RESUMO
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.
Assuntos
Animais , Aminoácidos/análise , Glucose/análise , Nutrientes/análise , Prenhez/fisiologia , Ruminantes/classificaçãoRESUMO
Uterine adenogenesis in the neonate is critical as uterine glands are essential for pregnancy in adult ruminants. The uterus is stimulated by estrogens (E2) and progesterone (P4) that prepare it to respond to biochemical signals from the conceptus (embryo/fetus and placenta). Interferon ta u (IFNT) is responsible for pregnancy recognition and modification of uterine gene expression including sensitivity to placental lactogen and placental growth hormone that stimulate development and gene expression by epithelial cells of uterine glands. P4 is permissive for most actions of IFNT. Novel genes are expressed by uterine luminal and superficial glandular epithelia in response to P4 and IFNT as those cells are in direct contact with conceptus trophectoderm. But, uterine glandular epithelium and stromal cells respond to P4 and IFNT by expressing classical interferon stimulat ed genes. Uterine receptivity to implantation requires loss of expression of receptors for P4 and E2 by uterine epithelia. P4 stimulates P4 receptor-positive st romal cells to express fibroblast growth factor 10 (FGF10) and hepatocyte growth factor (HGF) that act via their re spective receptors on uterine epithelia and trophectoderm to regulate cellular functions and gene expression. FGF10 and IFNT are hypothesized to activate complementary cell signaling pathways that modulate expression of genes for implantation, modify phenotype of uterine stromal cells, silence expression of genes for P4 and E2 receptors, signal pregnancy recognition, suppress genes for immune recognition, alter membrane permeability to enhance conceptus-maternal exchange of factors, increase endometrial vascularity, and activate genes for transport of nutrients into the uterine lumen. Those actions are essential for a successful outcome of pregnancy.
Assuntos
Animais , Estrogênios/análise , Prenhez/fisiologia , Progesterona/análise , Útero/anatomia & histologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Ruminantes/classificaçãoRESUMO
Uterine adenogenesis in the neonate is critical as uterine glands are essential for pregnancy in adult ruminants. The uterus is stimulated by estrogens (E2) and progesterone (P4) that prepare it to respond to biochemical signals from the conceptus (embryo/fetus and placenta). Interferon ta u (IFNT) is responsible for pregnancy recognition and modification of uterine gene expression including sensitivity to placental lactogen and placental growth hormone that stimulate development and gene expression by epithelial cells of uterine glands. P4 is permissive for most actions of IFNT. Novel genes are expressed by uterine luminal and superficial glandular epithelia in response to P4 and IFNT as those cells are in direct contact with conceptus trophectoderm. But, uterine glandular epithelium and stromal cells respond to P4 and IFNT by expressing classical interferon stimulat ed genes. Uterine receptivity to implantation requires loss of expression of receptors for P4 and E2 by uterine epithelia. P4 stimulates P4 receptor-positive st romal cells to express fibroblast growth factor 10 (FGF10) and hepatocyte growth factor (HGF) that act via their re spective receptors on uterine epithelia and trophectoderm to regulate cellular functions and gene expression. FGF10 and IFNT are hypothesized to activate complementary cell signaling pathways that modulate expression of genes for implantation, modify phenotype of uterine stromal cells, silence expression of genes for P4 and E2 receptors, signal pregnancy recognition, suppress genes for immune recognition, alter membrane permeability to enhance conceptus-maternal exchange of factors, increase endometrial vascularity, and activate genes for transport of nutrients into the uterine lumen. Those actions are essential for a successful outcome of pregnancy.(AU)
Assuntos
Animais , Estrogênios/análise , Progesterona/análise , Prenhez/fisiologia , Útero/anatomia & histologia , Ruminantes/classificação , Peptídeos e Proteínas de Sinalização Intercelular/fisiologiaRESUMO
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)
Assuntos
Animais , Nutrientes/análise , Prenhez/fisiologia , Aminoácidos/análise , Glucose/análise , Ruminantes/classificaçãoRESUMO
The objectives of this investigation were to understand transplacental transport of iron by secreted uteroferrin (UF) and haemophagous areas of water buffalo placenta and clarify the role(s) of blood extravasation at the placental-maternal interface. Placentomes and interplacentomal region of 51 placentae at various stages of gestation were fixed, processed for light and transmission electron microscopy, histochemistry and immunohistochemistry. Haemophagous areas were present in placentomes collected between 4 and 10 months of pregnancy. Perl's reaction for ferric iron was negative in placentomes, but positive in endometrial glands. Positive staining for UF indicated areas in which it was being taken up by phagocytosis and/or fluid phase pinocytosis in areolae of the interplacentomal mesenchyme, with little staining in endometrial stroma. Imunohistochemistry detected UF in trophectoderm of haemophagous regions of placentomes and in other parts of the foetal villous tree, but the strongest immunostaining was in the epithelial cells and lumen of uterine glands. Ultrastructural analyses indicated that erythrophagocytosis was occurring and that erythrocytes were present inside cells of the chorion that also contained endocytic vesicles and caveolae. Results of this study indicate that both the haemophagous areas of placentomes and the areolae at the interface between chorion and endometrial glands are important sites for iron transfer from mother to foetal-placental tissues in buffalo throughout pregnancy.