino acids. Transporters for Gluc in porcine uterine LE (SLC2A1) and conceptus trophectoderm (SLC2A2) are abundant. Transporters for glutamate and neutral (SLC1A1, SLC1A4) and cationic (SLC7A1, SLC7A2, SLC7A7, SLC7A9) amino acids are expressed in uterine LE and SLC7A3 mRNA is expressed in conceptus Tr. Arg and Leu increase MTOR cell signaling and proliferation of pig Tr, as do Gluc and fructose. Azaserine, an inhibitor of hexosamine biosynthesis, inhibits effects of Gluc and fructose. Thus, select nutrients in the uterine lumen affect gene transcription and mRNA translation to affect conceptus development. Key words: Amino acids, Fructose, Glucose, Uterus conceptus development (J. Reprod. Dev. 58: [180][181][182][183][184][185][186][187][188] 2012) E stimates of embryonic death loss in mammals range from 20 to 40 percent and two-thirds of these losses occur during the peri-implantation period of pregnancy [1]. Establishment and maintenance of pregnancy requires appropriate development of the conceptus (embryo/fetus and its extra-embryonic membranes) for pregnancy recognition signaling to ensure maintenance of a functional corpus luteum (CL) to secrete progesterone (P4) that is required for an intrauterine environment that supports implantation, placentation and uterine functions essential for successful outcomes of pregnancy [2]. Interactions among the conceptus and uterine cell types, especially luminal (LE), superficial glandular (sGE) and glandular (GE) epithelia and stromal cells (SC), are essential for conceptus development, signaling for maternal recognition of pregnancy, uterine blood flow, water and electrolyte movement, transport of sugars and amino acids into the uterine lumen, as well as secretion of proteins by uterine epithelia...

Effects of systemic progesterone during the early luteal phase on the availabilities of amino acids and glucose in the bovine uterine lumen

“…Arg, Lys and His (all basic amino acids that share the same transport systems) are essential amino acids that cannot be synthesised by blastocysts, but are required during in vitro culture for murine blastocyst development and expansion, suggesting an important role during conceptus development and the establishment of pregnancy (for a review, see Bazer et al 2012). Subsequent studies revealed that Arg or Leu are central to murine blastocyst expansion and further development, initiating signalling pathways (including mammalian target of rapamycin), increasing mRNA expression and production of nitric oxide and polyamines essential for conceptus development and successful pregnancy (Bazer et al 2012). Other studies have demonstrated the importance of Arg during pregnancy.…”

“…Orn is an intermediary in the synthesis of polyamines, derived from the conversion of Arg to Orn by arginase followed by conversion of Orn to polyamines by ornithine decarboxlyase (ODC1), which is essential for embryogenesis and placental development (Fozard et al 1980;Bazer et al 2012). Cys, a member of the functional amino acids (defined as regulators of key metabolic pathways benefiting survival, growth, development, reproduction and health; Wu et al 2009), has been shown to improve the development of porcine blastocysts in vitro (Choe et al 2010).…”

Energy and lipid metabolism gene expression of D18 embryos in dairy cows is related to dam physiological status

“…Histotroph composition has been widely investigated in the ewe (review Ref. 5), but in this species breeding occurs after weaning and is not concomitant with postpartum lipolysis and NEB induced by lactation as seen in postpartum cows. Lipid utilization for energy metabolism was recently demonstrated in early in vitro cultured bovine embryos (77), but there are no data to our knowledge about peri-implantation embryos.…”

Uterine secretome and its modulation in rat (Rattus norvegicus)

“…Uterine luminal fluid samples of sheep, cattle, and pigs have been previously investigated to define adaptation in the uterine microenvironment in response to the presence of the conceptus (Bazer et al 2012). In the present study, gestational UF, collected at the time of embryo attachment, was investigated for its protein complement.…”