RESUMO
Uterus didelphys is a rare congenital abnormality of the reproductive tract. Although it occurs in various species, there are no published reports describing pregnancy outcome in association with this abnormality. Herein we describe a case of successful unilateral singleton pregnancy in a ewe incidentally found to have uterus didelphys during the course of a biomedical research study. The pregnancy was established using assisted reproductive techniques and interrupted in late gestation, at which point the abnormality was identified. Serial ultrasound assessment of foetal biometry revealed a normal foetal growth trajectory. Despite a 45% reduction in placentome number, total placentome weight was near normal secondary to compensatory placentome growth and development. To our knowledge, this is the first detailed report of normal foetal growth in an animal with uterus didelphys and illustrates the ability of the ovine placenta to adapt to a reduced number of placentomes and maintain foetal nutrient supply.
Assuntos
Doenças dos Ovinos/congênito , Doenças Uterinas/congênito , Útero/anormalidades , Animais , Feminino , Gravidez , OvinosRESUMO
The room-temperature longitudinal piezoresistance of n-type and p-type crystalline silicon along selected crystal axes is investigated under uniaxial compressive stresses up to 3 GPa. While the conductance (G) of n-type silicon eventually saturates at ≈ 45% of its zero-stress value (G(0)) in accordance with the charge transfer model, in p-type material G/G(0) increases above a predicted limit of ≈ 4.5 without any significant saturation, even at 3 GPa. Calculation of G/G(0) using ab initio density functional theory reveals that neither G nor the mobility, when properly averaged over the hole distribution, saturate at stresses lower than 3 GPa. The lack of saturation has important consequences for strained-silicon technologies.
RESUMO
The giant piezoresistance (PZR) previously reported in silicon nanowires is experimentally investigated in a large number of depleted silicon nano- and microstructures. The resistance is shown to vary strongly with time due to electron and hole trapping at the sample surfaces independent of the applied stress. Importantly, this time-varying resistance manifests itself as an apparent giant PZR identical to that reported elsewhere. By modulating the applied stress in time, the true PZR of the structures is found to be comparable with that of bulk silicon.
RESUMO
Uterine blood flow (UtBF) is a major regulator of transplacental fetal nutrient supply. The aim was to serially measure uterine blood flow from mid to late pregnancy in a paradigm of relatively late onset placental and fetal growth restriction. Singleton bearing adolescent dams was fed high (H) or control (C) nutrient intakes to induce putatively compromised or normal pregnancies, respectively. A perivascular flow probe was attached to the uterine artery of the gravid horn on Day 83 of gestation and UtBF was then recorded continuously for 2h, three times weekly until approximately Day 135, when pregnancies were either terminated or ewes allowed to deliver at term (approximately Day 145). Pregnancy outcome was determined at term in contemporaneous ewes without UtBF assessment. Placental and fetal weights were lower (P<0.001) in H compared with C intake groups and were independent of flow probe surgery and monitoring. Uterine blood flow was lower in H compared with C groups at the first assessment (Day 88, P<0.001) and was positively correlated with adjusted fetal weight at term, irrespective of treatment group (P<0.01). UtBF increased throughout the second half of gestation in both groups. Linear regression analysis of UtBF against day of gestation revealed that the slope was equivalent (5.5 vs. 5.3ml/min per day) and the mean intercept lower (212 vs. 370ml/min, P<0.001) in H compared with C groups, respectively. This study demonstrates the feasibility of serially measuring UtBF within the same individual sheep for a protracted period during the second half of gestation. UtBF was already lower at mid gestation in putatively growth restricted compared with control pregnancies, ahead of any reduction in placental and fetal weight, but increased similarly during the second half of gestation in both groups. These data are commensurate with the reported decrease in placental angiogenic growth factor expression at mid gestation, and, indicate that attenuated UtBF is an early defect in this adolescent paradigm.
Assuntos
Retardo do Crescimento Fetal/patologia , Idade Gestacional , Hipernutrição/patologia , Útero/irrigação sanguínea , Fatores Etários , Animais , Peso Corporal/fisiologia , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Masculino , Hipernutrição/complicações , Gravidez , Resultado da Gravidez , Fluxo Sanguíneo Regional , Projetos de Pesquisa , Carneiro Doméstico , Nascimento a Termo , Útero/patologiaRESUMO
The risks of miscarriage, prematurity and low birth weight are particularly acute in adolescent girls who are still growing at the time of conception. The role of maternal nutrition in mediating pregnancy outcome in this vulnerable group has been examined in sheep models. When singleton bearing adolescent dams are overnourished to promote rapid maternal growth throughout pregnancy, growth of both the placenta and fetus is impaired, and birth occurs prematurely relative to control adolescents of equivalent age. Studies at mid-gestation, prior to alterations in placental mass, suggest that reduced proliferation of the fetal trophectoderm, impaired angiogenesis, and attenuated uteroplacental blood flows are early defects in placental development. By late pregnancy, relative placental mass is reduced by 45% but uteroplacental metabolism and placental glucose transfer capacity remain normal when expressed on a placental weight specific basis. The asymmetrically growth-restricted fetuses are hypoxic, hypoglycemic and have reduced insulin and IGF-1 concentrations. Absolute umbilical nutrient uptakes are attenuated but fetal utilisation of glucose, oxygen and amino acids remains normal on a fetal weight basis. This suggests altered sensitivities to metabolic signals and may have implications for subsequent metabolic health. At the other end of the nutritional spectrum, many girls who become pregnant have inadequate or marginal nutritional status during pregnancy. This situation is replicated in a second model whereby dams are prevented from growing during pregnancy by relatively underfeeding. Limiting maternal intake in this way gradually depletes maternal body reserves leading to a lower transplacental glucose gradient and a modest slowing of fetal growth in late pregnancy. These changes appear to be independent of alterations in placental growth per se. Thus, while the underlying mechanisms differ, maternal intake at both ends of the nutritional spectrum is a powerful determinant of fetal growth in pregnant adolescents.
Assuntos
Desenvolvimento Fetal , Fenômenos Fisiológicos da Nutrição Materna , Resultado da Gravidez , Gravidez na Adolescência/fisiologia , Adolescente , Fenômenos Fisiológicos da Nutrição Animal , Animais , Feminino , Retardo do Crescimento Fetal , Humanos , Desnutrição , Modelos Animais , Placenta/irrigação sanguínea , Placenta/fisiologia , Gravidez , Ovinos , Comportamento Social , Útero/irrigação sanguíneaRESUMO
Hydrogen exchange results for cytochrome c have been interpreted in terms of transient hydrogen bond-breaking reactions that include large unfolding reactions and small fluctuational distortions. The differential sensitivity of these opening reactions to denaturant, temperature, and protein stability makes it possible to distinguish the different opening reactions and to characterize their structural and thermodynamic parameters. The partially unfolded forms (PUFs) observed are few and discrete, evidently because they are produced by the reversible unfolding of the protein's several intrinsically cooperative secondary structural elements. The PUFs are robust, evidently because the structural elements do not change over a wide range of conditions. The discrete nature of the PUFs and their small number is as expected for classical folding intermediates but not for theoretically derived folding models apparently because the simplified non-protein models usually analyzed in theoretical studies encompass only a single cooperative unit rather than multiple separable units.
Assuntos
Grupo dos Citocromos c/química , Desnaturação Proteica , Modelos Moleculares , Oxirredução , Dobramento de Proteína , Temperatura , TermodinâmicaRESUMO
This study explores the hypothesis that acute under-nutrition in mid-gestation reduces maternal and fetal nutrient status and affects the expression of specific regulators of placental growth and function. Welsh Mountain ewes were fed a concentrate diet plus wheat straw to provide 100% of their maintenance requirements. The concentrate ration of nutrient restricted (NR) ewes was reduced from day (d) 83 of gestation and withdrawn from d85 to d90. At d90, half the ewes (NR m = 7, control n = 8) were euthanased. The remainder (NR n = 9, control n = 9) were fed their maintenance diet until slaughter at d135. Maternal plasma insulin and IGF-I concentrations decreased during nutrient restriction and NEFA concentrations increased. Fetal IGF-I and insulin concentrations were unaltered by maternal diet. Placental VEGF mRNA expression was reduced at d90 (P < 0.05). IGFBP-3 and IGFBP-2 mRNA expression was reduced at d90 (P < 0.05) and d135 (P < 0.05), respectively. Placental weight was significantly lower in NR ewes at d90 (P < 0.05) and the distribution of placentomes shifted towards the everted phenotype at d135 (P < 0.05). Reduced thoracic girth and uterine fluid volume at d90 (P < 0.05) and decreased fetal lung weight at d90 (P < 0.05) and d135 (P < 0.05) suggest spatial limitation of lung expansion. In summary, acute NR in mid-gestation reduced anabolic drive and mobilised lipid stores in the maternal compartment, whilst fetal nutrient status was maintained. This was accompanied by changes in placental VEGF and IGFBP expression. The growth of the fetal lung appears to have been compromised and this may have adverse consequences for subsequent neonatal respiratory function.
Assuntos
Transtornos da Nutrição Fetal/veterinária , Privação de Alimentos , Substâncias de Crescimento/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Avaliação Nutricional , Placenta/metabolismo , Animais , Ácidos Graxos não Esterificados/sangue , Feminino , Transtornos da Nutrição Fetal/metabolismo , Transtornos da Nutrição Fetal/patologia , Idade Gestacional , Substâncias de Crescimento/genética , Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Tamanho do Órgão , Placenta/patologia , Gravidez/sangue , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Ovinos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Adverse nutritional effects on developing foetal hypothalamic appetitive pathways may contribute to programmed hyperphagia and obesity in intra-uterine growth-restricted, low birth weight offspring. In the present study, for the first time, hypothalamic gene expression for primary orexigenic and anorexigenic genes was examined in late gestation ovine foetuses (130 days; term=145 days) whose mothers were undernourished (UN) or well-nourished (C) throughout pregnancy, or transferred from UN to C on day 90 (UN-C). Pregnancies resulted from singleton embryo transfer into adolescent growing ewes. Body weight, carcass fat content and perirenal adipose tissue (PAT) mass were all lower for UN (n=9) than C (n=7) and intermediate for UN-C foetuses (n=6), with no effect of sex. PAT leptin gene expression (by the reverse transcriptase-polymerase chain reaction) was lower in UN than C and UN-C groups, and lower in males than females. Gene expression (by in situ hybridisation with radiolabelled riboprobes) in the arcuate nucleus was greater in UN than C foetuses for neuropeptide Y (NPY), agouti-related peptide (AGRP) and leptin receptor (OBRb) but not different for pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. Gene expression in UN-C foetuses was intermediate for NPY and AGRP and not different from C foetuses for OBRb. Gene expression for NPY, AGRP and OBRb correlated negatively with foetal carcass fat content and with PAT leptin gene expression across all groups. Males had greater mRNA expression for AGRP than females, with NPY and OBRb showing similar trends. Therefore, maternal undernutrition throughout pregnancy increased orexigenic gene expression in the late gestation foetal hypothalamus, and expression levels were largely normalised by improved maternal nutrition in the last third of pregnancy. These findings may have implications for avoiding or correcting prenatal programming of postnatal hyperphagia and obesity.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Hipotálamo/metabolismo , Desnutrição , Ovinos/embriologia , Adiposidade , Animais , Feminino , Hipotálamo/embriologia , Leptina/genéticaRESUMO
Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in â¼ 50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1 methylation was evident (MF (both P<0.001). IGF1 mRNA expression correlated negatively with IGF1 methylation (r=-0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002-0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA methylation, mRNA expression and plasma IGF1 concentrations.
Assuntos
Retardo do Crescimento Fetal/metabolismo , Fator de Crescimento Insulin-Like I/genética , Ovinos/genética , Animais , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Feminino , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , Masculino , Placenta/irrigação sanguínea , Gravidez , RNA Mensageiro/metabolismo , Ovinos/embriologia , Ovinos/metabolismoRESUMO
The exchange of a large number of amide hydrogens in oxidized equine cytochrome c was measured by NMR and compared with structural parameters. Hydrogens known to exchange through local structural fluctuations and through larger unfolding reactions were separately considered. All hydrogens protected from exchange by factors greater than 10(3) are in defined H-bonds, and almost all H-bonded hydrogens including those at the protein surface were measured to exchange slowly. H-exchange rates do not correlate with H-bond strength (length) or crystallographic B factors. It appears that the transient structural fluctuation necessary to bring an exchangeable hydrogen into H-bonding contact with the H-exchange catalyst (OH(-)-ion) involves a fairly large separation of the H-bond donor and acceptor, several angstroms at least, and therefore depends on the relative resistance to distortion of immediately neighboring structure. Accordingly, H-exchange by way of local fluctuational pathways tends to be very slow for hydrogens that are neighbored by tightly anchored structure and for hydrogens that are well buried. The slowing of buried hydrogens may also reflect the need for additional motions that allow solvent access once the protecting H-bond is separated, although it is noteworthy that burial in a protein like cytochrome c does not exceed 4 angstroms. When local fluctuational pathways are very slow, exchange can become dominated by a different category of larger, cooperative, segmental unfolding reactions reaching up to global unfolding.
Assuntos
Grupo dos Citocromos c/química , Animais , Deutério , Cavalos , Hidrogênio , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Movimento (Física) , Conformação Proteica , Solventes , TermodinâmicaRESUMO
Just as exchangeable hydrogens that are controlled by global unfolding can be used to measure thermodynamic parameters at a global level, hydrogens that are exposed to exchange by local unfolding reactions may be used to obtain locally resolved energy parameters. Results with the hemoglobin system demonstrate the ability of HX methods to locate functionally important changes in a protein and to measure the energetic contribution of each. These results offer the promise that HX measurements may be used to delineate, in terms of definable bonds and their energies and interactions, the network of interactions that Hb and other proteins use to produce their various functions.
Assuntos
Hidrogênio/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Cromatografia Líquida de Alta Pressão , Guanidina , Guanidinas/farmacologia , Hemoglobinas/metabolismo , Cinética , Nucleotídeos/metabolismo , Desnaturação Proteica , Dobramento de Proteína , Temperatura , TermodinâmicaRESUMO
DHEA, an adrenocortical steroid, and its sulfate derivative (DHEA-S), have been implicated in many biological functions, including the regulation of bone mass. In this study, we examined whether DHEA/DHEA-S are capable of directly affecting bone cell proliferation and differentiation, and compared this with the effects of, and interaction with, the established bone cell modulating steroid, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Two in vitro models of human osteoblastic cells were used, viz. MG63 osteosarcoma cell line and normal primary osteoblast-like cells (HOB). Our results show that DHEA and DHEA-S failed on their own to exert direct, independent significant effects on the growth and differentiation of human osteoblastic cells, but treating the cells in conjunction with 1,25(OH)2D3 resulted in enhancement of specific A1P activity. Moreover, 1,25(OH)2D3-induced osteocalcin production was potentiated by the adrenal steroids in both cell models. DHEA-S proved in general to be more potent than DHEA. In conclusion, this study shows that the effects of DHEA/DHEA-S on osteoblastic cell growth and differentiation are likely to be mediated via an effect on 1,25(OH)2D3-induced changes in bone cells, suggesting a distinctive role for these steroids in the regulation of bone metabolism.
Assuntos
Calcitriol/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sulfato de Desidroepiandrosterona/farmacologia , Desidroepiandrosterona/farmacologia , Osteoblastos/efeitos dos fármacos , Interações Medicamentosas , Humanos , Osteoblastos/citologia , Esteroides/metabolismo , Células Tumorais CultivadasRESUMO
Some handguns contain built-in safety devices intended to prevent injuries caused by erroneously believing that a handgun is loaded. A loaded chamber indicator indicates the presence of ammunition in the gun; a magazine safety prevents the gun from being fired when the ammunition magazine is removed, even if one round remains in the firing chamber. In our patent search these devices date back to the turn of the century. But on 1998 pistol models, only 11% contained a loaded chamber indicator and 14% had a magazine safety. In our random-digit-dial telephone survey of U.S. adults, 34.8% of poll respondents (incorrectly) thought that a firearm with its ammunition magazine removed could not be shot, or said that they did not know. Some of the 1100 unintentional gun deaths in the U.S. each year might be prevented if the prevalence of these and other safety devices is increased through legislation, litigation, or voluntary manufacturer action.
Assuntos
Segurança de Equipamentos , Armas de Fogo , Patentes como Assunto , Ferimentos por Arma de Fogo/prevenção & controle , Adolescente , Adulto , Desenho de Equipamento , Armas de Fogo/economia , Armas de Fogo/legislação & jurisprudência , Humanos , Masculino , Estados UnidosRESUMO
A "sequential culture step" system was devised to study osteoclast differentiation from newborn porcine bone marrow cells. Nonadherent cells were collected from cultures of bone marrow cells, and subsequently precultured at a low cell density in low-serum medium supplemented with L929-conditioned medium (L9-CM) derived M-CSF/CSF-1. After 4 d, adherent cells mainly composed of M-CSF-dependent macrophage/osteoclast progenitors, but devoid of stromal-like cells, were further cultured in medium supplemented with L9-CM and CM derived from serum-free cultures of fetal rat calvarial bones. This phase was characterized by a rapid induction of mono- and multinucleated (pre)osteoclast-like cells, positive for cytochemical TRAP activity, but negative for nonspecific esterase (NSE) staining. The presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulated osteoclast generation, whereas calcitonin treatment significantly inhibited this process. The osteoclastic nature of the cells was confirmed by the occurrence of extensive, characteristic bone resorption on dentin slices, which was associated with release of type I collagen N-telopeptides from the bone matrix into the culture medium. The presence of a DNA synthesis inhibitor (HU) during the first 3 d of culture completely inhibited osteoclast formation, whereas HU treatment during the last phase did not affect production of multinucleated osteoclast-like cells. Likewise, a specific antibody directed against M-CSF during the first preculture period, completely abolished osteoclast formation. Adding the antibody during the last phase of the culture, however, strongly inhibited multinucleated osteoclast formation, accompanied by a significant increase in a mononuclear TRAP-positive, NSE-positive (osteoclast precursor) cell fraction. These results indicate that M-CSF is essential for progenitor proliferation as well as for (pre)osteoclast maturation and/ or fusion into multinucleated cells, but also suggest that additional soluble (bone-derived) factors are involved as cofactors in the differentiation process to committed mononuclear osteoclast precursors. The porcine marrow culture approach provides a suitable model system to investigate specific soluble osteoclast-inducing factors affecting different stages of osteoclast development.
Assuntos
Células da Medula Óssea/citologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Osteoclastos/citologia , Animais , Animais Recém-Nascidos , Adesão Celular , Linhagem Celular , Meios de Cultura , Fator Estimulador de Colônias de Macrófagos/imunologia , Fator Estimulador de Colônias de Macrófagos/fisiologia , Camundongos , Testes de Neutralização , Ratos , SuínosRESUMO
The effect of an acid or alkali diet was investigated in 14 mature dairy cows during the last 28 days of pregnancy. The acid diet reduced the incidence of parturient hypocalcaemia compared with the alkali diet and was associated with higher blood ionised calcium and plasma chloride concentrations and lower blood pH and acid-base excess before parturition. Plasma 1,25-dihydroxyvitamin D concentrations before parturition were increased by the acid diet but the concentrations of parathyroid hormone and intact 1-86 parathyroid-hormone-related peptide were unaffected. The estimated fractional calcium absorption and calcium mobilisation rate during an ethylenediamine tetraacetic acid infusion were increased by the acid diet 14 days before parturition. Cortical bone remodelling occurred in all the animals during late pregnancy but was particularly evident in the cows given the acid diet. The data suggest that an acid diet ameliorates parturient hypocalcaemia by enhancing calcium mobilisation before parturition by increasing calcium absorption and bone resorption, these increases possibly being mediated by increases in the plasma concentration of 1,25-dihydroxyvitamin D.
Assuntos
Ração Animal , Osso e Ossos/citologia , Calcitriol/sangue , Cálcio/metabolismo , Trabalho de Parto/sangue , Prenhez/fisiologia , Animais , Reabsorção Óssea , Calcificação Fisiológica , Cálcio/sangue , Bovinos , Cloretos/sangue , Dieta , Feminino , Concentração de Íons de Hidrogênio , Magnésio/sangue , Fosfatos/sangue , GravidezRESUMO
Extrinsic safety devices, such as trigger locks, have been central in the recent state discussions on how to reduce firearm injuries. The actual prevalence of handgun locking devices in the consumer market, however, is unknown. This study catalogued the extrinsic safety devices available from handgun dealers and discount retail chains in Milwaukee, WI. We found that all locations studied (n = 13) stock at least 1 type of extrinsic safety device. A total of 21 unique models of safety devices were stocked by the 13 locations, with trigger locks being the most common (n = 9). Other types of devices included lock-boxes (n = 5), cable locks (n = 4), hammer locks (n = 1), barrel locks (n = 1), and a rubber slide strap (n = 1). Handgun owners in the Milwaukee metro area have a selection of extrinsic handgun safety devices available from handgun dealers and discount retailers. However, there does not appear to be a consistent availability on type of device.
Assuntos
Armas de Fogo/normas , Equipamentos de Proteção , Ferimentos por Arma de Fogo/prevenção & controle , Humanos , WisconsinRESUMO
Intra-uterine growth restriction (IUGR) is involved in developmental metabolic programming and here we test the hypothesis that IUGR affects the developing hypothalamic energy balance regulatory pathways in a sex-specific manner. This experiment investigated early postnatal hypothalamic gene expression for six primary leptin- and insulin-sensitive neuropeptides and receptors in male and female IUGR (n = 8 and 9, respectively) and normal (N) birth weight lambs (n = 8 per gender) gestated and suckled by overnourished mothers. IUGR lambs were smaller at birth, had increased fractional growth rates (FGR), lower final body weight (11 weeks) and similar body fat content compared with N lambs, while males had higher final body weight and insulinemia but lower body fat and leptinemia than females. In situ hybridization revealed greater gene expression in the hypothalamic arcuate nucleus at 11 weeks for anorexigenic genes in females and orexigenic genes in males, with no effect of IUGR. Leptinemia correlated with gene expression for neuropeptide Y (NPY, negatively) in both sexes and pro-opiomelanocortin (POMC, positively) in females but with leptin receptor (negatively) only in males. Current FGR for girth correlated negatively with gene expression for NPY in males and POMC in females. Neither IUGR nor gender affected suckling activity (proxy for appetite) assessed at 3 weeks, but final NPY gene expression correlated with suckling weight gain in males. This study has revealed no effect of IUGR on early postnatal hypothalamic energy balance gene expression but a major effect of gender associated with major sex differences in adiposity and leptinemia.
Assuntos
Peso ao Nascer , Metabolismo Energético/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipotálamo/metabolismo , Caracteres Sexuais , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , Animais , Animais Recém-Nascidos , Composição Corporal , Feminino , Hipotálamo/crescimento & desenvolvimento , Leptina/sangue , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Receptor de Insulina/metabolismo , Receptores para Leptina/metabolismo , Carneiro Doméstico , Comportamento de SucçãoRESUMO
When pregnant adolescent sheep are overnourished during pregnancy normal nutrient partitioning priorities to the gravid uterus are altered, leading to impaired placental development and fetal growth restriction. We hypothesized that decreasing dietary intake in overnourished dams during the final third of gestation may reverse this inappropriate nutrient partitioning in favor of the fetus. Adolescent ewes were offered control (C; n = 12) or high (H; n = 20) dietary intakes to induce normal vs. compromised placental development. Ten ewes receiving the H intake were switched to a low intake at d90 of gestation (HL). Between d90 to 130, HL dams lost weight and adiposity, and metabolic hormones and glucose at d130 were less than H and similar to C. In spite of these maternal changes, at d130 fetal bodyweight was equivalent in HL and H groups and â¼20% less than in C. A greater degree of brain sparing was evident in HL fetuses and glucose and insulin concentrations were more perturbed than in H fetuses. Relative to C, placentome weight was reduced by 46 and 32% in H and HL and the fetal:placentome weight ratio was H > HL > C. Placental vascular morphology was largely unaffected by maternal diet during late gestation but mRNA expression of five angiogenic genes was up-regulated in the fetal cotyledon of HL pregnancies, commensurate with blood vessel remodeling. Nevertheless, overfeeding to promote maternal anabolic growth during adolescent pregnancy impairs feto-placental development that cannot be rescued by reducing maternal intake during the final third of gestation.
Assuntos
Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Desenvolvimento Fetal/fisiologia , Hipernutrição/fisiopatologia , Placentação/fisiologia , Animais , Feminino , Expressão Gênica , Hipernutrição/metabolismo , Placenta/metabolismo , Gravidez , Terceiro Trimestre da Gravidez , OvinosRESUMO
Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term=147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H+early GH) or late gestation (H+late GH) (n=6/group). GH increased maternal glycemia for the duration of treatment. H and H+early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H+late GH fetuses, with 40% increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H+early GH and H+late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.