Effects of perinatal maternal food restriction on pituitary-gonadal axis and plasma leptin level in rat pup at birth and weaning and on timing of puberty.
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The effects of maternal 50% food restriction (FR) during the last week of gestation and/or lactation on pituitary-gonadal axis (at birth and weaning), on circulating levels of leptin (at weaning), and on the onset of puberty have been determined in rats at birth and at weaning. Maternal FR during pregnancy has no effect at term on the litter size, on the basal level of testosterone in male pups, and on the drastic surge of circulating testosterone that occurs 2 h after birth. At weaning, similar retardation of body growth is observed in male and female pups from mothers exposed to FR. This undernutrition induces the most drastic effects when it is performed during both gestation and lactation or during lactation alone. Drastic retardation of testicle growth with reduction of cross-sectional area and intratubular lumen of the seminiferous tubules is observed in male pups from mothers exposed to undernutrition during both gestation and lactation or during lactation alone. Maternal FR during the perinatal period reduces circulating levels of FSH in male pups without affecting LH and testosterone concentrations. Maternal FR does not affect circulating levels of LH, estradiol, and progesterone in female pups. Female pups from mothers exposed to FR during both gestation and lactation show a significant increase of plasma FSH as well as a drastic retardation of ovarian growth. The follicular population was also altered. The number of antral follicles of small size (vesicular follicles) was increased, although the number of antral follicles of large size (graafian follicles) was reduced. Maternal FR occurring during both late gestation and lactation (male and female pups), during lactation alone (male and female pups), or during late gestation (female pups) induces a drastic reduction of plasma leptin and fat mass in pups at weaning. The onset of puberty is delayed in pups of both sexes from mothers exposed to FR during lactation and during both gestation and lactation. In conclusion, these data demonstrate that a perinatal growth retardation induced by maternal FR has long-term consequences on both size and histology of the genitals, on plasma gonadotropins and leptin levels, on fat stores at weaning, and on the onset of puberty. (+info)
Regulation of supply and demand for maternal nutrients in mammals by imprinted genes.
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The placenta has evolved in eutherian mammals primarily to provide nutrients for the developing fetus. The genetic control of the regulation of supply and demand for maternal nutrients is not understood. In this review we argue that imprinted genes have central roles in controlling both the fetal demand for, and the placental supply of, maternal nutrients. Recent studies on Igf2 (insulin-like growth factor 2) knockout mouse models provide experimental support for this hypothesis. These show effects on placental transport capacity consistent with a role of IGF-II in modulating both the placental supply and fetal demand for nutrients. Imprinting of genes with such functions may have coevolved with the placenta and new evidence suggests that transporter proteins, as well as the regulators themselves, may also be imprinted. These data and hypotheses are important, as deregulation of supply and demand affects fetal growth and has long term consequences for health in mammals both in the neonatal period and, as a result of fetal programming, in adulthood. (+info)
Lifetime consequences of abnormal fetal pancreatic development.
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There is ample evidence that an adverse intrauterine environment has harmful consequences for health in later life. Maternal diabetes and experimentally induced hyperglycaemia result in asymmetric overgrowth, which is associated with an increased insulin secretion and hyperplasia of the insulin-producing B-cells in the fetuses. In adult life, a reduced insulin secretion is found. In contrast, intrauterine growth restriction is associated with low insulin secretion and a delayed development of the insulin-producing B-cells. These perinatal alterations may induce a deficient adaptation of the endocrine pancreas and insulin resistance in later life. Intrauterine growth restriction in human pregnancy is mainly due to a reduced uteroplacental blood flow or to maternal undernutrition or malnutrition. However, intrauterine growth restriction can be present in severe diabetes complicated by vasculopathy and nephropathy. In animal models, intrauterine growth retardation can be obtained through pharmacological (streptozotocin), dietary (semi-starvation, low protein diet) or surgical (intrauterine artery ligation) manipulation of the maternal animal. The endocrine pancreas and more specifically the insulin-producing B-cells play an important role in the adaptation to an adverse intrauterine milieu and the consequences in later life. The long-term consequences of an unfavourable intrauterine environment are of major importance worldwide. Concerted efforts are needed to explore how these long-term effects can be prevented. This review will consist of two parts. In the first part, we discuss the long-term consequences in relation to the development of the fetal endocrine pancreas and fetal growth in the human; in the second part, we focus on animal models with disturbed fetal and pancreatic development and the consequences for later life. (+info)
Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring.
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Dietary protein restriction during gestation has been shown to produce vascular dysfunction in pregnant rats and hypertension in their offspring. However, no studies have to date examined the effects of such 'programming' on the vascular function of female offspring when they in turn become pregnant. We have therefore studied isolated conduit and resistance artery function from pregnant female offspring of control (C, 18 % casein) and protein-restricted (PR, 9 % casein) pregnant dams. There were no differences in birth weight, weight gain during pregnancy, litter size, fetal weight, placental weight, fetal : placental weight ratio or organ weights between the C and PR groups. In isolated mesenteric arteries, the vasodilatation in response to the endothelial-dependent vasodilator acetylcholine (ACh) and the beta-adrenoceptor agonist isoprenaline was decreased in the PR group, while there were no differences in the constriction in response to potassium (125 mM) or the alpha1-adrenoceptor agonist phenylephrine (PE). No differences in any responses were seen in the isolated thoracic aorta. We conclude that dietary protein restriction in pregnancy programmes vasodilator dysfunction in isolated resistance arteries of female offspring when they become pregnant, but does not affect conduit arteries. (+info)
The dangerous road of catch-up growth.
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Many epidemiological studies have now shown a strongly increased risk of developing type 2 diabetes and the metabolic syndrome in adults who as neonates showed signs of poor early (fetal and early postnatal) growth. The thrifty phenotype hypothesis was proposed to provide a conceptual and experimentally testable basis of these relationships. We have used protein restriction of rat dams, as a means to test this hypothesis. In vivo and in vitro studies of the growth-restricted offspring of such pregnancies have provided findings showing remarkable parallels with the human conditions. Permanent changes in the expression of regulatory proteins in liver, muscle and adipose tissue provide at least part of the explanation of the changes observed and offer potential markers for testing in the human context. These studies have also raised the question as to whether 'catch up' growth following early growth retardation may add to the risks posed by this early handicap. Male rats growth-retarded during fetal life and cross-fostered shortly after birth to normal lactating dams reach normal body and organ weights by weaning but have a reduced longevity. This finding raises the possibility that catch up growth, whilst potentially beneficial in the short term, may be detrimental to long-term survival. Human epidemiological studies may point in the same direction. Work by others on other models of early growth restriction have produced similar, although more limited, data. These findings raise the interesting possibility that the response to fetal stress, be it nutritional or other, may evoke a somewhat restricted and uniform pattern of adaptive response. (+info)
Placental glucose transport in growth-restricted pregnancies induced by overnourishing adolescent sheep.
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Glucose clamp procedures were used to determine whether the slowing of fetal growth during the final third of gestation in overnourished adolescent ewes is due to a reduction in placental glucose transport capacity. Singleton pregnancies to a single sire were established by embryo transfer and thereafter adolescent dams were offered a high (n = 11) or moderate (n = 7) nutrient intake. Studies were conducted at 130 +/- 0.5 days gestation. Uterine and umbilical blood flows were studied by the steady-state transplacental diffusion technique and glucose fluxes quantified by the Fick principle. To determine the relationship between the transplacental glucose gradient and umbilical (fetal) glucose uptake, studies were conducted with maternal arterial glucose clamped at 5 micromol ml(-1) and fetal glucose at spontaneously occurring and two additional higher levels. Maternal body weight gain during gestation averaged 282 and 57 g day(-1) for high- and moderate-intake dams, respectively. Total placentome weight (209 +/- 23 vs. 386 +/- 34 g) and fetal weight (3072 +/- 266 vs. 4670 +/- 196 g) were lower (P < 0.001) in high- than in moderate-intake groups. The growth-restricted pregnancies in the high-intake dams were associated with reduced uterine (P < 0.05) and umbilical (P < 0.02) blood flows and, in the non-perturbed state, the fetuses were relatively hypoxic (2.1 vs. 3.0 micromol ml(-1), P < 0.05) and hypoglycaemic (0.90 vs. 1.31 micromol ml(-1), P < 0.002). Linear regression analysis of umbilical glucose uptake at three steady-state uterine-umbilical arterial transplacental plasma glucose concentration gradients revealed that absolute placental glucose transport capacity was lower in high- than in moderate-intake dams (mean slope, 0.8 vs. 1.5 dl min(-1), P < 0.05; and mean intercept, 1.84 vs. 3.40 micromol ml(-1)). However, glucose transfer capacity was not different between the two groups when expressed on a placental weight-specific basis. This confirms that the small size of the placenta per se is the major limitation to placental glucose transfer in the overnourished adolescent pregnant sheep. (+info)
Multiple micronutrient supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation: a randomized controlled trial in a semirural community in Mexico.
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BACKGROUND: Little is known about the benefits of prenatal multivitamin and mineral supplements in reducing low birth weight. OBJECTIVE: We conducted a randomized, double-blind clinical trial in semirural Mexico to compare the effects of multiple micronutrient (MM) supplements with those of iron supplements during pregnancy on birth size. DESIGN: Pregnant women (n = 873) were recruited before 13 wk of gestation and received supplements 6 d/wk at home, as well as routine antenatal care, until delivery. Both supplements contained 60 mg Fe, but the MM group also received 1-1.5 times the recommended dietary allowances of several micronutrients. RESULTS: At recruitment, the women in the 2 groups were not significantly different in age, parity, economic status, height, or hemoglobin concentration but differed significantly in marital status (4.6% and 2.0% of women in the MM and iron-only groups, respectively, were single mothers) and mean (+/- SD) body mass index (in kg/m(2); 24.6 +/- 4.3 and 23.8 +/- 3.9 in the iron-only and MM groups, respectively). Losses to follow-up (25%) and compliance (95%) did not differ significantly between the groups. In intent-to-treat analyses (MM group: n = 323; iron-only group: n = 322), mean (+/- SD) birth weight (2.981 +/- 0.391 and 2.977 +/- 0.393 kg in the MM and iron-only groups, respectively) and birth length (48.61 +/- 1.82 and 48.66 +/- 1.83 cm in the MM and iron-only groups, respectively) did not differ significantly between the groups. CONCLUSION: These findings suggest that MM supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation. (+info)
Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial.
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BACKGROUND: Iron deficiency anemia (IDA) is common in pregnant women, but previous trials aimed at preventing IDA used high-dose iron supplements that are known to cause gastrointestinal side effects. OBJECTIVE: The objective was to assess the effect on maternal IDA and iron deficiency (ID, without anemia) of supplementing pregnant women with a low dosage (20 mg/d) of iron. Effects on iron status were assessed at the time of delivery and at 6 mo postpartum. Gastrointestinal side effects were assessed at 24 and 36 wk of gestation. DESIGN: This was a randomized, double-blind, placebo-controlled trial of a 20-mg daily iron supplement (ferrous sulfate) given from 20 wk of gestation until delivery. RESULTS: A total of 430 women were enrolled, and 386 (89.7%) completed the follow-up to 6 mo postpartum. At delivery, fewer women from the iron-supplemented group than from the placebo group had IDA [6/198, or 3%, compared with 20/185, or 11%; relative risk (RR): 0.28; 95% CI: 0.12, 0.68; P < 0.005], and fewer women from the iron-supplemented group had ID (65/186, or 35%, compared with 102/176, or 58%; RR: 0.60; 95% CI: 0.48, 0.76; P < 0.001). There was no significant difference in gastrointestinal side effects between groups. At 6 mo postpartum, fewer women from the iron-supplemented group had ID (31/190, or 16%, compared with 51/177, or 29%; RR: 0.57; 95% CI: 0.38, 0.84; P < 0.005). The rate of IDA between the groups did not differ significantly at 6 mo postpartum. CONCLUSION: Supplementing the diet of women with 20 mg Fe/d from week 20 of pregnancy until delivery is an effective strategy for preventing IDA and ID without side effects. (+info)