010. PERICONCEPTIONAL UNDERNUTRITION: LIFE-LONG EFFECTS FOR THE OFFSPRING

2010 ◽  
Vol 22 (9) ◽  
pp. 6
Author(s):  
F. H. Bloomfield ◽  
M. H. Oliver ◽  
A. L. Jaquiery ◽  
C. Hernandez ◽  
J. R. G. Challis ◽  
...  
Keyword(s):  
Maternal Nutrition ◽  
Late Gestation ◽  
Critical Window ◽  
Maternal Undernutrition ◽  
Maternal Nutritional Status ◽  
Child Bearing ◽  
Offspring Sex ◽  
Periconceptional Period ◽  
Altered Response ◽  
Poor Nutrition

Poor nutrition in women of child-bearing age is common, even in Western countries. It has been estimated that approximately 30% of women of child-bearing age in affluent cities such as Sydney and Southampton are either actively dieting or have a nutritional intake that does not meet daily recommended requirements for all nutrients. We have investigated the effect of reduced maternal nutrition before and around the time of conception on fetal growth and development, and have followed offspring through to adulthood. In this paradigm, ewes were fed to lose 10–15% of their body weight and then to gain weight according to conceptus mass. Control ewes were well fed throughout. Different timing and duration of undernutrition in the periconceptional period were utilised to investigate the most critical window for fetal development. Periconceptional undernutrition resulted in accelerated development of the fetal hypothalamic-pituitary-adrenal (HPA) and glucose-insulin axes in late gestation, and preterm birth. Offspring of periconceptionally undernourished ewes demonstrated altered laterality and an altered response to isolation stress; HPA axis function was also suppressed. As offspring aged, glucose tolerance decreased and became significantly impaired by young adulthood compared with control offspring. The effects of maternal undernutrition on offspring were modified by offspring sex and also by being one of a twin pair. Interestingly, our data also demonstrate that conception as a twin, regardless of maternal nutritional status, also affects all these outcomes but in a different way to maternal undernutrition. Preliminary data suggest that epigenetic changes in feeding centres of the hypothalamus may play a role in the mechanism behind some of these effects. These studies suggest that even moderate maternal undernutrition in very early pregnancy has life-long effects. Should this also be true in humans, then health care messages for women may need to be targeted prior to pregnancy.

EFFECTS OF MATERNAL NUTRITION ON THE HUMAN FETUS

PEDIATRICS ◽  
1973 ◽  
Vol 52 (4) ◽  
pp. 494-503
Author(s):  
Richard L. Naeye ◽  
William Blanc ◽  
Cheryl Paul
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Maternal Nutrition ◽  
Cellular Growth ◽  
Late Gestation ◽  
Third Trimester ◽  
Organ Growth ◽  
Maternal Undernutrition ◽  
The Third ◽  
Body Organ

In a study of 467 gestations maternal stature had little correlation with fetal growth but mother's pregravid body weight as well as weight gain and low-calorie diets during pregnancy did have such a correlation. Maternal undernutrition before the third trimester had little or no influence on fetal body, organ, and cellular growth while such effects were pronounced in late gestation. Fetal body and organ growth improved with successive pregnancies except in the most poorly nourished mothers, whose successive neonates became more growth retarded.

Maternal undernutrition during the first week after conception results in decreased expression of glucocorticoid receptor mRNA in the absence of GR exon 17 hypermethylation in the fetal pituitary in late gestation

2013 ◽  
Vol 4 (5) ◽  
pp. 391-401 ◽  
Author(s):  
S. Zhang ◽  
O. Williams-Wyss ◽  
S. M. MacLaughlin ◽  
S. K. Walker ◽  
D. O. Kleemann ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Early Embryo ◽  
Late Gestation ◽  
Control Group ◽  
Fetal Sheep ◽  
Maternal Undernutrition ◽  
Stress Responsiveness ◽  
Periconceptional Period

Exposure to maternal undernutrition during the periconceptional period results in an earlier prepartum activation of the fetal hypothalamo–pituitary–adrenal (HPA) axis and altered stress responsiveness in the offspring. It is not known whether such changes are a consequence of exposure of the oocyte and/or the early embryo to maternal undernutrition in the periconceptional period. We have compared the effects of ‘periconceptional’ undernutrition (PCUN: maternal undernutrition imposed from at least 45 days before until 6 days after conception), and ‘early preimplantation’ undernutrition (PIUN: maternal undernutrition imposed for only 6 days after conception) on the expression of genes in the fetal anterior pituitary that regulate adrenal growth and steroidogenesis, proopiomelanorcortin (POMC), prohormone convertase 1 (PC1), 11β-hydroxysteroid dehydrogenase type 1 and 2 (11βHSD1 and 2) and the glucocorticoid receptor (GR) in fetal sheep at 136–138 days of gestation. Pituitary GR mRNA expression was significantly lower in the PCUN and PIUN groups in both singletons and twins compared with controls, although this suppression of GR expression was not associated with hypermethylation of the exon 17 region of the GR gene. In twin fetuses, the pituitary 11βHSD1 mRNA expression was significantly higher in the PIUN group compared with the PCUN but not the control group. Thus, exposure of the single or twin embryo to maternal undernutrition for only 1 week after conception is sufficient to cause a suppression of the pituitary GR expression in late gestation. These changes may contribute to the increased stress responsiveness of the HPA axis in the offspring after exposure to poor nutrition during the periconceptional period.

scholarly journals Embryo number and periconceptional undernutrition in the sheep have differential effects on adrenal epigenotype, growth, and development

2014 ◽  
Vol 307 (2) ◽  
pp. E141-E150 ◽  
Author(s):  
Olivia Williams-Wyss ◽  
Song Zhang ◽  
Severence M. MacLaughlin ◽  
David Kleemann ◽  
Simon K. Walker ◽  
...  
Keyword(s):  
Maternal Nutrition ◽  
Differentially Methylated Region ◽  
Epigenetic Changes ◽  
Plasma Acth ◽  
Differential Effects ◽  
Fetal Plasma ◽  
Maternal Undernutrition ◽  
Periconceptional Period ◽  
Embryo Number ◽  
Pituitary Adrenal Axis

Exposure to poor maternal nutrition around the time of conception results in an early prepartum activation of the fetal pituitary-adrenal axis and in increased adrenal growth and stress response after birth associated with epigenetic changes in a differentially methylated region (DMR) of adrenal IGF2/H19. We have determined the effects of maternal undernutrition during the periconceptional period (PCUN: 70% of control intake from 60 days before until 6 days after conception) and early preimplantation period (PIUN: 70% of control intake for 6 days after conception) on fetal plasma ACTH and cortisol concentrations and fetal adrenal ACTHR, StAR, 3βHSD, CYP11B, CYP17, TGFβ1, IGF1, IGF1R, IGF2, and IGF2R mRNA expression and the methylation level of sites within the DMRs of IGF2/H19 and IGF2R in the adrenal of twin and singleton fetuses at 136–138 days gestation. Being a twin resulted in a delayed prepartum increase in fetal ACTH and in a lower cortisol response to CRH in the control but not PCUN and PIUN groups. PCUN, but not PIUN, resulted in an increase in adrenal weight and CYP17 expression in singletons, a decrease in adrenal IGF2 expression in singletons, and an increase in adrenal IGF2R expression in both twins and singletons. IGF2/H19 and IGF2R DMR methylation levels and ACTHR expression were lower in the twin adrenal. Thus, exposure of the oocyte and embryo to maternal undernutrition or to the environment of a twin pregnancy have differential effects on epigenetic and other factors that regulate fetal adrenal growth and IGF2 and IGF2R expression.

scholarly journals The effect of maternal undernutrition on ovine fetal growth

2002 ◽  
Vol 173 (1) ◽  
pp. 131-141 ◽  
Author(s):  
JC Osgerby ◽  
DC Wathes ◽  
D Howard ◽  
TS Gadd
Keyword(s):  
Fetal Growth ◽  
Bone Growth ◽  
Maternal Nutrition ◽  
Fetal Brain ◽  
Late Gestation ◽  
Adult Health ◽  
Semitendinosus Muscle ◽  
Fetal Plasma ◽  
Maternal Undernutrition ◽  
Igf I

Modifications in maternal nutrition during pregnancy can significantly disrupt fetal growth and subsequent post-natal health and survival. This study investigated the effects of undernutrition on fetal growth and the potential mechanisms involved. Tissue from pregnant ewes (n=27) was investigated on days 45, 90 and 135 of gestation (term = approximately 150 days). The thoracic girth (P<0.05) was greater in fetuses from nutrient restricted ewes on day 45 and there was also a trend towards an increased gut weight (P<0.08). By day 90, the fetal brain and thymus weight were lighter in underfed than in well-fed animals whilst the weight of the fetal ovaries was heavier (P<0.05). On day 135 the fetal heart, pancreas, thymus, gut and kidney weights were lighter in undernourished ewes (P<0.05). When expressed as a percentage of fetal body weight, significance was retained in the heart, pancreas and thymus (P<0.05). Bone growth was also affected. At day 90 the fetal femur and metatarsal were longer in underfed mothers (P<0.05). In contrast, the fetal humerus and scapula were shorter in underfed than in well-fed animals on day 135 (P<0.05) when the weight of the semitendinosus muscle (P<0.05) was also reduced. The fall in fetal glucose (P<0.1), insulin (P<0.01) and IGF-I (P<0.01) levels in underfed ewes on day 135 may have compromised fetal growth. Fetal plasma IGF binding protein-2 also increased between days 90 and 135 in underfed ewes (P<0.03), whilst levels were unaltered in well-fed animals. Although maternal and fetal plasma IGF-I levels increased with gestation (P<0.01) and the placentome morphology altered in all ewes (P<0.05), the fall in placental mass (P<0.05), amniotic and allantoic glucose concentrations (P<0.05) and maternal plasma glucose and insulin levels (P<0.05) in underfed ewes in late gestation may have compromised fetal substrate delivery. These perturbations in fetal development may have significant implications on adult health and carcass conformation, raising important health and economic issues in medical and agricultural sectors.

scholarly journals Understanding the effects of maternal undernutrition in early gestation on placental development in late gestation

2018 ◽  
Author(s):  
◽  
Gerialisa Allison Marcella Van Gronigen Case
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Maternal Nutrition ◽  
Financial Burden ◽  
Late Gestation ◽  
Placental Development ◽  
Early Gestation ◽  
Maternal Undernutrition ◽  
Increased Risk ◽  
The U.S

Chronic diseases such as cardiovascular disease and diabetes are on the rise among the U.S. population. Heart Disease is the leading cause of death in the US and is responsible 610,000 deaths per year. A suite of risk factors for cardiovascular disease and diabetes â€" obesity, elevated blood sugar,hypertension, excess cholesterol, and elevated triglycerides, referred to asMetabolic Syndrome, contributes to an increased risk of mortality. These too areincreasingly prevalent. For example, according to the CDC, in 2011 more than 35% of the U.S. population was obese, with a financial burden of US $147 billion annually. Though improper diet, lack of exercise and socioeconomic status areassociated with these adult diseases, inadequate maternal nutrition just prior toor during pregnancy is also a risk factor. The goal of my research is to identifythe critical time point by which maternal under-nutrition (MUN) during earlygestation permanently alters placental development, the mechanism by whichthis occurs, and whether leptin acts as a mediator.The relationship between the maternal environment and long-term healthof offspring is referred to as the developmental origins of health and disease (DOHaD), or sometimes fetal programming. MUN during pregnancy may affectdeveloping organs to alter the phenotypic outcome of the offspring to promoteadult disease. The timing of the insult is also critical. During the periconceptionalperiod and early gestation, there are major developmental processes such asembryonic organogenesis, and placenta formation. There are also two rounds of DNA methylation reprogramming that occur. I investigated the effects of maternalunder-nutrition from three weeks prior to gestation to d 11.5 (mid gestation inmice). I found that maternal periconceptional food restriction until mid- gestationaffected formation of blood spaces within the labyrinthine placenta near term, ascompared to those from control-fed dams. There was also a three-fold decreasein mRNA encoding SNAT4, an amino acid transporter, in restricted placentae.These changes in placentae from dams fed a nutrient restricted diet suggestsome compensation to ensure adequate nutrients are available to the fetus forproper development.I also examined the effects MUN undernutrition during the first half ofgestation had on placental DNA methylation at late gestation and whether leptinwould act as a mediator of these effects. It is not entirely understood howinformation about maternal nutrition is sensed by the placenta. Leptin, is ahormone that is secreted by fat tissue and plays a role in energy homeostasis,metabolism and reproduction. Therefore, it could be one potential mechanism bywhich maternal nutrition can influence placental function and in turn, fetaldevelopment. I found placentae from dams who experienced MUN and leptinsupplementation had a greater number of differentially methylated regionscompared to placentae from dams fed an adequate fed diet than did placentae ofdams fed MUN only. Regions that were differentially methylated by maternal dietand/or leptin supplementation were located near genes in pathways involved inmolecular transport and carbohydrate metabolism as well as postnatal growth,weight and body size, formation of new blood vessels during embryogenesis. These pathways suggest a link between maternal food deprivation andoffspring's' growth, metabolism and formation of the cardiovascular system.

154 UNDERNUTRITION DURING THE PERICONCEPTIONAL PERIOD IN EWES AFFECTS THE BLOOD PRESSURE AND WEIGHT OF THEIR NEONATAL LAMBS

2007 ◽  
Vol 19 (1) ◽  
pp. 194
Author(s):  
N. A. Smith ◽  
P. Lonergan ◽  
P. Duffy ◽  
T. F. Crosby ◽  
P. Quinn ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Birth Weight ◽  
Maternal Nutrition ◽  
Experimental Studies ◽  
Control Treatment ◽  
Maternal Undernutrition ◽  
Increased Risk ◽  
Periconceptional Period ◽  
Offspring Health ◽  
The Impact

Evidence from epidemiological and experimental studies has shown that maternal undernutrition during pregnancy can alter fetal growth and development and is associated with increased risk of hypertension and cardiovascular disease in the offspring. However, there is a paucity of data examining the effect of undernutrition during the periconceptual period on offspring health. Therefore, we investigated the impact of ewe undernutrition during the periconceptional period on lamb birth weight and blood pressure. Crossbred ewes (n = 166) were individually penned and randomly allocated to 1 of 2 treatments and fed either 0.7 (restricted) or 1.1 (control) maintenance energy requirements from 28 days prior until 7 days post-mating. After Day 7, ewes in both treatments were managed similarly until parturition. Following parturition, lamb gender, birth weight, and blood pressure were recorded. Lamb weight and blood pressure were subsequently measured at 4 and 10 weeks of age. Restricted ewes lost 2.6 � 0.2 kg over the treatment period compared with control ewes which gained 1.7 � 0.58 kg (P &lt; 0.01). There was no treatment effect on lamb birth weight in either singleton or twin gestations. However, at 4 and 10 weeks of age singleton lambs born to nutritionally restricted ewes were heavier than those born to control ewes (males, n = 17: 19.4 � 0.1 vs. 16.4 � 0.1 kg; females, n = 16: 34.9 � 1.0 vs. 30.9 � 1.6 kg, P &lt; 0.05). Blood pressure, measured within the first 24 h of life, was higher (P &lt; 0.05) in singleton lambs born to nutritionally restricted mothers compared to controls (males: systolic 126 � 11 vs. 94 � 5; diastolic 99 � 12 vs. 58 � 5; mean 112 � 11 vs. 77 � 5 mmHg; P &lt; 0.05; females: systolic 126 � 11 vs. 94 � 5; diastolic 99 � 12 vs. 58 � 5; mean 112 � 11 vs. 77 � 5 mmHg; P &lt; 0.05). This difference was no longer apparent at 4 or 10 weeks of age. Mean blood pressures of twin lambs at birth and 4 weeks of age were numerically greater in the restricted than in the control treatment but were significantly different only among male twin groups at 4 weeks of age (diastolic 77 � 4 vs. 94 � 4; mean 96 � 4 vs. 110 � 3 mmHg; P &lt; 0.01). Maternal undernutrition during the periconceptional period was associated with increased offspring weight at 4 and 10 weeks of age in singletons, as well as alterations in offspring cardiovascular function in both singletons and twins. These findings suggest that maternal nutrition at the time of conception influences offspring health. Exact mechanisms remain to be elucidated but may involve genetic modification. This research was funded by IRCSET and University College Dublin.

Effects of maternal periconceptional undernutrition in sheep on offspring glucose–insulin axis function into adulthood

2020 ◽  
pp. 1-7
Author(s):  
Mark H. Oliver ◽  
Frank H. Bloomfield ◽  
Amita Bansal ◽  
Hui Hui Phua ◽  
Eric B. Thorstensen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Protein Expression ◽  
Insulin Signalling ◽  
Area Under The Curve ◽  
Late Gestation ◽  
Maternal Undernutrition ◽  
Kinase C ◽  
First Phase Insulin Secretion ◽  
Protein Kinase C Zeta

Abstract Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.

Nutritional programming and the reproductive function of the offspring

2014 ◽  
Vol 54 (9) ◽  
pp. 1166 ◽  
Author(s):  
P. Chavatte-Palmer ◽  
C. Dupont ◽  
N. Debus ◽  
S. Camous
Keyword(s):  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Maternal Nutrition ◽  
Reproductive Function ◽  
Fetal Life ◽  
Ample Evidence ◽  
Primordial Follicles ◽  
Intrauterine Growth ◽  
Maternal Undernutrition ◽  
Males And Females

There is ample evidence on the importance of maternal nutrition during pregnancy on fetal and offspring development. In ruminant females, the pool of oocytes is complete and definitive before birth, based on the resting reserve of primordial follicles established during fetal life, which represent the lifespan supply for the female’s fertilisable oocytes, whereas in males, although the production of spermatozoa is a continuous process throughout post-pubertal life. Sertoli cells, which play a central role in the development of a functional testis, proliferate during pre- and post-natal life, coordinating testicular development. Both male and female fertility may, therefore, be affected by the maternal environment, but studies on the effects of developmental nutritional conditions on reproductive function and fertility, both in males and females, are relatively scarce. In humans, intrauterine growth retardation has been associated with abnormal ovarian development, characterised by a decreased volume of primordial follicles in the ovarian cortical tissue in girls, and a higher incidence of cryptorchidism in boys, with subsequent low sperm counts in adulthood. Age at puberty and gonadotropin and inhibin B plasma concentrations are also affected. Animal studies suggest both in males and females that maternal undernutrition during pregnancy may affect pituitary response to GnRH and gonadal development and function, depending on the timing and magnitude of the undernutrition. Excess nutrition, which is often associated with intrauterine growth retardation in domestic species, induces effects on the onset of puberty and both testicular and ovarian function, maybe through the observed reduction in fetal growth. This review addresses the influence of maternal nutrition on offspring reproductive function using examples in humans and animals, with particular focus on ruminants.

scholarly journals Fetal endocrinology and development--manipulation and adaptation to long-term nutritional and environmental challenges

Reproduction ◽  
2001 ◽  
pp. 853-862 ◽  
Author(s):  
ME Symonds ◽  
H Budge ◽  
T Stephenson ◽  
IC McMillen
Keyword(s):  
Adipose Tissue ◽  
Maternal Nutrition ◽  
Uncoupling Protein ◽  
Prolactin Receptor ◽  
Endocrine System ◽  
Adult Obesity ◽  
Maternal Undernutrition ◽  
Increased Risk ◽  
Long Form

This article reviews the fetal endocrine system in sheep, a species that has a long gestation and primarily produces a singleton fetus. Attention is focused on information that is applicable to humans. The endocrinology of metabolic homeostasis in sheep fetuses is well adapted to respond to a range of metabolic challenges, including placental restriction and maternal undernutrition. A small placenta results in hypoxaemia, hypoglycaemia, reduced abundance of anabolic hormones, and fetal growth restriction. Fetuses with restricted growth are characterized by tissue-specific reductions in hormone receptor mRNA, for example mRNA for the long form of prolactin receptor is reduced in adipose tissue. In contrast, the adipose tissue of fetuses with accelerated growth, stimulated by increasing maternal nutrition in the second half of gestation, has more protein for the long form of the prolactin receptor and more uncoupling protein 1, by which large amounts of heat are generated at birth. Maternal undernutrition in early gestation, coinciding with the period of rapid placental growth, initially restricts placental growth, but when mothers are fed to requirements, a longer fetus results with a disproportionately large placenta. This nutritional manipulation replicates, in part, epidemiological findings from the Dutch famine of 1944-1945, for which the offspring are at increased risk of adult obesity.

scholarly journals Late gestation undernutrition can predispose for visceral adiposity by altering fat distribution patterns and increasing the preference for a high-fat diet in early postnatal life

2012 ◽  
Vol 109 (11) ◽  
pp. 2098-2110 ◽  
Author(s):  
M. O. Nielsen ◽  
A. H. Kongsted ◽  
M. P. Thygesen ◽  
A. B. Strathe ◽  
S. Caddy ◽  
...  
Keyword(s):  
Subcutaneous Fat ◽  
Normal Diet ◽  
Visceral Adiposity ◽  
Late Gestation ◽  
The Other ◽  
Postnatal Life ◽  
High Fat ◽  
Sheep Model ◽  
Maternal Undernutrition ◽  
The Metabolic Syndrome

We have developed a sheep model to facilitate studies of the fetal programming effects of mismatched perinatal and postnatal nutrition. During the last trimester of gestation, twenty-one twin-bearing ewes were fed a normal diet fulfilling norms for energy and protein (NORM) or 50 % of a normal diet (LOW). From day 3 postpartum to 6 months (around puberty) of age, one twin lamb was fed a conventional (CONV) diet and the other a high-carbohydrate–high-fat (HCHF) diet, resulting in four groups of offspring: NORM-CONV; NORM-HCHF; LOW-CONV; LOW-HCHF. At 6 months of age, half of the lambs (all males and three females) were slaughtered for further examination and the other half (females only) were transferred to a moderate sheep diet until slaughtered at 24 months of age (adulthood). Maternal undernutrition during late gestation reduced the birth weight of LOW offspring (P< 0·05), and its long-term effects were increased adrenal size in male lambs and adult females (P< 0·05), increased neonatal appetite for fat-(P= 0·004) rather than carbohydrate-rich feeds (P< 0·001) and reduced deposition of subcutaneous fat in both sexes (P< 0·05). Furthermore, LOW-HCHF female lambs had markedly higher visceral:subcutaneous fat ratios compared with the other groups (P< 0·001). Postnatal overfeeding (HCHF) resulted in obesity (>30 % fat in soft tissue) and widespread ectopic lipid deposition. In conclusion, our sheep model revealed strong pre- and postnatal impacts on growth, food preferences and fat deposition patterns. The present findings support a role for subcutaneous adipose tissue in the development of visceral adiposity, which in humans is known to precede the development of the metabolic syndrome in human adults.

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