Placental insufficiency induces a sexually dimorphic response in the expression of cardiac growth and metabolic signalling molecules upon exposure to a postnatal western diet in guinea pigs

Abstract There is a strong relationship between low birth weight (LBW) and an increased risk of developing cardiovascular disease (CVD). In postnatal life, LBW offspring are becoming more commonly exposed to the additional independent CVD risk factors, such as an obesogenic diet. However, how an already detrimentally programmed LBW myocardium responds to a secondary insult, such as an obesogenic diet (western diet; WD), during postnatal life is ill defined. Herein, we aimed to determine in a pre-clinical guinea pig model of CVD, both the independent and interactive effects of LBW and a postnatal WD on the molecular pathways that regulate cardiac growth and metabolism. Uterine artery ablation was used to induce placental insufficiency (PI) in pregnant guinea pigs to generate LBW offspring. Normal birth weight (NBW) and LBW offspring were weaned onto either a Control diet or WD. At ˜145 days after birth (young adulthood), male and female offspring were humanely killed, the heart weighed and left ventricle tissue collected. The mRNA expression of signalling molecules involved in a pathological hypertrophic and fibrotic response was increased in the myocardium of LBW male, but not female offspring, fed a WD as was the mRNA expression of transcription factors involved in fatty acid oxidation. The mRNA expression of glucose transporters was downregulated by LBW and WD in male, but not female hearts. This study has highlighted a sexually dimorphic cardiac pathological hypertrophic and fibrotic response to the secondary insult of postnatal WD consumption in LBW offspring.

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THE 'EARLY ANDROGEN SYNDROME' IN THE GUINEA-PIG

Journal of Endocrinology ◽

10.1677/joe.0.0490277 ◽

1971 ◽

Vol 49 (2) ◽

pp. 277-291 ◽

Cited By ~ 23

Author(s):

K. BROWN-GRANT ◽

M. R. SHERWOOD

Keyword(s):

Guinea Pig ◽

External Genitalia ◽

Female Offspring ◽

Postnatal Life ◽

Vaginal Opening ◽

Vaginal Smears ◽

Short Period ◽

Luteal Tissue ◽

Pituitary Glands ◽

Androgenic Steroids

SUMMARY When testosterone propionate was administered to pregnant guinea-pigs over a short period (days 33–37) of gestation a high proportion of the female offspring exhibited a characteristic syndrome. The time of the first vaginal opening was delayed and its duration reduced. Subsequent periods of opening were fairly regular in occurrence but were shorter in duration than in normal animals; the 'cycle' length was usually slightly longer. Continuous vaginal opening was not observed but during the periods of opening, vaginal smears containing many cornified cells and no leucocytes were obtained. During the periods of vaginal opening no lordosis response to manual stimulation could be elicited nor did the animals mate when run with males. The increase in body weight was normal up to about 150 days of age and slightly, but not significantly, less than that of controls between 150 and 200 days of postnatal life. As adults some masculinization of the external genitalia was observed. At autopsy the weights of the uteri, ovaries, adrenal and anterior pituitary glands were much greater than those of control animals at any stage of the cycle. Histological examination showed that the ovaries contained many antral follicles but no luteal tissue. Enlargement of the glands and metaplastic changes in the epithelium were observed in the uteri. The pituitaries showed an excess of cells containing large, densely packed eosinophilic granules. This early androgen syndrome is compared with that produced by hypothalamic lesions in the guinea-pig and with the changes produced in other species by the administration of androgenic steroids during prenatal or early postnatal life.

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Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00676.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. R1810-R1818 ◽

Cited By ~ 49

Author(s):

Claire J. Stocker ◽

Ed Wargent ◽

Jacqueline O'Dowd ◽

Claire Cornick ◽

John R. Speakman ◽

...

Keyword(s):

Weight Gain ◽

Energy Balance ◽

Glucose Tolerance ◽

Female Offspring ◽

Male Offspring ◽

Male Rats ◽

Fat Pad ◽

Plasma Insulin Concentration ◽

Obesogenic Diet ◽

Tolerance Curve

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg·kg−1·day−1) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.

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Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00606.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. E920-E929 ◽

Cited By ~ 23

Author(s):

Esben S. Buhl ◽

Thomas Korgaard Jensen ◽

Niels Jessen ◽

Betina Elfving ◽

Christian S. Buhl ◽

...

Keyword(s):

Insulin Resistance ◽

Birth Weight ◽

Insulin Sensitivity ◽

Low Birth Weight ◽

Mrna Expression ◽

Hpa Axis ◽

Whole Body ◽

Oral Glucose ◽

Red Muscle ◽

Hpa Axis Activity

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4–5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phospho enolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser473phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW ( P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion ( P < 0.05 vs. Cx), whole body insulin resistance ( P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression ( P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser473phosphorylation. The ESC treatment normalized corticosterone secretion ( P < 0.05 vs. LBW), whole body insulin sensitivity ( P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression ( P < 0.05), and red muscle PKB Ser473phosphorylation ( P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

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Catch-up Growth in Intrauterine Growth-restricted Piglets Associated with the Return of Pancreatic and Intestinal Functions via Porcine Glucagon-like peptide-2 Microspheres

10.21203/rs.2.21967/v1 ◽

2020 ◽

Author(s):

Ke-ke Qi ◽

Jie Wu ◽

Wen-Jun Zhou ◽

Bo Deng ◽

Xiao-ming Men ◽

...

Keyword(s):

Body Weight ◽

Birth Weight ◽

Mrna Expression ◽

Glucose Transporter ◽

Serum Insulin ◽

The Body ◽

Peptide Transporter ◽

Control Group ◽

Intrauterine Growth ◽

Glucagon Like Peptide

Abstract Background Intrauterine growth restriction (IUGR) results in abnormal morphology and gastrointestinal function. As a gastrointestinal growth factor, the manner by which the porcine glucagon-like peptide-2 (pGLP-2) microsphere administration catches up with the growth of IUGR piglets was investigated. Methods Fourteen newborn IUGR piglets were assigned into the IUGR and pGLP-2 microsphere groups. The piglets in the pGLP-2 microsphere group were intraperitoneally administered with 100 mg of pGLP-2 microspheres on day 1 of birth. Results From days 15 to 26 of trial, the body weight of the IUGR piglets treated with pGLP-2 microspheres was significantly higher than that in the control group. Importantly, the weaning weight in the pGLP-2 group catches up with the body weight of normal birth weight piglets. IUGR piglets treated with pGLP-2 microspheres significantly showed increased pancreas weight, serum insulin content, and activities of digestive enzymes (lipase, trypsin, chymotrypsin, and amylase). Injection of pGLP-2 microspheres returned the intestinal absorptive capacity by significantly increasing the mRNA expression of sodium-glucose cotransporter 1 in the jejunum, glucose transporter type 2 in the duodenum and jejunum, H + -coupled transporter, and peptide transporter 1 in the jejunum and ileum. It also returned the redox balance by increasing the catalase mRNA expression and decreasing the heat shock protein 70 mRNA expression. In addition, this improvement was associated with the significant increase in gut diameter, length, and weight induced by pGLP-2. Conclusions Injection of pGLP-2 microspheres was a suitable therapeutic strategy for compensatory growth in low birth weight IUGR piglet.

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Intravenous administration of arginine to twin-bearing ewes enhances birth weight and peri-renal fat stores of female offspring in sheep

Energy and protein metabolism and nutrition in sustainable animal production ◽

10.3920/978-90-8686-781-3_146 ◽

2013 ◽

pp. 405-406

Author(s):

S. McCoard ◽

F. Sales ◽

N. Wards ◽

Q. Sciascia ◽

M. Oliver ◽

...

Keyword(s):

Birth Weight ◽

Intravenous Administration ◽

Female Offspring ◽

Fat Stores

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Leptin levels at birth and in early postnatal life in small- and appropriate-for-gestational-age infants

Medicina ◽

10.3390/medicina43100100 ◽

2007 ◽

Vol 43 (10) ◽

pp. 784 ◽

Cited By ~ 22

Author(s):

Margarita Valūnienė ◽

Rasa Verkauskienė ◽

Margaret Boguszewski ◽

Jovanna Dahlgren ◽

Danutė Lašienė ◽

...

Keyword(s):

Birth Weight ◽

Gestational Age ◽

Small For Gestational Age ◽

Venous Blood ◽

Postnatal Life ◽

Abrupt Decrease ◽

Blood Samples ◽

Appropriate For Gestational Age ◽

Early Postnatal Life ◽

The Impact

The aim of this study was to evaluate leptin concentration at birth and in early postnatal life in small- and appropriate-for-gestational-age infants and to assess its relationship with infants’ anthropometry at birth and some characteristics of maternal pregnancy. Materials and methods. A total of 367 infants born after 32–42 weeks of gestation were enrolled in the study. Umbilical cord blood samples were collected from 80 small- and 287 appropriate- for-gestational-age newborns. Altogether, 166 venous blood samples were taken from these neonates on days 2–6 of life. Results. Cord leptin levels were significantly lower in small- compared to appropriate-forgestational- age infants. We observed a positive correlation between cord leptin and birth weight, all neonatal anthropometric parameters, placental weight, and some maternal nutritional factors. In multivariate analysis, cord leptin concentration explained up to 15% of the variation in sum of newborn’s skinfold thickness but only 5% of the variation in birth weight. Postnatally, leptin concentration decreased markedly to the similar low levels in both infant groups and remained so during the first postnatal week. Conclusions. Significantly lower cord leptin concentration in small-for-gestational-age neonates reflects a lower fat mass content compared to appropriate-for-gestational-age infants. However, an abrupt decrease in leptin levels shortly after birth in both groups suggests that placenta could be an important source of leptin in fetal circulation. The impact of low leptin levels at birth in small-for-gestational-age infants on their postnatal appetite and weight gain remains to be elucidated in future studies.

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Nutritional challenges during development induce sex-specific changes in glucose homeostasis in the adult sheep

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00253.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. E32-E39 ◽

Cited By ~ 26

Author(s):

Kirsten R. Poore ◽

Jane K. Cleal ◽

James P. Newman ◽

Julian P. Boullin ◽

David E. Noakes ◽

...

Keyword(s):

Body Composition ◽

Insulin Sensitivity ◽

Glucose Homeostasis ◽

Area Under The Curve ◽

Postnatal Growth ◽

Female Offspring ◽

Postnatal Life ◽

Intravenous Glucose ◽

Ad Libitum ◽

Early Postnatal Life

The early-life environment has implications for risk of adult-onset diseases, such as glucose intolerance, insulin insensitivity, and obesity, effects that may occur with or without reduced birth weight. We determined the consequences of nutrient restriction in early gestation and early postnatal life and their interactions on postnatal growth, body composition, and glucose handling. Ewes received 100% (C, n = 39) or 50% nutritional requirements (U, n = 41) from 1 to 31 days gestation and 100% thereafter. Male and female offspring (singleton/twin) from C and U ewes were then fed either ad libitum (CC n = 22, UC n = 19) or to reduce body weight to 85% of target from 12 to 25 wk of age (CU n = 17, UU n = 22) and ad libitum thereafter. At 1.5 and 2.5 yr, glucose handling was determined by area under the curve (AUC) for glucose and insulin concentrations following intravenous glucose (0.5 g/kg body wt). Insulin sensitivity was determined at 2.5 yr following intravenous insulin (0.5 IU/kg). In females, postnatal undernutrition reduced ( P < 0.05) glucose AUC at both ages, regardless of prenatal nutrition. Postnatal undernutrition did not affect insulin secretion in females but enhanced insulin-induced glucose disappearance in singletons. Poor early postnatal growth was associated with increased fat in females. In males, glucose tolerance was unaffected by undernutrition despite changes in insulin AUC dependent on age, treatment, and single/twin birth. Nutrition in early postnatal life has long-lasting, sex-specific effects on glucose handling in sheep, likely due, in females, to enhanced insulin sensitivity. Improved glucose utilization may aid weight recovery but have negative implications for glucose homeostasis and body composition over the longer term.

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Blocking cardiac growth in hypertrophic cardiomyopathy induces cardiac dysfunction and decreased survival only in males

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00615.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. H838-H845 ◽

Cited By ~ 20

Author(s):

Stephen W. Luckey ◽

Jason Mansoori ◽

Kelly Fair ◽

Christopher L. Antos ◽

Eric N. Olson ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Mouse Model ◽

Glycogen Synthase ◽

Contractile Function ◽

Premature Death ◽

Contractile Dysfunction ◽

Sexually Dimorphic ◽

Cardiac Growth ◽

Hypertrophic Growth ◽

Gsk 3Β

Mutations in myosin heavy chain (MyHC) can cause hypertrophic cardiomyopathy (HCM) that is characterized by hypertrophy, histopathology, contractile dysfunction, and sudden death. The signaling pathways involved in the pathology of HCM have not been elucidated, and an unresolved question is whether blocking hypertrophic growth in HCM may be maladaptive or beneficial. To address these questions, a mouse model of HCM was crossed with an antihypertrophic mouse model of constitutive activated glycogen synthase kinase-3β (caGSK-3β). Active GSK-3β blocked cardiac hypertrophy in both male and female HCM mice. However, doubly transgenic males (HCM/GSK-3β) demonstrated depressed contractile function, reduced sarcoplasmic (endo) reticulum Ca2+-ATPase (SERCA) expression, elevated atrial natriuretic factor (ANF) expression, and premature death. In contrast, female HCM/GSK-3β double transgenic mice exhibited similar cardiac histology, function, and survival to their female HCM littermates. Remarkably, dietary modification from a soy-based diet to a casein-based diet significantly improved survival in HCM/GSK-3β males. These findings indicate that activation of GSK-3β is sufficient to limit cardiac growth in this HCM model and the consequence of caGSK-3β was sexually dimorphic. Furthermore, these results show that blocking hypertrophy by active GSK-3β in this HCM model is not therapeutic.

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Mature and immature platelets during the first week after birth and incidence of patent ductus arteriosus

Cardiology in the Young ◽

10.1017/s1047951120000943 ◽

2020 ◽

Vol 30 (6) ◽

pp. 769-773 ◽

Cited By ~ 1

Author(s):

Hannes Sallmon ◽

Boris Metze ◽

Petra Koehne ◽

Bernd Opgen-Rhein ◽

Katja Weiss ◽

...

Keyword(s):

Platelet Count ◽

Birth Weight ◽

Patent Ductus Arteriosus ◽

Very Low Birth Weight ◽

Ductus Arteriosus ◽

Postnatal Life ◽

Platelet Counts ◽

Immature Platelet Fraction ◽

Immature Platelets ◽

Patent Ductus

AbstractBackground:Thrombocytopenia is a risk factor for patent ductus arteriosus. Immature and mature platelets exhibit distinct haemostatic properties; however, whether platelet maturity plays a role in postnatal, ductus arteriosus closure is unknown.Methods:In this observational study, counts of immature and mature platelets (=total platelet count − immature platelet count) were assessed on days 1, 3, and 7 of life in very low birth weight infants (<1500 g birth weight). We performed echocardiographic screening for haemodynamically significant patent ductus arteriosus on day 7.Results:Counts of mature platelets did not differ on day 1 in infants with (n = 24) and without (n = 45) haemodynamically significant patent ductus arteriosus, while infants with significant patent ductus arteriosus exhibited lower counts of mature platelet on postnatal days 3 and 7. Relative counts of immature platelets (fraction, in %) were higher in infants with patent ductus arteriosus on day 7 but not on days 1 and 3. Receiver operating characteristic curve analysis unraveled associations between both lower mature platelet counts and higher immature platelet fraction (percentage) values on days 3 and 7, with haemodynamically significant ductus arteriosus. Logistic regression analysis revealed that mature platelet counts, but not immature platelet fraction values, were independent predictors of haemodynamically significant patent ductus arteriosus.Conclusion:During the first week of postnatal life, lower counts of mature platelets and higher immature platelet fraction values are associated with haemodynamically significant patent ductus arteriosus. Lower counts of mature platelet were found to be independent predictors of haemodynamically significant patent ductus arteriosus.

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