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Biomedical subjects

M E Symonds

Publications and source records attributed to M E Symonds.

At least 73 records · Page 4Linked to original sources

Abundance of leptin mRNA in fetal adipose tissue is related to fetal body weight.

Leptin mRNA was measured in adipose tissue of fetal sheep by reverse transcription polymerase chain reaction (RTPCR). Abundance of leptin mRNA relative to beta-actin mRNA in fetal perirenal adipose tissue increased (P<0.02) with gestation, being higher at 144 d (0.73+/-0. 10, n=5) than at 90-91 d (0.40 +/- 0.08, n=6) or 125 d (0.40 +/- 0. 04, n=5) gestation (term approximately 147- 150 d). There was a positive relationship between relative abundance of leptin mRNA (y) and fetal body weight (x) between 90 and 144 d gestation (r(2) =0.27, P<0.01). The slope of the linear dependence of leptin mRNA on fetal weight was 15-fold greater (P<0.001) at 90-91d (y = 2.81x - 1.1, n=6, r(2) =0.71, P<0.025) than between 125-144 d gestation (y = 0.195x - 0.15, n=16, r(2) =0.39, P<0.01). Thus the leptin synthetic capacity of fetal adipose tissue appears to increase in late gestation but this is accompanied by constraint of its sensitivity to fetal body weight. We hypothesise that leptin synthesis in fetal adipose tissue is related to fetal nutrient supply and growth rate.

Actins↗

Influence of thyrotrophin-releasing hormone on thermoregulatory adaptation after birth in near-term lambs delivered by caesarean section.

We investigated the hypothesis that exogenous stimulation with thyrotrophin-releasing hormone (TRH) immediately prior to umbilical cord clamping can improve thermoregulatory adaptation after birth in near-term lambs delivered by Caesarean section. Lambs received an umbilical vein injection of saline +/- TRH (8 microg) prior to cord clamping. The rate of change in colonic temperature and oxygen consumption after birth were not influenced by TRH, but TRH-treated lambs exhibited a greater incidence of shivering compared with controls over the first hour of neonatal life. Two and a half hours after birth, TRH-treated lambs possessed brown adipose tissue (BAT) with a higher thermogenic activity (i.e. GDP binding to mitochondrial protein), but their BAT had a reduced DNA content and they had less hepatic glycogen than control lambs. TRH administration had no effect on iodothyronine 5' deiodinase activity in BAT and liver, or on plasma concentrations of total triiodothyronine, thyroxine, cortisol or free fatty acids. Three TRH-treated but no control lambs, failed to establish continuous breathing, so tissues from these treated lambs together with time-matched controls were sampled 25 min after birth. These 'non-surviving' TRH-treated lambs had very high plasma catecholamine concentrations, but their lung weights were similar to controls. 'Surviving' TRH-treated lambs possessed lungs with less DNA than non-surviving TRH-treated lambs. It is concluded that umbilical vein injection of TRH prior to umbilical cord clamping increases the recruitment of both shivering and non-shivering thermogenesis after birth.

Adaptation, Physiological↗

The influence of acute hypoxia and carotid body denervation on thermoregulation during non-rapid eye movement sleep in the developing lamb.

We investigated the influence of ambient temperature on the thermoregulatory response to hypoxia in developing lambs before (at 4 and 14 days of age) and after (17 and 30 days of age) carotid body denervation (CBD). Lambs were studied during non-rapid eye movement sleep at thermoneutral (23-15 C) and cool (10-5 C) ambient temperatures, during normoxia and acute hypoxia (inspired oxygen content of 13 %). Measurements of oxygen consumption, arterial partial pressures of O2 and CO2, colonic temperature, incidence of shivering and plasma concentrations of thyroid hormones, cortisol, insulin and glucose were made under each condition. Oxygen consumption was higher at cool compared with thermoneutral ambient temperatures and decreased during hypoxia during cooling at all stages. At 4 days of age, only one lamb shivered during cooling in normoxia, but 4 out of 12 lambs shivered during hypoxia and colonic temperature fell, significantly, by 0.2 C. At 14 days, 8 out of 12 lambs shivered during cooling, of which 6 continued to shiver during hypoxia but colonic temperature did not change significantly. Plasma triiodothyronine concentrations increased on cooling at 4 and 14 days, an affect that was inhibited by hypoxia at 4, but not 14 days of age. At 17 days of age, i.e. post-CBD, plasma thyroid hormone concentrations and oxygen consumption were lower during cold exposure compared with intact lambs at 14 days of age. In CBD lambs, imposing further hypoxia resulted in colonic temperature falling 0. 6 C during cooling, with only 2 out of 10 lambs shivering. Plasma glucose and insulin, but not cortisol, concentrations decreased during hypoxia, irrespective of age or CBD. It is concluded that hypoxia has an important influence on metabolism and thermoregulation, which is modulated by age and environmental conditions. Compromised carotid body function, in lambs older than 2 weeks of age, can result in severe hypoxia and thermoregulatory dysfunction even with modest environmental cooling.

Animals↗

Effects of increasing gestation, cortisol and maternal undernutrition on hypothalamic neuropeptide Y expression in the sheep fetus.

We have characterized the localization and the ontogenetic changes in Neuropeptide tyrosine (NPY) before birth and investigated the regulation of NPY expression by cortisol and undernutrition in the fetal sheep hypothalamus during late gestation. Using immunohistochemistry, we have identified NPY-containing neurons in the infundibular nucleus and the internal layer of the median eminence in fetal hypothalami collected between 110 and 147 days gestation. NPY projections were also present in the paraventricular nucleus (PVN) of fetal hypothalami at all ages between 110 days gestation and term. There was a significant increase in the amount of immunoreactive NPY/g hypothalamus between 87 and 113 days and 131-140 days gestation and a further significant increase after 141 days gestation. The total hypothalamic content of immunoreactive NPY increased significantly between 87 and 113 days and 141-145 days gestation. The levels of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus were significantly higher at 145-146 days gestation than at any earlier gestational age between 116 and 141 days gestation. Cortisol (2.5-3.0 mg/24 h) was infused intrafetally between 109 and 116 days gestation. The ratio of NPY mRNA: 18s rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the cortisol-infused group when compared with the saline-infused control group at 116 days gestation. Maternal, and hence fetal undernutrition, was induced between 110 and 146 days gestation. At 145-146 days gestation the ratio of NPY mRNA: 18S rRNA in the mediobasal region of the fetal hypothalamus was significantly higher in the undernutrition group when compared with control animals. We have therefore demonstrated that NPY is present in the hypothalamus of the sheep fetus before birth and that hypothalamic NPY content and NPY mRNA increase before delivery. We have also found that glucocorticoids and undernutrition stimulate increases in NPY mRNA levels in the hypothalamus before birth.

Animals↗

Prolactin receptor gene expression and foetal adipose tissue.

We have investigated the effects of increasing gestational age, maternal undernutrition or restricted placental growth on prolactin receptor (PRLR) gene expression in perirenal adipose tissue collected from foetal sheep during late gestation (term = 147 d +/- 3 d of gestation). Foetal nutrient supply was reduced by either restriction of placental growth following removal of endometrial caruncles before mating or by reducing maternal feed intake by 50% from 115 d of gestation. Total RNA was extracted from adipose tissue taken from foetal sheep between 90 and 145 d of gestation, and only at 141-145 d in placentally restricted, nutrient restricted and control foetuses. Messenger RNAs encoding the long (PRLR1) and short (PRLR2) forms of the PRLR and glyceraldehyde-phosphate-dehydrogenase (GAPDH) were detected and quantified in a ribonuclease protection assay using an antisense RNA probe complementary to ovine PRLR2 and GAPDH. There was a 7.5-fold increase in the amount of perirenal adipose tissue between 90 and 125 d of gestation, compared with a 1.3-fold increase between 125 and 145 d of gestation. The abundance of mRNA encoding PRLR1 and PRLR2 in perirenal adipose tissue increased 10- and sixfold, respectively, between 90 and 125 d of gestation, and then declined by 145 d of gestation. Both placental restriction and maternal undernutrition significantly reduced foetal adipose tissue deposition. The abundance of PRLR1 but not PRLR2 mRNA was reduced in adipose tissue from the placentally restricted group, where as GAPDH mRNA was three times higher than in controls. In contrast, maternal undernutrition from 115 d of gestation did not affect PRLR1, PRLR2 or GAPDH mRNA expression in foetal adipose tissue. It is concluded that during the period of rapid deposition of perirenal adipose tissue, there is a concomitant increase in PRLR gene expression. This indicates that prolactin may play an important role in the growth and maturation of foetal adipose tissue which occurs before birth.

Adipose Tissue↗

Influence of maternal bodyweight on adaptation after birth in near-term lambs delivered by Caesarean section.

The present study investigated the influence of maternal bodyweight on adaptation after birth in near-term lambs delivered by caesarean section. One twin lamb from a heavy (>60 kg) or light ewe (<55 kg) was randomly taken and immediately placed into a warm (30 degrees C) ambient temperature and its twin then delivered into a cool (15 degrees C) ambient temperature. Continuous recordings of colonic temperature were then made followed by measurements of thermoregulation and brown adipose tissue function up to 6 h of life. Following caesarean section delivery colonic temperature rapidly declined over the first 30 min of life, a response that was greater in lambs at 15 degrees C. Irrespective of ambient temperature all lambs born to heavy ewes commenced shivering within 15 min of birth and were able to restore body temperature. These adaptations were only observed in warm-delivered lambs born to light ewes, as cool-delivered lambs failed to shiver, became hypothermic and 4 out of 6 lambs exhibited respiratory failure. Umbilical vein plasma thyroid hormone concentrations were lower in lambs born to light compared with heavy ewes. Plasma T3 concentrations remained lower in warm-delivered lambs born to light ewes until 2 h after birth when heat production and colonic temperature were not significantly different from warm delivered lambs born to heavy ewes. Lambs born to light ewes possessed less brown adipose tissue than those born to heavy ewes. In conclusion, maternal bodyweight has a critical influence on survival following caesarean section birth that is dependent on the ambient temperature into which a lamb is delivered.

Adaptation, Physiological↗

Maternal nutrition in early-mid gestation and placental size in sheep.

We investigated the influence of restricted maternal nutrition between 30 and 80 d gestation on placental growth. Singleton-bearing ewes were fed on either 0.6 (i.e. nutrient restricted) times their energy requirements of 2.25 times this amount (i.e. controls) up to 80 d gestation, when their placentas and fetuses were sampled and analysed. Nutrient-restricted ewes lost body condition score but not body weight and had lower plasma thyroid hormone concentrations than controls, but there were no differences in plasma glucose, non-esterified fatty acids or 3-hydroxybutyrate concentrations between groups. There was no effect of maternal nutrient restriction on fetal weight, conformation or organ weight with the exception of brain weight which was lower nutrient-restricted ewes. Nutrient restriction had no effect on total placental weight, or proportion of inverted placentomes, but was associated with an increased abundance of small placentomes and decreased weight of the fetal but not maternal components of the placenta. Fetal cotyledons form nutrient-restricted ewes also had a lower DNA but higher haemoglobin concentration than those sampled from controls. The plasma concentration of triiodothyronine in umbilical cord plasma was also increased in fetuses from nutrient-restricted ewes. In conclusion, maternal nutrient restriction during early-mid gestation is associated with a smaller placenta.

Animal Nutritional Physiological Phenomena↗

Thermoregulation in newborn lambs: influence of feeding and ambient temperature on brown adipose tissue.

We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of brown adipose tissue (BAT) in newborn lambs maintained at a warm (30 degrees C) ambient temperature. This study further examines the effect of ambient temperature on BAT and thermoregulation by investigating the response to feeding 50 ml of water. Immediately after vaginal birth, lambs were placed in either a warm (30 degrees C) or cool (15 degrees C) environment a ambient temperature and measurements of colonic temperature and heat production were recorded for 6 h. Lambs were fed 50 ml of water when 5 h old. The level of guanosine 5'-diphosphate (GDP) binding was higher, but adrenaline content lower in BAT sampled from lambs maintained at 15 degrees C compared with those at 30 degrees C. Feeding was associated with an increase in colonic temperature and plasma concentrations of glucose and non-esterified fatty acids in lambs maintained at 15 degrees C only. In this group plasma concentrations of adrenaline and dopamine declined after feeding, but noradrenaline concentrations were not influenced by feeding in either group of lambs. O2 consumption and CO2 production were higher in lambs maintained at 15 degrees C but were not influenced by ambient temperature or feeding. It is concluded that feeding a small volume of water can influence thermoregulation by a mechanism that is dependent on the ambient temperature at which the lamb is maintained.

Adipose Tissue, Brown↗

Beta2-agonist ritodrine, unlike natural catecholamines, activates thermogenesis prematurely in fetal sheep.

Prolonged administration of the beta2-adrenergic agonist ritodrine to fetal sheep increases nonesterified fatty acid mobilization. To investigate whether changes in fetal growth or functional development of brown adipose tissue (BAT) also occur, ritodrine was infused at 5 microg/min iv into eight fetal sheep (6 twins and 2 singletons at 125-128 days of gestation) for 5 days and then at twice this rate for a further 7-11 days. Fetal growth was reduced significantly (P < 0.02) during ritodrine infusion relative to controls (5.8 +/- 17.5 vs. 79.7 +/- 10.3 g/day), with growth of skeletal muscles ceasing. Ritodrine reduced perirenal BAT weight by 50% from 18.6 +/- 1.89 to 9.3 +/- 0.60 g (P < 0.01) and its lipid content by >70% from 6.5 +/- 0.96 to 1.9 +/- 0.45 g (P < 0.01). Mitochondrial protein in BAT was also less (P < 0.002), but GDP binding to uncoupling protein increased (P < 0.05). In similar experiments, epinephrine and norepinephrine increased plasma nonesterified fatty acid initially, but neither altered perirenal BAT composition. The beta2-adrenergic agonist ritodrine appears able to promote lipid mobilization and thermogenesis in utero.

Adipose Tissue, Brown↗

Influence of thyrotrophin-releasing hormone on thermoregulation in newborn lambs.

This study examined the effect of thyrotrophin-releasing hormone (TRH) administration on thermoregulation in the newborn. Twin lambs were either delivered near-term by caesarean section or born vaginally at term. Colonic temperature, O2 consumption, CO2 production, breathing and heart rates, plus plasma thyroid hormone and nonesterified fatty acid (NEFA) concentrations and thermogenic activity (i.e. GDP binding) of brown adipose tissue (BAT) were measured. In caesarean section delivered lambs colonic temperature decreased rapidly after birth, a response that was greater in the group designated for TRH treatment, in which colonic temperature fell to below 36.0 degrees C at 80 min of life, prior to TRH administration. At this age colonic temperature had been restored to a mean of 38.70 degrees C in controls. TRH had no influence on the composition or thermogenic activity of BAT. The incidence of shivering was not influenced by TRH, but treated lambs maintained a higher rate of O2 consumption and ventilation compared with controls after colonic temperature had been restored to 38.56 degrees C. TRH appeared to promote fat oxidation as O2 consumption remained unchanged and CO2 production declined by a greater rate in treated lambs, resulting in a lower respiratory quotient compared to controls. Heart rate and plasma concentrations of NEFA increased following TRH administration although this did not result in values greater than controls. Normothermic lambs born vaginally had BAT with a greater thermogenic activity, higher plasma thyroid hormone and NEFA concentrations compared with caesarean section delivered lambs, but a thermogenic response was not observed to TRH despite a rise in thyroid hormone concentrations. In conclusion, TRH can improve thermoregulation, an effect that could be linked to an increase in fat oxidation.

Animals↗

Influence of restricted maternal nutrition in early to mid gestation on placental and fetal development at term in sheep.

We investigated the influence of restricted maternal nutrition between 28 and 77 d of gestation on placental weight and appearance, and on fetal weight and conformation. Single-bearing ewes were fed either twice [i.e. controls (n = 19)] or half [i.e. nutrient-restricted (n = 28)] their energy requirements from 28 to 77 d of gestation, after which all ewes were fed to fully meet the energy requirements for maintenance and pregnancy. Close to term (145 +/- 1 d) placental weight was higher in the nutrient-restricted group [nutrient-restricted, 416.3 +/- 12.6 g; controls, 347.4 +/- 17.6 g (p < 0.01)], as was the abundance of everted placentomes. There was no significant difference in total fetal weight, or weights of individual organs between groups, but crown-rump length was significantly greater in lambs born to nutrient-restricted ewes [nutrient-restricted, 50.4 +/- 0.4 cm; controls, 48.2 +/- 0.6, cm (p < 0.01)]. Fetal to placental weight ratio was lower in the nutrient-restricted group [nutrient-restricted, 9.51 +/- 0.23; controls, 10.81 +/- 0.39 (p < 0.01)]. A stronger relationship between the total weight of the fetal component of the placental and fetal weight was observed in controls (r2 = 0.50) than in nutrient-restricted ewes (r2 = 0.18). In conclusion, maternal nutrient restriction over the period of rapid placental growth results in a larger placenta and altered placental to fetal weight ratio if ewes are subsequently fed to requirements for the remainder of gestation.

Analysis of Variance↗

Influence of maternal dexamethasone administration on thermoregulation in lambs delivered by caesarean section.

We have previously shown that lambs delivered by caesarean section 1 week prematurely become hypothermic due to reduced brown adipose tissue function in conjunction with low plasma concentrations of cortisol and thyroid hormones. The present study therefore aimed to determine whether maternal dexamethasone (a synthetic corticosteroid) administration could improve thermoregulation in premature lambs to the extent that they become similar to term lambs. Lambs were either delivered by caesarean section into a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature at 140 days of gestation, 2 days after maternal dexamethasone treatment, or at 146 days for controls. During the first 30 min of life the decline in colonic temperature was greater in dexamethasone treated lambs compared with controls delivered into the same ambient temperature. All lambs then restored colonic temperature although this adaptation took longest in dexamethasone treated lambs CD but these subsequently attained highest plateau colonic temperatures. Oxygen consumption, breathing frequency and plasma free fatty acid concentrations were highest in dexamethasone treated lambs CD. There were no differences in plasma thyroid hormones between groups, but cortisol concentrations were lower in dexamethasone treated lambs irrespective of delivery temperature. Analysis of brown adipose tissue samples at 6 h of life demonstrated that dexamethasone treated lambs WD had more uncoupling protein and, in both dexamethasone treated and control lambs, uncoupling protein content was higher in lambs CD compared with those WD. An effect of ambient temperature on thermogenic activity was only observed in the dexamethasone treated group. It is concluded that maternal dexamethasone treatment can significantly improve thermoregulation after birth following premature delivery by caesarean section. As a consequence, dexamethasone treated lambs delivered 1 week prematurely do not remain hypothermic and have higher or similar colonic temperatures compared with untreated lambs born 1-2 days before term.

Adipose Tissue, Brown↗

Influence of maternal bodyweight on size, conformation and survival of newborn lambs.

Although body condition score was not significantly different between light (<55 kg, n = 6) and heavy (> or =60 kg, n = 7) ewes at mating, it declined between Day 30 and Day 90 of gestation in light but not heavy ewes, and remained lower up to term. All ewes bore twins, delivered near term (Days 144-146) by Caesarean section. One lamb was immediately placed into a warm (30 degrees C; WD) and its twin into a cool (15 degrees C; CD) ambient temperature, and tissues were sampled at 0.5 h or 6 h. All CD lambs born to light ewes exhibited hypothermia and/or respiratory failure and did not survive longer than 30 min; these symptoms were not observed in their WD twins or any lamb born to heavy ewes. Total lamb birth weight, placental weight and fetal cotyledonary weight were lower with light than with heavy ewes. Lambs born to light ewes had less perirenal adipose tissue and smaller liver, heart, kidneys, brain, adrenals and thyroid, although their heart, brain and pancreas represented a larger proportion of total bodyweight; pancreas weight was similar to that in lambs born to heavy ewes. Hence, maternal bodyweight critically influences placental weight and lamb size and survival after birth.

Animals↗

Maternal manipulation of brown adipose tissue and liver development in the ovine fetus during late gestation.

We examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126, 140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possessed more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5' deiodinase (EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine 5' deiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development.

Adaptation, Physiological↗

Influence of feeding and ambient temperature on thermoregulation in newborn lambs.

This study examined the effect of ambient temperature and feeding on brown adipose tissue (BAT) function and thermoregulation in lambs born either vaginally at term or by Caesarean section close to term. Immediately after birth lambs were placed in a warm (30 degrees C) or cool (15 degrees C) ambient temperature and measurements of colonic temperature and heat production recorded for 6 h. Lambs were fed 50 ml of colostrum when 5 h old. The amount of uncoupling protein and level of guanosine 5'diphosphate (GDP) binding in BAT was higher in vaginally delivered lambs than in lambs delivered by Caesarean section. For each delivery group, GDP binding was greater in lambs maintained at 30 degrees C than in lambs maintained at 15 degrees C. O2 consumption, CO2 production and colonic temperature only increased after feeding in lambs born by Caesarean section and maintained at 30 degrees C, a response that was accompanied by a decreased incidence of shivering. Irrespective of delivery temperature, plasma thyroid hormone concentrations and noradrenaline content of BAT were lower in lambs born by Caesarean section than in those born vaginally. Plasma cortisol concentrations were higher in lambs delivered by Caesarean section, as was adrenaline content of BAT in these lambs maintained at 30 degrees C. It is concluded that the thermoregulatory response to feeding in terms of changes in both recruitment of shivering and colonic temperature were observed only in lambs delivered by Caesarean section.

Adipose Tissue, Brown↗

Plasma prolactin concentrations after caesarean section or vaginal delivery.

The umbilical venous plasma prolactin concentrations of three groups of term infants were compared immediately after birth. Samples were taken following seven vaginal deliveries, eight emergency caesarean sections performed during labour, and 12 elective caesarean sections before labour. Mean concentrations of prolactin were significantly lower in the elective caesarean section group compared with the labour groups. This result indicates that the fetal hypothalamic-pituitary axis is stimulated during labour which could explain the increase in plasma prolactin concentrations at birth.

Biomarkers↗

Influence of route of delivery and ambient temperature on thermoregulation in newborn lambs.

We examined the effect of route of delivery on brown adipose tissue (BAT) function and thermoregulation in lambs born either vaginally at term or by cesarean section close to term. Immediately after birth, lambs were placed in a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature, and measurements of colonic temperature, plus heat production (i.e., oxygen consumption and carbon dioxide production), were recorded for 6 h. Over the first 30 min of life, colonic temperature remained constant in vaginally delivered lambs and was lower in the WD group. Following cesarean section delivery, colonic temperature declined rapidly, a response that was greater in the CD group. Cesarean section-delivered lambs had an increased reliance on shivering thermogenesis and restored colonic temperature after 2 h, and by 6 h these parameters were higher than in lambs born vaginally. Irrespective of delivery, temperature, plasma thyroid hormone concentrations and norepinephrine content of BAT were lower in lambs born by cesarean section compared with those born vaginally. Plasma cortisol concentrations and epinephrine content of BAT were greater in lambs born by cesarean section. The amount of uncoupling protein and level of guanosine 5'-diphosphate binding in BAT were higher in vaginally delivered than in cesarean section-delivered lambs, and for each group mean values were greater for CD than WD lambs. Cesarean section delivery results in altered thyroidal, adrenal, and sympathetic activity, which appears to have a marked influence on BAT function, thereby contributing to distinct differences in thermoregulation compared with lambs born vaginally.

Adipose Tissue↗