Maternal nutrition in early and late pregnancy in relation to placental and fetal growth.

OBJECTIVE: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. DESIGN: Prospective observational study. SETTING: Princess Anne Maternity Hospital, Southampton. SUBJECTS: 538 mothers who delivered at term. MAIN OUTCOME MEASURES: Placental and birth weights adjusted for the infant''s sex and duration of gestation. RESULTS: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g(95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother''s height and body mass index and of strong relations between the mother''s birth weight and the placental and birth weights of her offspring. CONCLUSION: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring''s risk of cardiovascular disease.     

Glucose transporter isoform-3 mutations cause early pregnancy loss and fetal growth restriction

Glucose transporter isoform-3 (GLUT3) is the trophoblastic facilitative glucose transporter. To investigate the role of this isoform in embryonic development, we created a novel GLUT3-null mouse and observed arrested early embryonic development and loss at neurulation stage when both alleles were mutated. This loss occurred despite the presence of other related isoforms, particularly GLUT1. In contrast, when a single allele was mutated, despite increased embryonic cell apoptosis, adaptive changes in the subcellular localization of GLUT3 and GLUT1 in the preimplantation embryo led to postimplantation survival. This survival was compromised by decreased GLUT3-mediated transplacental glucose transport, causing late-gestation fetal growth restriction. This yielded young male and female adults demonstrating catch-up growth, with normal basal glucose, insulin, insulin-like growth factor-I and IGF-binding protein-3 concentrations, fat and lean mass, and glucose and insulin tolerance. We conclude that GLUT3 mutations cause a gene dose-dependent early pregnancy loss or late-gestation fetal growth restriction despite the presence of embryonic and placental GLUT1 and a compensatory increase in system A amino acid placental transport. This critical life-sustaining functional role for GLUT3 in embryonic development provides the basis for investigating the existence of human GLUT3 mutations with similar consequences during early pregnancy.     

Isoprostanes in amniotic fluid: a predictive marker for fetal growth restriction in pregnancy

Isoprostanes are markers of free radical-catalyzed lipid peroxidation. Evidence suggests that oxidative stress occurs in pregnancies with fetal growth restriction (FGR). The aim of this study was to analyze F2-isoprostanes in amniotic fluid of FGR pregnancies. We tested the hypothesis that F2-isoprostanes are reliable markers to distinguish FGR pregnancies from normal ones and appropriate-for-gestational-age (AGA) from small-for-gestational-age (SGA) newborns. F2-isoprostanes levels were measured by colorimetric enzyme immunoassay in the amniotic fluid of 77 pregnancies with normal fetal growth (group I) and 37 with FGR (group II). Fetal biometry and Doppler measurements were obtained using an ATL HDI 3000 ultrasound system. Isoprostanes were higher in group II than group I. The ROC curve distinguished group I from group II, showing 100% sensitivity and 88.3% specificity at a cutoff of 94 pg/ml. There were no statistical differences in isoprostanes levels between AGA and SGA newborns in group II. The area under the ROC curve drawn to distinguish AGA and SGA newborns showed a sensitivity of 100% and a specificity of 72.3% at a cutoff of 94 pg/ml. The relative risk index indicated a 8.05 times higher risk of birth weight below the 3rd percentiles in group II than in group I. High isoprostanes concentrations can be detected in the amniotic fluid of FGR pregnancies and the assay of isoprostanes in amniotic fluid is a reliable assessment of fetal oxidative stress. Common use of this predictive marker in obstetrics will improve the ability of clinicians to identify those fetuses who will be born SGA or with a birth weight below the 25th percentile.     

Intrauterine growth restriction alters the hepatic proteome in fetal pigs

Intrauterine growth restriction (IUGR) is a major problem in both humans and animals. The IUGR fetus has abnormal metabolism of nutrients in the liver. This study was conducted with comparative proteomic approach and biochemical analyses to test the hypothesis that IUGR alters the hepatic proteome in the fetal liver. Livers were obtained from IUGR and normal-weight fetal pigs at Day 110 of gestation. Twenty-two differentially expressed proteins in the liver were identified between IUGR and normal fetal pigs. These proteins participate in the intermediary metabolism of nutrients (including glucose, amino acids, protein, lipids, vitamins and minerals), oxidative stress, as well as cell structure and growth. Of particular interest, the IUGR fetus had a higher activity of glutamate oxaloacetate transaminase and a lower activity of lipoprotein lipase than the normal ones. These results indicate altered metabolism of nutrients, abnormal ammonia utilization, and reduced capacity for detoxification in the liver of IUGR fetus. Collectively, the findings have important implication for explaining low food efficiency and understanding the mechanism responsible for impaired growth in IUGR neonates.     

Low dietary protein during early pregnancy alters bovine placental development

To determine if low dietary protein concentration in the first two trimesters of pregnancy alters placental development, genetically similar heifers from closed herd were fed diets containing different levels of protein in the first and second trimesters of gestation. There were four animals per treatment group, the groups being: L/L = fed a diet containing 7% crude protein (CP) (low protein) in the first and second trimesters; H/H = fed a diet containing 14% CP (high protein) in the first and second trimesters; L/H = fed low protein in the first trimester and high in the second trimester and vice versa for the H/L group. Low protein diets in the first trimester increased dry cotyledon weight at term. Trophectoderm' volume density increased in the H/L and L/H group compared to the L/L and H/H groups. Blood vessel volume and volume density in foetal villi decreased in the H/L and L/H groups compared with the H/H and L/L groups. There was no effect of diet treatment on cotyledon number, diameter or wet weight and no effect on the volume density of connective tissue or fibroblasts in the foetal villi. These results show that a low dietary protein concentration in the first trimester of pregnancy followed by increased protein in the second trimester enhanced placental development. Further, trophectoderm volume was highly correlated with birth weight. Early protein restriction in the pregnant cow may enhance foetal growth in part by stimulating placental growth and function.     

Effect of restriction of placental growth on fetal and utero-placental metabolism

The effect of restriction of placental growth on the supply of glucose to the gravid uterus and fetus and on fetal and utero-placental metabolism of glucose and lactate was examined in this study. Endometrial caruncles were removed from 13 sheep (caruncle sheep) prior to mating, which restricted placental growth in the subsequent pregnancy. Half the fetuses of caruncle sheep were small or growth retarded, with the remainder normal in size. After insertion of vascular catheters at 110 days gestation, the caruncle sheep, together with 16 control sheep, were studied between 121 and 130 days of gestation. Glucose delivery to and consumption by the gravid uterus and its contents, both as a total and per kg of tissue mass, was significantly lower in caruncle ewes with small fetuses, although glucose extraction was similar to that in controls. Utero-placental glucose consumption was significantly lower in caruncle ewes carrying small fetuses compared to that in control ewes, both as a total and per kg of placenta. Small caruncle fetuses were hypoxaemic and hypoglycaemic and the lactate concentration in the common umbilical vein was significantly higher than in control sheep. Glucose delivery to and consumption by the fetus was significantly lower in normal-sized and in small caruncle fetuses compared to controls. Fetal glucose consumption per kg of fetus was similar in control and caruncle sheep. Fetal glucose extraction increased as fetal weight decreased. Utero-placental production of lactate was similar in control and caruncle ewes. However, uterine output of lactate decreased as placental weight fell. Utero-placental production of lactate per kg of placenta was significantly higher in caruncle ewes compared to controls and increased as oxygen content in blood from the fetal femoral artery decreased. Fetal lactate consumption per kg of fetus increased as the concentration of lactate in blood from the common umbilical vein increased. It is concluded that intrauterine growth retardation due to restriction of placental growth is associated with a reduced supply of glucose to both the pregnant uterus and fetus and a redistribution of glucose therein to the fetus, both directly as glucose and indirectly as lactate. This reflects the disproportionate maintenance of fetal weight relative to that of the placenta, reduced utero-placental consumption of glucose per kg of placenta, conversion of a greater proportion of that glucose or other substrate(s) to lactate by the placenta and an increase in the fraction of the lactate produced by utero-placental tissues that is secreted into the fetal circulation.     

Supplementation with high-dose cholecalciferol throughout pregnancy induces fetal growth restriction through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition

Vitamin D deficiency has been associated with adverse pregnant outcomes. Several studies investigated the effects of maternal vitamin D3 supplementation on fetal development with inconsistent results. The aim of this study was to investigate the effects of maternal supplementation with different doses of vitamin D3 on fetal development. Pregnant mice were administered with different doses of cholecalciferol (0, 2,000, 10,000, 40,000 IU/kg/day) by gavage throughout pregnancy. Fetal weight and crown-rump length were measured. Placental proliferation and mesenchymal characteristics were detected. HTR-8/SVneo cells were incubated in the absence or presence of calcitriol (500 nmol/L) to evaluate the effects of active vitamin D3 on migration and invasion of human trophoblast cells. Although a low dose of cholecalciferol was safe, fetal weight and crown-rump length were decreased in dams treated with high-dose cholecalciferol throughout pregnancy. Placental weight and labyrinth thickness were reduced in mice administered with high-dose cholecalciferol. An obvious calcification was observed in placentae of mice administered with high-dose cholecalciferol. Ki67-positive cells, a marker of placental proliferation, were reduced in mice administered with high-dose cholecalciferol. N-cadherin and vimentin, two mesenchymal markers, were decreased in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. MMP-2 and MMP-9, two matrix metalloproteinases, were downregulated in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. In addition, trophoblast migration and invasion were suppressed by calcitriol. Supplementation with high-dose cholecalciferol induces fetal growth restriction partially through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition.     

Indices of oxidative stress in pregnancy with fetal growth restriction

Intrauterine fetal growth restriction (IUGR), the main cause of premature delivery and fetal mortality, has been suggested to involve oxidative stress. We found elevated values of indices of oxidative stress in the blood serum of pregnant women with IUGR: increased levels of malondialdehyde and 4-hydroxyalkenals, decreased activity of alpha-1-antitrypsin and decreased total antioxidant capacity of the serum, with respect to healthy pregnancy. Twenty day treatment with 3 g of l-arginine and 75 mg of acetylsalicylic acid daily resulted in a decrease of the level of lipid peroxidation products and augmentation of alpha-1-antitrypsin activity. This study confirms the occurrence of oxidative stress in IUGR and demonstrates the beneficial effect of arginine/acetylsalicylic acid therapy in reducing oxidative stress in IUGR.     

Indices of oxidative stress in pregnancy with fetal growth restriction

Intrauterine fetal growth restriction (IUGR), the main cause of premature delivery and fetal mortality, has been suggested to involve oxidative stress. We found elevated values of indices of oxidative stress in the blood serum of pregnant women with IUGR: increased levels of malondialdehyde and 4-hydroxyalkenals, decreased activity of α-1-antitrypsin and decreased total antioxidant capacity of the serum, with respect to healthy pregnancy. Twenty day treatment with 3 g of l-arginine and 75 mg of acetylsalicylic acid daily resulted in a decrease of the level of lipid peroxidation products and augmentation of α-1-antitrypsin activity. This study confirms the occurrence of oxidative stress in IUGR and demonstrates the beneficial effect of arginine/acetylsalicylic acid therapy in reducing oxidative stress in IUGR.     

Human placental transthyretin in fetal growth restriction in combination with preeclampsia and the HELLP syndrome

Fetal growth restriction is a serious, still poorly understood pregnancy-related pathology often associated with preeclampsia. Recent studies speculate on the role of human transthyretin, a carrier protein for thyroxin and retinol binding protein, in the etiology of both pregnancy pathologies. Objective was to investigate the localization and abundance of transthyretin (TTR) in placentas of pregnancies suffering from fetal growth restriction with and without preeclampsia and HELLP. This was a retrospective case control study on human paraffin-embedded placentas from pregnancies with a gestational age at delivery between the 24th and 34th week of gestation. 16 placentas were included in this study, 11 cases and 5 from normotensive pregnancies as controls. Cases were divided into three groups: four from early onset idiopathic intrauterine growth restriction (IUGR), four from early-onset severe preeclampsia (PE), and three from early-onset IUGR with preeclampsia plus HELLP syndrome. Distribution and abundance of TTR were investigated by means of immunohistochemistry. Semi quantitative analysis of TTR staining of placental sections revealed that TTR was mostly expressed in the villous trophoblast covering placental villi. Only weak staining of TTR in villous stroma could be detected. The comparison of placentas revealed that in pure IUGR and severe PE there is a much stronger TTR reactivity compared to controls and cases with IUGR?+?PE?+?HELLP. Concluding, the study showed that TTR is dysregulated in cases of IUGR and severe early onset preeclampsia. Interestingly, TTR expression is not affected in cases with HELLP syndrome that reveal the same staining intensities as age-matched controls.     

Inhibition of placental ornithine decarboxylase by DL-alpha-difluoro-methyl ornithine causes fetal growth restriction in rat

The roles of polyamines in intrauterine growth restriction (IUGR) is studied. The DL-alpha-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) which is a rate limiting enzyme of polyamine synthesis was administrated to pregnant rats so that we obtained rat fetuses with IUGR. The changes of maternal nutrition, damage of the placenta, and the direct effect of DFMO on the fetus were examined in this IUGR model. Administration of DFMO did not induced changes of maternal nutrition except for triglyceride and the fetal metabolic state. But the placental weight, ODC activity, and DNA in the placenta were decreased significantly. The ODC activity in the total placenta decreased to less than 10% of that of the control. Depression of ODC activity in the placenta may be the major cause of IUGR induced by DFMO administration, and polyamines play important roles to carry pregnancy.     

Maternal and fetal placental growth hormone and IGF axis in type 1 diabetic pregnancy

Aim

Placental growth hormone (PGH) is a major growth hormone in pregnancy and acts with Insulin Like Growth Factor I (IGF-I) and Insulin Like Growth Hormone Binding Protein 3 (IGFBP3). The aim of this study was to investigate PGH, IGF-I and IGFBP3 in non-diabetic (ND) compared to Type 1 Diabetic (T1DM) pregnancies.

Methods

This is a prospective study. Maternal samples were obtained from 25 ND and 25 T1DM mothers at 36 weeks gestation. Cord blood was obtained after delivery. PGH, IGF-I and IGFBP3 were measured using ELISA.

Results

There was no difference in delivery type, gender of infants or birth weight between groups. In T1DM, maternal PGH significantly correlated with ultrasound estimated fetal weight (r = 0.4, p = 0.02), birth weight (r = 0.51, p<0.05) and birth weight centile (r = 0.41, p = 0.03) PGH did not correlate with HbA1c.Maternal IGF-I was lower in T1DM (p = 0.03). Maternal and fetal serum IGFBP3 was higher in T1DM. Maternal third trimester T1DM serum had a significant band at 16 kD on western blot, which was not present in ND.

Conclusion

Maternal T1DM PGH correlated with both antenatal fetal weight and birth weight, suggesting a significant role for PGH in growth in diabetic pregnancy.IGFBP3 is significantly increased in maternal and fetal serum in T1DM pregnancies compared to ND controls, which was explained by increased proteolysis in maternal but not fetal serum. These results suggest that the normal PGH-IGF-I-IGFBP3 axis in pregnancy is abnormal in T1DM pregnancies, which are at higher risk of macrosomia.     

Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP

During pregnancy, parathyroid hormone-related protein (PTHrP) is one of many growth factors that play important roles to promote fetal growth and development, including stimulation of placental calcium transport. Angiotensin II, acting through the AT(1a) receptor, is also known to promote placental growth. We examined the effects of bilateral uterine artery and vein ligation (restriction), which mimics placental insufficiency in humans, on growth, intrauterine PTHrP, placental AT(1a), and pup calcium. Growth restriction was surgically induced on day 18 of pregnancy in Wistar-Kyoto female rats by uterine vessel ligation. Uteroplacental insufficiency reduced fetal body weight by 15% and litter size (P < 0.001) compared with the control rats with no effect on placental weight or amniotic fluid volume. Uteroplacental insufficiency reduced placental PTHrP content by 46%, with increases in PTHrP (by 2.6-fold), parathyroid hormone (PTH)/PTHrP receptor (by 11.6-fold), and AT(1a) (by 1.7-fold) relative mRNA in placenta following restriction compared with results in control (P < 0.05). There were no alterations in uterine PTHrP and PTH/PTHrP receptor mRNA expression. Maternal and fetal plasma PTHrP and calcium concentrations were unchanged. Although fetal total body calcium was not altered, placental restriction altered perinatal calcium homeostasis, as evidenced by lower pup total body calcium after birth (P < 0.05). The increased uterine and amniotic fluid PTHrP (P < 0.05) may be an attempt to compensate for the induced impaired placental function. The present study demonstrates that uteroplacental insufficiency alters intrauterine PTHrP, placental AT(1a) expression, and perinatal calcium in association with a reduction in fetal growth. Uteroplacental insufficiency may provide an important model for exploring the early origins of adult diseases.     

Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction

Using a mid- to late-gestation ovine model of intrauterine growth restriction (IUGR), we examined uteroplacental blood flow and fetal growth during melatonin supplementation as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% [adequate; (ADQ)] or 60% [restricted (RES)] of nutrient requirements until day 130 of gestation. Umbilical artery blood flow was increased from day 60 to day 110 of gestation in MEL vs. CON dams, while umbilical artery blood flow was decreased from day 80 to day 110 of gestation in RES vs. ADQ dams. At day 130 of gestation, uteroplacental hemodynamics, measured under general anesthesia, and fetal growth were evaluated. Uterine artery blood flow was decreased in RES vs. ADQ dams, while melatonin supplementation did not affect uterine artery blood flow. Total placentome weight and placentome number were not different between treatment groups. Fetal weight was decreased by nutrient restriction. Abdominal girth and ponderal index were increased in fetuses from MEL-ADQ dams vs. all other groups. Fetal biparietal distance was decreased in CON-RES vs. CON-ADQ dams, while melatonin supplementation rescued fetal biparietal distance. Fetal kidney length and width were increased by maternal melatonin treatment. Fetal cardiomyocyte area was altered by both maternal melatonin treatment and nutritional plane. In summary, melatonin may negate the consequences of IUGR during specific abnormalities in umbilical blood flow as long as sufficient uterine blood perfusion is maintained during pregnancy.     

Ultrasound evidence of early fetal growth restriction after maternal malaria infection

Background

Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation.

Methodology/Principal Findings

In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001–10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (n = 336) and were not (n = 3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; −0.57 (1.13) versus −0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (p = 0.01) were also independently associated with a smaller BPD in multivariate analysis.

Conclusions/Significance

Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy.     

Effect of heat stress on ovine placental growth in early pregnancy.

Ditocous Dorset ewes were fed to predicted requirements and kept in environmental chambers at 21 degrees C (n = 6) or 40 degrees C (n = 5) between days 50 and 75 of gestation. Ewes were slaughtered and the pregnant uterus was dissected for measurement of conceptus weights and in vitro estimations of placental mitotic activity. Heat caused a 19% reduction in placental weight but did not affect fetal weight. Placental DNA and protein concentrations and protein/DNA were similar in both groups. Total placental DNA content was significantly reduced in the heated ewes, suggesting a reduction in cell number; however, DNA synthetic rate tended to be higher. These results are consistent with the hypothesis that fetal growth retardation in chronically heat-stressed ewes occurs in late pregnancy as a consequence of a primary reduction in placental growth in early gestation.     

Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi--associations with placental malaria and fetal growth restriction

Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM.     

Maternal nutrient restriction during placental growth,programming of fetal adiposity and juvenile blood pressure control

Epidemiological and experimental studies have demonstrated that maternal undernutrition during pregnancy is associated with abnormal placental growth. In sheep, maternal nutrient restriction over the period of rapid placental growth (30-80 days) restricts placentome growth. Then following adequate nutrition up to term (147 days), placental mass is greater in association with a higher total abundance of the predominant placental glucose transporter-1. The resulting lambs are larger at birth, have heavier kidneys with an increased expression of the glucocorticoid-responsive type 1 angiotensin II receptor. Near to term, these fetuses possess more adipose tissue, the endocrine sensitivity of which is markedly enhanced. For example, the abundance of mRNA for 11beta-hydroxysteroid dehydrogenase type 1, which catalyses the conversion of cortisone to bio-active cortisol is increased. This is associated with a higher abundance of both leptin and glucocorticoid receptor mRNA. At 6 months of age, the juvenile offspring of nutrient restricted ewes have lower resting blood pressure that was positively correlated with plasma cortisol concentration, suggesting their blood pressure could be more strongly driven by circulating cortisol. These offspring also exhibited a greater pressor response to vasoconstrictor challenges, but showed no difference in vasodilatory response. At this age, the kidney weight was similar between groups, but the abundance of cytochrome c in kidney mitochondria was enhanced in lambs born to nutrient restricted ewes that could indicate increased mitochondrial activity. Reduced maternal nutrition during the period of rapid placental growth may therefore contribute to hypertension in later life through physiological and vascular adaptations during fetal life.     

Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep

Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or mother may contribute to this growth restriction. We hypothesized that an episode of acute ethanol exposure, mimicking binge drinking would restrict fetal growth and perturb the maternal and fetal IGF axes. Pregnant sheep were infused intravenously with saline or ethanol (1 g/kg maternal wt) over 1 h, on days 116, 117, and 118 of gestation (start of 1st infusion = time 0, term is 147 days). Maternal and fetal plasma IGF and IGF-binding protein (IGFBP) concentrations were measured before and after each infusion. Compared with controls, ethanol exposure reduced fetal weight at day 120 by 19%, transiently reduced maternal plasma IGF-I (-35%) at 30 h, and decreased fetal plasma IGF-II (-28%) from 24 to 54 h after the first infusion. Ethanol exposure did not alter maternal or fetal plasma concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting. We conclude that suppression of maternal and fetal IGF abundance may contribute to fetal growth restriction induced by acute or binge ethanol exposure.