Integrins and their potential roles in mammalian pregnancy

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.

Amino acids and mammary gland development:nutritional implications for milk production and neonatal growth

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 growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the growth, 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 well as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Knowledge of AA utilization （including metabolism） by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.

Functional roles of ornithine decarboxylase and arginine decarboxylase during the peri-implantation period of pregnancy in sheep

Background: Polyamines stimulate DNA transcription and m RNA translation for protein synthesis in trophectoderm cells, as well as proliferation and migration of cells; therefore, they are essential for development and survival of conceptuses(embryo/fetus and placenta). The ovine conceptus produces polyamines via classical and non-classical pathways. In the classical pathway, arginine(Arg) is transformed into ornithine, which is then decarboxylated by ornithine decarboxylase(ODC1) to produce putrescine which is the substrate for the production of spermidine and spermine. In the non-classical pathway, Arg is converted to agmatine(Agm) by arginine decarboxylase(ADC), and Agm is converted to putrescine by agmatinase(AGMAT).Methods: Morpholino antisense oligonucleotides(MAOs) were designed and synthesized to inhibit translational initiation of the m RNAs for ODC1 and ADC, in ovine conceptuses.Results: The morphologies of MAO control, MAO-ODC1, and MAO-ADC conceptuses were normal. Double knockdown of ODC1 and ADC(MAO-ODC1:ADC) resulted in two phenotypes of conceptuses; 33% of conceptuses appeared to be morphological y and functional y normal(phenotype a) and 67% of the conceptuses presented an abnormal morphology and functionality(phenotype b). Furthermore, MAO-ODC1:ADC(a) conceptuses had greater tissue concentrations of Agm,putrescine, and spermidine than MAO control conceptuses, while MAO-ODC1:ADC(b) conceptuses only had greater tissue concentrations of Agm. Uterine flushes from ewes with MAO-ODC1:ADC(a) had greater amounts of arginine, aspartate, tyrosine, citrulline, lysine, phenylalanine, isoleucine, leucine, and glutamine, while uterine flushes of ewes with MAO-ODC1:ADC(b) conceptuses had lower amount of putrescine, spermidine, spermine, alanine, aspartate,glutamine, tyrosine, phenylalanine, isoleucine, leucine, and lysine.Conclusions: The double-knockdown of translation of ODC1 and ADC m RNAs was most detrimental to conceptus development and their production of interferon tau(IFNT). Agm, polyamines, amino acids, and adequate secretion of IFNT are critical for establishment and maintenance of pregnancy during the peri-implantation period of gestation in sheep.

Application of new biotechnologies for improvements in swine nutrition and pork production

Meeting the increasing demands for high-quality pork protein requires not only improved diets but also biotechnology-based breeding to generate swine with desired production traits.Biotechnology can be classified as the cloning of animals with identical genetic composition or genetic engineering(via recombinant DNA technology and gene editing)to produce genetically modified animals or microorganisms.Cloning helps to conserve species and breeds,particularly those with excellent biological and economical traits.Recombinant DNA technology combines genetic materials from multiple sources into single cells to generate proteins.Gene(genome)editing involves the deletion,insertion or silencing of genes to produce:(a)genetically modified pigs with important production traits;or(b)microorganisms without an ability to resist antimicrobial substances.Current 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 editors.ZFN,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 plasmid.Compared 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 effects.To date,genetically modified pigs have been generated to express bovine growth hormone,bacterial phytase,fungal carbohydrases,plant and C.elagan 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 swine production and developing alternatives to antibiotics in the future.

Pre-implantation exogenous progesterone and pregnancy in sheep.II.Effects on fetalplacental development and nutrient transporters in late pregnancy

Background:Administration of progesterone(P4)to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy,likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen.This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy.Suffolk ewes(n=35)were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle(CO,n=18)or 25 mg progesterone in CO(P4,n=17)for the first 8 days of pregnancy.All ewes were hysterectomized on day 125 of pregnancy and:1)fetal and placental weights and measurements were recorded;2)endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism;and 3)maternal plasma,fetal plasma,allantoic fluid,and amniotic fluid were analyzed for amino acids,agmatine,polyamines,glucose,and fructose.Results:Treatment of ewes with exogenous P4 did not alter fetal or placental growth,but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid,respectively.Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1,SLC7A2,SLC2A1,AGMAT,and ODC1 in endometria,as well as SLC1A4,SLC2A5,SLC2A8 and ODC1 in placentomes.In addition,AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes,whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.Conclusions:This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy,suggesting a‘programming’effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.

Phosphate,calcium,and vitamin D signaling,transport,and metabolism in the endometria of cyclic ewes

Background Recent evidence suggests important roles for progesterone(P4)and interferon tau in the regulation of calcium,phosphate,and vitamin D signaling in the uteri of pregnant sheep.However,the effects of P4 and estradiol(E2),with respect to the expression of their receptors PGR and ESR1,respectively,in uterine epithelia on mineral signaling during the estrous cycle has not been investigated.Estrous cycles of mature Suffolk ewes were synchronized,prostaglandin F2αwas administered,and ewes were observed for estrus(designated as Day 0)in the presence of vasectomized rams.On Days 1,9,or 14 of the estrous cycle,hysterectomies were performed.Results 25-hydroxyvitamin D was more abundant in plasma from ewes on Day 14 than Day 1(P<0.05).Expression of fibroblast growth factor receptor 2(FGFR2),a disintegrin and metalloprotease 17(ADAM17),and parathyroid hormone-related protein(PTHrP)mRNAs was greater in endometria on Day 9 compared to Days 1 and 14(P<0.01).Similarly,expression of transient receptor potential cation channel subfamily V member 6(TRPV6)mRNA was greater in endometria on Day 9 than Day 1(P<0.05).ATPase plasma membrane Ca^(2+)transporting 4(ATP2B4)and S100 calcium binding protein G(S100G)mRNA expression was greater in endometria on Day 14 than on Days 1 and 9(P<0.01).In contrast,endometrial expression of vitamin D receptor(VDR)mRNA was lower on Days 9 and 14 than Day 1(P<0.01).Expression of klotho(KL)(P<0.05)and cytochrome P450 family 24 subfamily A member 1(CYP24)(P<0.01)mRNAs was lower on Day 14 than Days 1 and 9.ADAM17,FGF23,CYP2R1,CYP27B1,KL,and VDR proteins immunolocalized to the uterine myometrium,blood vessels,and uterine luminal(LE),superficial glandular(sGE),and glandular(GE)epithelia.S100A9 protein was weakly expressed in the uterine myometrium,LE,sGE,and GE.Immunoreactivity of CYP2R1 and KL proteins in uterine LE and sGE was less on Day 1 than on Days 9 and 14.In contrast,S100G protein was expressed exclusively by GE,and immunoreactive S100G protein was less on Day 9.S100A12 protein localized to stromal cells of the uterine stratum spongiosum and blood vessels,but not by uterine epithelial cells.Conclusion Collectively,these results implicate E2,P4,and PGR in the regulation of phosphate,calcium,and vitamin D signaling in cyclic ewes.

精氨酸营养(一):精氨酸族氨基酸在猪营养与生产中的重要作用<上篇>

精氨酸、谷氨酰胺、谷氨酸、脯氨酸、天冬氨酸、天冬酰胺、鸟氨酸和瓜氨酸可在大多数哺乳动物(包括猪)体内通过复杂的器官间代谢进行相互转化。小肠、肾脏和肝脏是这些氨基酸代谢的主要场所,皮质醇则是这些代谢的一个重要调控激素。由于这些氨基酸(除鸟氨酸和瓜氨酸之外)通常大量地存在于植物和动物的组织蛋白中,所以养猪生产者习惯上不大关心猪日粮中精氨酸族氨基酸的添加问题。然而,最近的研究结果表明,这些氨基酸在养分代谢和免疫应答上起着重要的调控作用,从而会影响猪的饲料利用率。精氨酸和谷氨酸就是其中的典型代表,它们具有明确的功能,因此被广泛地应用于猪肉生产中。由瓜氨酸在小肠中合成减少所引起的精氨酸缺乏,是限制哺乳仔猪获得最佳生长性能的主要因素。酶学和代谢学研究结果均表明,对于7～21日龄哺乳仔猪而言,肠上皮细胞线粒体内N-乙酰谷氨酸的生物利用率低下应为通过谷氨酸和脯氨酸合成瓜氨酸受到阻碍负责。因此,无论在日粮中添加精氨酸还是口服N-胺基甲基麸胺酸(N-carbamylglutamate,N-乙酰谷氨酸的一种稳定的代谢类似物)都能提高哺乳仔猪的肌肉蛋白合成率和增重。此外,在早期断奶的仔猪日粮中添加谷氨酸已可防治其小肠萎缩,并且提高了仔猪的生长性能。值得注意的是,在妊娠30～114d的小母猪日粮中添加精氨酸,也会显著地提高产活仔数和窝初生重。大规模地使用饲料级精氨酸和谷氨酰胺为提高全球养猪生产的动物健康和养分利用率展现了广阔的前景。

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

Background: In recent decades, there has been a growing interest in the impact of insults during pregnancy on postnatal health and disease. It is known that changes in placental development can impact fetal growth and subsequent susceptibility to adult onset diseases;however, a method to collect sufficient placental tissues for both histological and gene expression analyses during gestation without compromising the pregnancy has not been described. The ewe 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 was developed in well-fed control ewes to excise a single placentome at mid-gestation.Results: A follow-up study was performed in a cohort of nutrient-restricted ewes to investigate rapid placental changes in response to undernutrition. The surgery averaged 19 min, and there were no viability differences between control and sham ewes. Nutrient restricted fetuses were smaller than controls(4.7 ± 0.1 kg vs. 5.6 ± 0.2 kg;P < 0.05), with greater dam weight loss(-32.4 ± 1.3 kg vs. 14.2 ± 2.2 kg;P < 0.01), and smaller placentomes at necropsy(5.7 ± 0.3 g vs. 7.2 ± 0.9 g;P < 0.05). Weight of sampled placentomes and placentome numbers did not differ.Conclusions: With this technique, gestational studies in the sheep model will 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.

Dietary supplementation with 0.4%L-arginine between days 14 and 30 of gestation enhances NO and polyamine syntheses and water transport in porcine placentae

Background:Most embryonic loss in pigs occurs before d 30 of gestation.Dietary supplementation with L-arginine(Arg) during early gestation can enhance the survival and development of conceptuses(embryo/fetus and its extraembryonic membranes) in gilts.However,the underlying mechanisms remain largely unknown.Methods:Between d 14 and 30 of gestation,each gilt was fed daily 2 kg of a corn-and soybean-meal based diet(12% crude protein) supplemented with either 0.4% Arg(as Arg-HCl) or an isonitrogenous amount of L-alanine(Control).There were 10 gilts per treatment group.On d 30 of gestation,gilts were fed either Arg-HCl or L-alanine 30 min before they were hysterectomized,followed by the collection of placentae,embryos,fetal membranes,and fetal fluids.Amniotic and allantoic fluids were analyzed for nitrite and nitrate [NOx;stable oxidation products of nitric oxide(NO)],polyamines,and amino acids.Placentae were analyzed for syntheses of NO and polyamines,water and amino acid transport,concentrations of amino acid-related metabolites,and the expression of angiogenic factors and aquaporins(AQPs).Results:Compared to the control group,Arg supplementation increased(P < 0.05) the number of viable fetuses by 1.9 per litter,the number and diameter of placental blood vessels(+ 25.9% and + 17.0% respectively),embryonic survival(+ 18.5%),total placental weight(+ 36.5%),the total weight of viable fetuses(+ 33.5%),fetal crown-to-rump length(+ 4.7%),and total allantoic and amniotic fluid volumes(+ 44.6% and + 75.5% respectively).Compared to control gilts,Arg supplementation increased(P < 0.05) placental activities of GTP cyclohydrolase-1(+ 33.1%) and ornithine decarboxylase(+ 29.3%);placental syntheses of NO(+ 26.2%) and polyamines(+ 28.9%);placental concentrations of NOx(+ 22.5%),tetrahydrobiopterin(+ 21.1%),polyamines(+ 20.4%),c AMP(+ 27.7%),and c GMP(+ 24.7%);total amounts of NOx(+ 61.7% to + 96.8%),polyamines(+ 60.7% to + 88.7%),amino acids(+ 39% to + 118%),glucose(+ 60.5% to + 62.6%),and fructose(+ 41.4% to + 57.0%) in fetal fluids;and the placental transport of water(+ 33.9%),Arg(+ 78.4%),glutamine(+ 89.9%),and glycine(+ 89.6%).Furthermore,Arg supplementation increased(P < 0.05) placental m RNA levels for angiogenic factors [VEGFA120(+ 117%),VEGFR1(+ 445%),VEGFR2(+ 373%),PGF(+ 197%),and GCH1(+ 126%)] and AQPs [AQP1(+ 280%),AQP3(+ 137%),AQP5(+ 172%),AQP8(+ 165%),and AQP9(+ 127%)].Conclusion:Supplementing 0.4% Arg to a conventional diet for gilts between d 14 and d 30 of gestation enhanced placental NO and polyamine syntheses,angiogenesis,and water and amino acid transport to improve conceptus development and survival.

Pre-implantation exogenous progesterone and pregnancy in sheep:I.polyamines,nutrient transport,and progestamedins

Background:Administration of exogenous progesterone(P4)to ewes during the pre-implantation period advances conceptus development and implantation.This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development.Pregnant ewes(n=38)were treated with either 25 mg P4 in 1 mL corn oil(P4,n=18)or 1mL corn oil alone(CO,n=20)from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy.Endometrial expression of genes encoding enzymes for synthesis of polyamines,transporters of glucose,arginine,and glycine,as well as progestamedins was determined by RT-qPCR.Results:On day 12 of pregnancy,conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical.The mRNA expression of AZIN2,an arginine decarboxylase,was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy.Expression of FGF10,a progestamedin,was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation.Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy.Conclusions:Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10,which may accelerate proliferation of trophectoderm cells,but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2.Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.

FTY720,a sphingosine analog,altered placentome histoarchitecture in ewes

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.

精氨酸营养(一):精氨酸族氨基酸在猪营养与生产中的重要作用<下篇>

4精氨酸在新生仔猪营养中的作用 4．1精氨酸合成对维持其在哺乳仔猪体内的自动动态平衡所起的关键作用 对于幼龄仔猪来说，精氨酸是一种必需氨基酸（Southern和Baker，1983；Roth等，1995；Urschel等，2006）。虽然精氨酸可经鸟氨酸循环在肝脏中合成，但由于能够快速水解精氨酸的胞质精氨酸酶具有极高的活性（Wu和Morris，1998），使肝脏不能实现精氨酸的净合成（Urschel等，2005）。

Progesterone regulates tissue non-specific alkaline phosphatase(TNSALP)expression and activity in ovine utero-placental tissues

Background Tissue non-specific alkaline phosphatase(TNSALP;encoded by the ALPL gene)has a critical role in the postnatal regulation of p hospliate homeostasis,yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown.This study tested the hypothesis that progesterone(P4)and/or interferon tau(IFNT)regulate TNSALP activity during pregnancy in sheep.Methods In Exp.1,ewes were bred and received daily intramuscular injections of either corn oil vehicle(CO)or 25 mg progesterone in CO(P4)for the first 8 days of pregnancy and were hysterectomized on either Day 9,12,or 125 of gestation.In Exp.2,ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist(RU486)in CO from Days 8 to 15,and twice daily intrauterine injections of either control proteins(CX)or IFNT(25μg/uterine horn/d)from Days 11 to 15(treatment groups:P4+CX;P4+IFNT;RU486+P4+CX;and RU486+P4+IFNT)and were hysterectomized on Day 16.Results In Exp.1,endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12.TNSALP activity appeared greater in the epithelia,stratum compactum stroma,and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12.On Day 125,TNSALP activity localized to uterine epithelial and endothelial cells,independent of P4 treatment.TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes.In Exp.2,endometrial homogenates from ewes administered RU486+P4+CX had lower TNSALP activity those for P4+CX and P4+IFNT ewes.Immunoreactive TNSALP protein appeared greater in the mid-and deep-glandular epithelia in RU486+P4+CX treated ewes as compared to the other treatment groups.Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486+P4+CX compared to the other treatment groups.Conclusions These results suggest that P4,but not IFNT,regulates the expression and activity of TNSALP in uteroplacental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy.

Within-litter variation in birth weight: impact of nutritional status in the sow

Accompanying the beneficial improvement in litter size from genetic selection for high-prolificacy sows, within-litter variation in birth weight has increased with detrimental effects on post-natal growth and survival due to an increase in the proportion of piglets with low birth-weight. Causes of within-litter variation in birth weight include breed characteristics that affect uterine space, ovulation rate, degree of maturation of oocytes, duration of time required for ovulation, interval between ovulation and fertilization, uterine capacity for implantation and placentation, size and efficiency of placental transport of nutrients, communication between conceptus/fetus and maternal systems, as well as nutritional status and environmental influences during gestation. Because these factors contribute to within-litter variation in birth weight, nutritional status of the sow to improve fetal-placental development must focus on the following three important stages in the reproductive cycle： pre-mating or weaning to estrus, early gestation and late gestation. The goal is to increase the homogeneity of development of oocytes and conceptuses, decrease variations in conceptus development during implantation and placentation, and improve birth weights of newborn piglets. Though some progress has been made in nutritional regulation of within-litter variation in the birth weight of piglets, additional studies, with a focus on and insights into molecular mechanisms of reproductive physiology from the aspects of maternal growth and offspring development, as well as their regulation by nutrients provided to the sow, are urgently needed.

Select nutrients and their effects on conceptus development in mammals

The dialogue between 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 when the stage is set for implantation and placentation that precedes fetal development. Uterine epithelial cells secrete and/or transport a wide range of molecules, including nutrients,collectively referred to as histotroph that are transported into the fetal-placental vascular system to support growth and development of the conceptus. The availability of uterine-derived histotroph has long-term consequences for the health and well-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, swine and humans through mechanisms that remain to be fully elucidated. Mechanisms whereby arginine regulates expression of genes via the mechanistic target of rapamycin cell signaling pathways critical to conceptus development, implantation and placentation are discussed in detail in this review.