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Integrins and their potential roles in mammalian pregnancy

Journal of Animal Science and Biotechnology 2024年第1期15卷 1-19页

作者： Gregory A.Johnson Robert C.Burghardt fuller w.bazer Heew.n Seo Joe w.Cain Department of Veterinary Integrative Biosciences School of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843‑4459USA Department of Animal Science College of Agriculture and Life SciencesTexas A&M UniversityCollege StationTX 77843‑2471USA

Integrins are a highly complex family of receptors that, w.en 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 w.thin 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 w.re associated w.th the evolution of multicellularity, being essential for the association of cells w.th 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 w.th 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 w.ll, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review.provides a succinct overview.of integrin structure, ligand binding, and signaling follow.d w.th 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, follow.d 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, w.ereas 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 sc

关键词： Humans Implantation Integrins Pigs Pregnancy Rodents Sheep

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Pregnancy recognition signaling mechanisms in ruminants and pigs

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Journal of Animal Science and Biotechnology 2013年第3期4卷 170-179页

作者： fuller w.bazer Department of Animal Science Texas A&M University College Station 442D Kleberg Center2471 TAMU Texas 77843-2471 USA

Maternal recognition of pregnancy refers to the requirement for the conceptus（embryo and its associated extraembryonic membranes） to produce a hormone that acts on the uterus and/or corpus luteum（CL） to ensure maintenance of a functional CL for production of progesterone;the hormone required for pregnancy in most *** pregnancy recognition signal in primates is chorionic gonadotrophin w.ich acts directly on the CL via luteinizing hormone receptors to ensure maintenance of functional CL during *** ruminants,interferon tau（IFNT） is the pregnancy recognition *** is secreted during the peri-implantation period of pregnancy and acts on uterine epithelia to silence expression of estrogen receptor alpha and oxytocin receptor w.ich abrogates the oxytocin-dependent release of luteolytic pulses of prostaglandin F2-alpha（PGF） by uterine epithelia;therefore,the CL continues to produce progesterone required for *** conceptuses secrete interferon delta and interferon gamma during the peri-implantation period of pregnancy,but there is no evidence that they are involved in pregnancy recognition ***,pig conceptuses secrete abundant amounts of estrogens betw.en Days 11 to 15 of pregnancy required for maternal recognition of ***,likely in concert w.th prolactin,prevents secretion of PGF into the uterine venous drainage（endocrine secretion）,but maintains secretion of PGF into the uterine lumen（exocrine secretion） w.ere it is metabolized to a form that is not *** PGF is sequestered w.thin the uterine lumen and unavailable to induce luteolysis,functional CL are maintained for production of *** addition to effects of chorionic gonadotrophin,IFNT and estrogens to signal pregnancy recognition,these hormones act on uterine epithelia to enhance expression of genes critical for grow.h and development of the conceptus.

关键词： Pregnancy Interferon Tau Estrogen Prostaglandin F2α

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Osteopontin: a leading candidate adhesion molecule for implantation in pigs and sheep

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Journal of Animal Science and Biotechnology 2015年第2期6卷 177-190页

作者： Greg A Johnson Robert C Burghardt fuller w.bazer Department of Veterinary Integrative Biosciences Texas A&M UniversityCollege Station Department of Animal Science Texas A&M UniversityCollege Station

Osteopontin （OPN; also know. as Secreted Phosphoprotein 1, SPP1） is a secreted extra-cellular matrix （ECM） protein that binds to a variety of cell surface integrins to stimulate cell-cell and cell-ECM adhesion and communication. It is generally accepted that OPN interacts w.th apically expressed integrin receptors on the uterine luminal epithelium （LE） and conceptus trophectoderm to attach the conceptus to the uterus for implantation. Research conducted w.th pigs and sheep has significantly advanced understanding of the role（s） of OPN during implantation through exploitation of the prolonged peri-implantation period of pregnancy w.en elongating conceptuses are free w.thin the uterine lumen requiring extensive paracrine signaling betw.en conceptus and endometrium. This is follow.d by a protracted and incremental attachment cascade of trophectoderm to uterine LE during implantation, and development of a true epitheliochorial or synepitheliochorial placenta exhibited by pigs and sheep, respectively. In pigs, implanting conceptuses secrete estrogens w.ich induce the synthesis and secretion of OPN in adjacent uterine LE. OPN then binds to αvβ6 integrin receptors on trophectoderm, and the αvβ3 integrin receptors on uterine LE to bridge conceptus attachment to uterine LE for implantation. In sheep, implanting conceptuses secrete interferon tau that prolongs the lifespan of CL. Progesterone released by CL then induces OPN synthesis and secretion from the endometrial GE into the uterine lumen w.ere OPN binds integrins expressed on trophectoderm （αvβ3） and uterine LE （identity of specific integrins unknow.） to adhere the conceptus to the uterus for implantation. OPN binding to the αvβ3 integrin receptor on ovine trophectoderm cells induces in vitro focal adhesion assembly, a prerequisite for adhesion and migration of trophectoderm, through activation of： 1） P70S6K via crosstalk betw.en FRAP1/MTOR and MAPK pathw.ys; 2） MTOR, PI3K, MAPK3/MAPK1 （Erk1/2） and MAPK14 （p38） signalin

关键词： Implantation Integrins Psteoponti Pigs Sheep

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FTY720, a sphingosine analog, altered placentome histoarchitecture in ew.s.

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畜牧与生物技术杂志(英文版) 2020年第2期

作者： Kathrin A. Dunlap Bryan G. w.ite David w. Erikson M. Carey Satterfield Christiane Pfarrer Guoyao w. fuller w. bazer Robert C. Burghardt Kayla J. Bayless Greg A. Johnson

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Amino acids and mammary gland development:nutritional implications for milk production and neonatal grow.h

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Journal of Animal Science and Biotechnology 2016年第4期7卷 437-458页

作者： Reza Rezaei Zhenlong w. Yongqing Hou fuller w.bazer Guoyao w. Department of Animal Science Texas A&M University State Key Laboratory of Animal Nutrition China Agricultural University Hubei Key Laboratory of Animal Nutritionand Feed Science Hubei Collaborative Innovation Center for AnimalNutrition and Feed SafetyWuhan Polytechnic University

Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal grow.h, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, grow.h hormone, insulin-like grow.h factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the grow.h, development, and health of neonates. Amino acids （AA）, present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins （primarily 13-casein and a-lactalbumin） and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA （leucine, isoleucine and valine） and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones （e.g., prolactin, insulin and glucocorticoids） and the rate of blood flow.across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as w.ll as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Know.edge of AA utilization （including metabolism） by mammary epithelial cells w.ll enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production w.rldw.de.

关键词： Development Health Livestock Mammary gland Milk Neonates Production Sow.

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Integrins and their potential roles in mammalian pregnancy

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畜牧与生物技术杂志(英文版) 2024年第1期

作者： Gregory A.Johnson Robert C.Burghardt fuller w.bazer Heew.n Seo Joe w.Cain

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Development of a surgical procedure for removal of a placentome from a pregnant ew. during gestation

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Journal of Animal Science and Biotechnology 2020年第4期11卷 986-992页

作者： Colleen A.Lambo Ashley K.Edw.rds fuller w.bazer Kathrin Dunlap M.Carey Satterfield Veterinary Physiology and Pharmacology College of Veterinary Medicine and Biomedical Sciences Texas A&M UniversityCollege StationTX 77843USA Department of Animal Science Texas A&M University2471 TAMUCollege StationTX 77843USA.

Background: In recent decades, there has been a grow.ng interest in the impact of insults during pregnancy on postnatal health and disease. It is know. that changes in placental development can impact fetal grow.h and subsequent susceptibility to adult onset diseases;how.ver, a method to collect sufficient placental tissues for both histological and gene expression analyses during gestation w.thout compromising the pregnancy has not been described. The ew. is an established biomedical model for the study of fetal development. Due to its cotyledonary placental type, the sheep has potential for surgical removal of materno-fetal exchange tissues, i.e., placentomes. A novel surgical procedure w.s developed in w.ll-fed control ew.s to excise a single placentome at ***: A follow.up study w.s performed in a cohort of nutrient-restricted ew.s to investigate rapid placental changes in response to undernutrition. The surgery averaged 19 min, and there w.re no viability differences betw.en control and sham ew.s. Nutrient restricted fetuses w.re smaller than controls(4.7 ± 0.1 kg vs. 5.6 ± 0.2 kg;P w.th greater dam w.ight loss(-32.4 ± 1.3 kg vs. 14.2 ± 2.2 kg;P w.ight of sampled placentomes and placentome numbers did not ***: w.th this technique, gestational studies in the sheep model w.ll provide insight into the onset and complexity of changes in gene expression in placentomes resulting from undernutrition(as described in our study),overnutrition, alcohol or substance abuse, and environmental or disease factors of relevance and concern regarding the reproductive health and developmental origins of health and disease in humans and in animals.

关键词： Developmental biology Fetal development IUGR Ovine/sheep Placenta Placental transport

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Select nutrients and their effects on conceptus development in mammals

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Animal Nutrition 2015年第3期1卷 85-95页

作者： fuller w.bazer Xiaoqiu w.ng Greg A.Johnson Guoyao w. Departments of Animal Science Texas A&M University Veterinary Integrative Biosciences Texas A&M University

The dialogue betw.en the mammalian conceptus(embryo/fetus and associated membranes) involves signaling for pregnancy recognition and maintenance of pregnancy during the critical peri-implantation period of pregnancy w.en the stage is set for implantation and placentation that precedes fetal development. Uterine epithelial cells secrete and/or transport a w.de range of molecules, including nutrients,collectively referred to as histotroph that are transported into the fetal-placental vascular system to support grow.h and development of the conceptus. The availability of uterine-derived histotroph has long-term consequences for the health and w.ll-being of the fetus and the prevention of adult onset of metabolic diseases. Histotroph includes numerous amino acids, but arginine plays a particularly important role as a source of nitric oxide and polyamines required for fetal-placental development in rodents, sw.ne and humans through mechanisms that remain to be fully elucidated. Mechanisms w.ereby arginine regulates expression of genes via the mechanistic target of rapamycin cell signaling pathw.ys critical to conceptus development, implantation and placentation are discussed in detail in this review.

关键词： Amino acids Secreted phosphoprotein 1 Pregnancy Interferon tau Conceptus development Trophectoderm

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Uterine biology in pigs and sheep

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Journal of Animal Science and Biotechnology 2012年第3期3卷 109-129页

作者： fuller w.bazer Gw.nhw. Song Jinyoung Kim Kathrin A Dunlap Michael Carey Satterfield Gregory A Johnson Robert C Burghardt Guoyao w. Department of Animal Science 442D Kleberg Center 2471 TAMU Texas A&M University College Station TX 77843-2471 USA Department of Veterinary Integrated Biosciences Texas A&M University College Station TX 77843-2471 USA

There is a dialogue betw.en the developing conceptus （embryo-fetus and associated placental membranes） and maternal uterus w.ich must be established during the peri-implantation period for pregnancy recognition signaling, implantation, regulation of gene expression by uterine epithelial and stromal cells, placentation and exchange of nutrients and gases. The uterus provide a microenvironment in w.ich molecules secreted by uterine epithelia or transported into the uterine lumen represent histotroph required for grow.h and development of the conceptus and receptivity of the uterus to implantation. Pregnancy recognition signaling mechanisms sustain the functional lifespan of the corpora lutea （CL） w.ich produce progesterone, the hormone of pregnancy essential for uterine functions that support implantation and placentation required for a successful outcome of pregnancy. It is w.thin the peri-implantation period that most embryonic deaths occur due to deficiencies attributed to uterine functions or failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. w.th proper placentation, the fetal fluids and fetal membranes each have unique functions to ensure hematotrophic and histotrophic nutrition in support of grow.h and development of the fetus. The endocrine status of the pregnant female and her nutritional status are critical for successful establishment and maintenance of pregnancy. This review.addresses the complexity of key mechanisms that are characteristic of successful reproduction in sheep and pigs and gaps in know.edge that must be the subject of research in order to enhance fertility and reproductive health of livestock species.

关键词： Genes Grow.h factors Interferon stimulated Pregnancy Pregnancy recognition Uterus

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Application of new.biotechnologies for improvements in sw.ne nutrition and pork production

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Journal of Animal Science and Biotechnology 2019年第4期10卷 817-832页

作者： Guoyao w. fuller w.bazer Department of Animal Science and Center for Animal Biotechnology and Genomics Texas A&M University College Station

Meeting the increasing demands for high-quality pork protein requires not only improved diets but also biotechnology-based breeding to generate sw.ne w.th desired production *** can be classified as the cloning of animals w.th identical genetic composition or genetic engineering(via recombinant DNA technology and gene editing)to produce genetically modified animals or *** helps to conserve species and breeds,particularly those w.th excellent biological and economical *** DNA technology combines genetic materials from multiple sources into single cells to generate ***(genome)editing involves the deletion,insertion or silencing of genes to produce:(a)genetically modified pigs w.th important production traits;or(b)microorganisms w.thout an ability to resist antimicrobial *** gene-editing tools include the use of zinc finger nuclease(ZFN),transcription activator-like effector nuclease(TALEN),or clustered regularly interspaced short palindromic repeats-associated nuclease-9(CRISPR/Cas9)as ***,TALEN,or CRISPR/Cas9 components are delivered into target cells through transfection(lipid-based agents,electroporation,nucleofection,or microinjection)or bacteriophages,depending on cell type and *** to the ZFN and TALEN,CRISPR/Cas9 offers greater ease of design and greater flexibility in genetic engineering,but has a higher frequency of off-target *** date,genetically modified pigs have been generated to express bovine grow.h hormone,bacterial phytase,fungal carbohydrases,plant and *** fatty acid desaturases,and uncoupling protein-1;and to lack myostatin,α-1,3-galactosyltransferase,or CD163(a cellular receptor for the"blue ear disease"virus).Biotechnology holds promise in improving the efficiency of sw.ne production and developing alternatives to antibiotics in the future.

关键词： Biotechnology Disease Grow.h Health Meat production Sw.ne

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