Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin a...Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.展开更多
Background:The lysosphingolipid,sphingosine-1-phosphate,is a well-described and potent pro-angiogenic factor.Receptors,as well as the sphingosine phosphorylating enzyme sphingosine kinase 1,are expressed in the placen...Background:The lysosphingolipid,sphingosine-1-phosphate,is a well-described and potent pro-angiogenic factor.Receptors,as well as the sphingosine phosphorylating enzyme sphingosine kinase 1,are expressed in the placentomes of sheep and the decidua of rodents;however,a function for this signaling pathway during pregnancy has not been established.The objective of this study was to investigate whether sphingosine-1-phosphate promoted angiogenesis within the placentomes of pregnant ewes.Ewes were given daily jugular injections of FTY720(2-amino-2[2-(−4-octylphenyl)ethyl]propate-1,3-diol hydrochloride),an S1P analog.Results:FTY720 infusion from days 30 to 60 of pregnancy did not alter maternal organ weights nor total number or mass of placentomes,but did alter placentome histoarchitecture.Interdigitation of caruncular crypts and cotyledonary villi was decreased,as was the relative area of cotyledonary tissue within placentomes.Also,the percentage of area occupied by cotyledonary villi per unit of placentome was increased,while the thickness of the caruncular capsule was decreased in ewes treated with FTY720.Further,FTY720 infusion decreased the number and density of blood vessels within caruncular tissue near the placentome capsule where the crypts emerge from the capsule.Finally,FTY720 infusion decreased asparagine and glutamine in amniotic fluid and methionine in allantoic fluid,and decreased the crown rump length of day 60 fetuses.Conclusions:While members of the sphingosine-1-phosphate signaling pathway have been characterized within the uteri and placentae of sheep and mice,the present study uses FTY720 to address the influence of S1P signaling on placental development.We present evidence that modulation of the S1P signaling pathway results in the alteration of caruncular vasculature,placentome architecture,abundance of amino acids in allantoic and amniotic fluids,and fetal growth during pregnancy in sheep.The marked morphological changes in placentome histoarchitecture,including alteration in the vasculature,may be relevant to fetal growth and survival.It is somewhat surprising that fetal length was reduced as early as day 60,because fetal growth in sheep is greatest after day 60.The subtle changes observed in the fetuses of ewes exposed to FTY720 may indicate an adaptive response of the fetuses to cope with altered placental morphology.展开更多
基金supported by USDA-NRICGP 98-35203-6337 to FWB.and RCB,NRSA DHHS/NIH 1-F32-HDO 8501 O1A1 to GAJ,USDA-NRI 2006-35203-17199 to GAJ and Kayla J.BaylessUSDA National Institute of Food and Agriculture Research Initiative Competitive Fellowship Grant no.2012-67011-19892 to James W.Frank and GAJ+1 种基金Agriculture and Food Research Initiative Competitive Grant no.2016-67015-24955 from the USDA National Institute of Food and Agriculture to GAJ and FWBNational Institutes of Health Grant 1R21HD071468-01 to GAJ and KJB。
文摘Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the scientific literature, the illustrations in this manuscript are drafted as Viking imagery for entertainment purposes.
基金National Research Initiative Competitive Grant No.2009-35203-05725(KJB and GAJ)Fellowship No.2008-35203-18830(KAD)from the USDA National Institute of Food and Agriculture.
文摘Background:The lysosphingolipid,sphingosine-1-phosphate,is a well-described and potent pro-angiogenic factor.Receptors,as well as the sphingosine phosphorylating enzyme sphingosine kinase 1,are expressed in the placentomes of sheep and the decidua of rodents;however,a function for this signaling pathway during pregnancy has not been established.The objective of this study was to investigate whether sphingosine-1-phosphate promoted angiogenesis within the placentomes of pregnant ewes.Ewes were given daily jugular injections of FTY720(2-amino-2[2-(−4-octylphenyl)ethyl]propate-1,3-diol hydrochloride),an S1P analog.Results:FTY720 infusion from days 30 to 60 of pregnancy did not alter maternal organ weights nor total number or mass of placentomes,but did alter placentome histoarchitecture.Interdigitation of caruncular crypts and cotyledonary villi was decreased,as was the relative area of cotyledonary tissue within placentomes.Also,the percentage of area occupied by cotyledonary villi per unit of placentome was increased,while the thickness of the caruncular capsule was decreased in ewes treated with FTY720.Further,FTY720 infusion decreased the number and density of blood vessels within caruncular tissue near the placentome capsule where the crypts emerge from the capsule.Finally,FTY720 infusion decreased asparagine and glutamine in amniotic fluid and methionine in allantoic fluid,and decreased the crown rump length of day 60 fetuses.Conclusions:While members of the sphingosine-1-phosphate signaling pathway have been characterized within the uteri and placentae of sheep and mice,the present study uses FTY720 to address the influence of S1P signaling on placental development.We present evidence that modulation of the S1P signaling pathway results in the alteration of caruncular vasculature,placentome architecture,abundance of amino acids in allantoic and amniotic fluids,and fetal growth during pregnancy in sheep.The marked morphological changes in placentome histoarchitecture,including alteration in the vasculature,may be relevant to fetal growth and survival.It is somewhat surprising that fetal length was reduced as early as day 60,because fetal growth in sheep is greatest after day 60.The subtle changes observed in the fetuses of ewes exposed to FTY720 may indicate an adaptive response of the fetuses to cope with altered placental morphology.
