Maternal DDAVP-induced hyponatremia preserves fetal urine flow during acute fetal hemorrhage

Maternal administration of DDAVP induces maternal and fetal plasma hyponatremia, accentuates fetal urine flow, and increases amniotic fluid volume. Fetal hemorrhage represents an acute stress that results in fetal AVP secretion and reduced urine flow rate. In view of the potential therapeutic use of DDAVP for pregnancies with reduced amniotic fluid volume, we sought to examine the impact of maternal hypotonicity during acute fetal hemorrhage. Chronically catheterized pregnant ewes (130 +/- 2 days) were allocated to control or to DDAVP-induced hyponatremia groups. In the latter group, tap water (2,000 ml) was administered intragastrically to the ewe followed by DDAVP (20 microg bolus, 4 microg/h) and a maintenance intravenous infusion of 5% dextrose water for 4 h to achieve maternal hyponatremia of 10-12 meq/l. Thereafter, ovine fetuses from both groups were continuously hemorrhaged to 30% of estimated blood volume over a 60-min period. DDAVP caused similar degree of reductions in plasma sodium and osmolality in pregnant ewes and their fetuses. In response to hemorrhage, DDAVP fetuses showed greater reduction in hematocrit than control fetuses (14 vs. 10%). Both groups of fetuses demonstrated similar increases in plasma AVP concentration. However, the AVP-hemorrhage threshold was greater in DDAVP fetuses (22.5%) than in control (17.5%). Hemorrhage had no significant impact on plasma osmolality, electrolyte levels, or cardiovascular responses in either group of fetuses. Despite similar increases in plasma AVP, DDAVP fetuses preserved fetal urine flow rates, with values threefold those of control fetuses. These results suggest that under conditions of acute fetal stress of hemorrhage, maternal DDAVP may preserve fetal urine flow and amniotic fluid volume.     

Exercise responses in pregnant sheep: blood gases, temperatures, and fetal cardiovascular system

In an effort to examine the effects of maternal exercise on the fetus we measured maternal and fetal temperatures and blood gases and calculated uterine O2 consumption in response to three different treadmill exercise regimens in 12 chronically catheterized near-term sheep. We also measured fetal catecholamine concentrations, heart rate, blood pressure, cardiac output, blood flow distribution, blood volume, and placental diffusing capacity. Maternal and fetal temperatures increased a mean maximum of 1.5 +/- 0.5 (SE) and 1.3 +/- 0.1 degrees C, respectively. We corrected maternal and fetal blood gas values for the temperatures in vivo. Maternal arterial partial pressure of O2 (PO2), near exhaustion during prolonged (40 min) exercise at 70% maximal O2 consumption, increased 13% to a maximum of 116.7 +/- 4.0 Torr, whereas partial pressure of CO2 (PCO2) decreased by 28% to 27.6 +/- 2.2 Torr. Fetal arterial PO2 decreased 11% to a minimum of 23.2 +/- 1.6 Torr, O2 content by 26% to 4.3 +/- 0.6 ml X dl -1, PCO2 by 8% to 49.6 +/- 3.2 Torr, but pH did not change significantly. Recovery was virtually complete within 20 min. During exercise total uterine O2 consumption was maintained despite the reduction in uterine blood flow because of hemoconcentration and increased O2 extraction. The decrease of 3 Torr in fetal arterial PO2 and 1.5 ml X dl -1 in O2 content did not result in major cardiovascular changes or catecholamine release. These findings suggest that maternal exercise does not represent a major stressful or hypoxic event to the fetus.     

Rat alpha-fetoprotein in experimental utero-placental ischaemia.

Retardation of growth and death of fetal rats were produced after uteroplacental ischaemia was induced by surgical ligation of the uterine arteries. Changes in maternal plasma levels of alpha-fetoprotein (AFP) were measured by radioimmunoassay. In rats in which the uterine blood supply was totally occluded, the resultant increase in maternal plasma AFP was due to resorption of fetal elements, because AFP levels in maternal rat plasma did not increase following hysterectomy in a control group. Maternal plasma AFP levels in rats with a partly occluded blood supply (and therefore some dead and some live fetuses) paralleled those of sham-operated rats, suggesting that increased placental transfer of AFP to maternal plasma may have offset the anticipated decline of AFP due to a decreased number of live fetuses.     

Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans.

We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.     

The influence of gestational age and onset of labour on determinants of fetal-maternal fluid and electrolyte balance in sheep.

Our aim was to compare the effects of gestational age and the timing of the onset of labour on factors influencing fetal fluid and electrolyte balance and urine production in fetal sheep. We measured the volume and composition of fetal urine and amniotic and allantoic fluids, as well as fetal and maternal plasma composition and micturition episodes in sheep during late gestation until the onset of labour. We found that daily fetal urine production and urethral urine flow per micturition episode increased significantly in relation to the onset of labour but not to gestational age (P < 0.05). In the 2 days preceding the onset of labour fetal urine and amniotic fluid K+ concentrations and urine osmolality increased significantly and the Na+/K+ ratio in allantoic fluid decreased significantly (P < 0.05). There was also a significant fall in fetal arterial SaO2 (P < 0.05) but no significant changes occurred in fetal plasma electrolyte composition, osmolality or AVP concentrations. Fetal plasma cortisol and prolactin concentrations and amniotic and allantoic fluid prolactin concentrations increased significantly and progressively in association with both advancing gestation and the onset of labour whereas maternal plasma prolactin concentrations increased significantly only in the 2 days before the onset of labour (P < 0.05). We conclude that some developmental aspects of fetal fluid and electrolyte balance, including renal function, are more closely related to the timing of parturition than to gestational age per se.     

Does Antenatal Maternal Psychological Distress Affect Placental Circulation in the Third Trimester?

Introduction

Some types of antenatal maternal psychological distress may be associated with reduced fetal growth and birthweight. A stress-mediated reduction in placental blood flow has been suggested as a mechanism. Previous studies have examined this using ultrasound-derived arterial resistance measures in the uterine (UtA) and umbilical (UA) arteries, with mixed conclusions. However, a reduction in placental volume blood flow may occur before changes in arterial resistance measures are seen. Fetoplacental volume blood flow can be quantified non-invasively in the umbilical vein (UV). Our objective was to study whether specific types of maternal psychological distress affect the placental circulation, using volume blood flow quantification in addition to arterial resistance measures.

Methods

This was a prospective observational study of 104 non-smoking pregnant women (gestational age 30 weeks) with uncomplicated obstetric histories. Psychological distress was measured by General Health Questionnaire-28 (subscales anxiety and depression) and Impact of Event Scale-22 (subscales intrusion, avoidance and arousal). UtA and UA resistance measures and UV volume blood flow normalized for fetal abdominal circumference, were obtained by Doppler ultrasound.

Results

IES intrusion scores above the mean were associated with a reduction in normalized UV volume blood flow (corresponding to –0.61 SD; P = 0.003). Adjusting for UA resistance increased the strength of this association (difference –0.66 SD; P<0.001). Other distress types were not associated with UV volume blood flow. Maternal distress was not associated with arterial resistance measures, despite adjustment for confounders.

Conclusions

Intrusive thoughts and emotional distress regarding the fetus were associated with reduced fetoplacental volume blood flow in third trimester. Uterine and umbilical artery resistance measures were not associated with maternal distress. Our findings support a decrease in fetoplacental blood flow as a possible pathway between maternal distress and reduced fetal growth.     

Chronic alterations in ovine maternal corticosteroid levels influence uterine blood flow and placental and fetal growth

Previous work from this laboratory demonstrated that the elevation of maternal plasma corticosteroid concentrations during pregnancy is important for the support of fetal development. Reducing ovine maternal plasma cortisol concentrations to nonpregnant levels stimulates homeostatic responses that defend fetal blood volume. The present study was designed to test the hypothesis that chronic decreases or increases in maternal plasma cortisol concentration alter uterine and placental blood flow and morphology. Three groups of pregnant ewes and their fetuses were chronically catheterized and studied: ewes infused with cortisol (1 mg.kg(-1).day(-1); high cortisol), ewes adrenalectomized and underreplaced with cortisol (0.5 mg.kg(-1).day(-1); low cortisol), and control ewes. The normal increment in uterine blood flow between 120 and 130 days was eliminated in the low-cortisol ewes; conversely, uterine blood flow was increased in the high-cortisol group compared with the control group. Fetal arterial blood pressure was increased in the high-cortisol group compared with controls, but there was no increase in fetal arterial pressure from 120 to 130 days of gestation in the low-cortisol group. The fetuses of both low-cortisol and high-cortisol groups had altered placental morphology, with increased proportions of type B placentomes, and overall reduced fetal placental blood flow. The rate of fetal somatic growth was impaired in both low-cortisol and high-cortisol groups compared with the fetuses in the intact group. The results of this study demonstrate that maternal plasma cortisol during pregnancy is an important contributor to the maternal environment supporting optimal conditions for fetal homeostasis and somatic growth.     

Enkephalin peptides in fetal sheep, changes with gestation, origin and production by the placenta.

Enkephalin-containing peptides have been followed in the circulation of fetal sheep between 118-143 days gestation. Using a combination of radioimmunoassay and hplc met5-enkephalin was found in the concentration range 60-500 pg/ml and proenkephalins containing met5-enkephalin had a concentration of 150-4000 pg/ml. The concentration of both increased towards term. The sources of the enkephalin peptides was investigated by measurement of differences across the umbilical circulation and by studying the effects of fetal adrenal demedullation and chemical sympathectomy. The placenta showed a continuous net output of enkephalin peptides which increased close to term. This placental output was increased sharply by reduction of uterine blood flow either using compression of the uterine artery or through infusion of adrenaline at 35 micrograms/min into the maternal circulation. Maternal hypoxia caused by breathing 9% O2 plus 3% CO2 also increased fetal plasma enkephalin levels, although not output from the placenta. Adrenal demedullation, particularly if accompanied by chemical sympathectomy depressed fetal plasma enkephalin concentrations and sharply suppressed the fetal peptide responses to maternal hypoxia. It is concluded that the placenta and the fetal adrenal are important sources of met5-enkephalin-containing peptides in the fetal circulation. The placental production appears to be closely tied to changes in uterine perfusion and adrenal output changes in response to fetal oxygenation.     

Maternal dehydration: impact on ovine amniotic fluid volume and composition

Maternal dehydration consistent with mild water deprivation or moderate exercise results in maternal and fetal plasma hyperosmolality and increased plasma arginine vasopressin (AVP). Previous studies have demonstrated a reduction in fetal urine and lung fluid production in response to maternal dehydration or exogenous fetal AVP. As fetal urine and perhaps lung liquid combine to produce amniotic fluid, maternal dehydration may affect the amniotic fluid volume and/or composition. In the present study, six chronically-prepared pregnant ewes with singleton fetuses (128 +/- 1 day) were water deprived for 54 h to determine the effect on amniotic fluid. Maternal plasma osmolality (306.5 +/- 0.9 to 315.6 +/- 1.9 mOsm/kg) and AVP (1.9 +/- 0.2 to 22.2 +/- 3.2 pg/ml) significantly increased during dehydration. Similarly, fetal plasma osmolality (300.0 +/- 0.9 to 312.7 +/- 1.7 mOsm/kg) and AVP (1.4 +/- 0.1 to 10.4 +/- 2.4 pg/ml) increased in parallel to maternal values. Amniotic fluid osmolality (276.8 +/- 5.7 to 311.6 +/- 6.5 mOsm/kg) and sodium (139.8 +/- 4.8 to 154.0 +/- 5.4 mEq/l) and potassium (9.1 +/- 1.3 to 13.9 +/- 2.4 mEq/l) concentrations increased while a significant (35%) reduction in amniotic fluid volume occurred (871 +/- 106 to 520 +/- 107 ml). These results indicate that maternal dehydration may have marked effects on maternal-fetal-amniotic fluid dynamics, possibly contributing to the development of oligohydramnios.     

Effects of acute and prolonged exposure to heat on regional blood flows in pregnant sheep

This study deals with fetal growth retardation in heat-exposed sheep, and provides information on mechanisms of acclimation to heat. Radioactive microspheres were used to measure regional capillary blood flows in conscious sheep 80-100 days pregnant, at first in a thermoneutral environment, next after 2.5-6 h exposure to a hot environment of 40 degrees C, 25 mmHg water vapour pressure, and then 7 days and 15-20 days later, after spending 9 h daily in the heat. Maternal blood flow in the placental cotyledons was decreased by the first heat exposure, and remained depressed during the period of periodic heating. Reduction in placental blood flow on the maternal side could be part of the mechanism by which fetal development is retarded in heat-stressed sheep. Acclimation to heat was indicated by a decrease in the rate of rise in rectal temperature during the first 2 h of daily exposure to heat. Concomitantly, there was a progressive increase in the blood flow in extremity skin and nasal mucosa, which are tissues concerned with facilitation of heat loss during acute heat stress. However, in respiratory muscles which are also concerned with heat-loss, there was no further increase in flow after the initial response to to acute heat, indicating that heat acclimation is not due to an increased ability to pant. Blood flow in other tissues such as gut, pancreas and adipose tissue progressively decreased. These changes in blood flow have possible adaptive significance.     

Role of maternal glucocorticoid inducible kinase SGK1 in fetal programming of blood pressure in response to prenatal diet

Maternal stress and malnutrition modify intrauterine fetal development with impact on postnatal blood pressure, nutrient, water, and electrolyte metabolism. The present study explored the possible involvement of maternal serum- and glucocorticoid-inducible kinase (SGK)-1 in fetal programming of blood pressure. To this end, wild-type (sgk1(+/+)) male mice were mated with SGK1 knockout (sgk1(-/-)) female mice, and sgk1(-/-) males with sgk1(+/+) females, resulting in both cases in heterozygotic (sgk1(-/+)) offspring. Following prenatal protein restriction, the offspring of sgk1(+/+) mothers gained weight significantly slower and had significantly higher blood pressure after birth. Moreover, a sexual dimorphism was apparent in fasting blood glucose and plasma corticosterone concentrations, with higher levels in female offspring. In contrast, prenatal protein restriction of sgk1(-/-) mothers had no significant effect on postnatal weight gain, blood pressure, plasma glucose concentration, or corticosterone levels, irrespective of offspring sex. Plasma aldosterone concentration, urinary flow rates, and urinary excretions of Na(+) and K(+) were not significantly modified by either maternal genotype or nutritional manipulation. In conclusion, maternal signals mediated by SGK1 may play a decisive role in fetal programming of hypertension induced by prenatal protein restriction.     

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia

Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10–20%), but ABCA1-mediated efflux was decreased (by 20–35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples (P< 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia (P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia (P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis.     

Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation

Reduced transport of amino acids from mother to fetus can lead to fetal intrauterine growth restriction (IUGR). The activities of several amino acid transport systems, including system A, are decreased in placental syncytiotrophoblast of IUGR pregnancies. Na(+)-K(+)-ATPase activity provides an essential driving force for Na(+)-coupled system A transport, is decreased in the placenta of IUGR pregnancies, and is decreased by angiotensin II in several tissues. Several reports have shown activation of the fetoplacental renin-angiotensin system (RAS) in IUGR. We investigated the effect of angiotensin II on placental system A transport and Na(+)-K(+)-ATPase activity in placental villi. Placental system A activity in single primary villous fragments was measured as the Na(+)-dependent uptake of alpha-(methylamino)isobutyric acid, and Na(+)/K(+) ATPase activity was measured as ouabain-sensitive uptake of (86)rubidium. Angiotensin II decreased system A activity in a concentration-dependent fashion (10-500 nmol/l). Angiotensin II type 1 receptor (AT1-R) antagonists losartan and AT1-R anti-peptide blocked the angiotensin II effect, but the angiotensin II type 2 receptor antagonist PD-123319 was without effect. System A activity was not altered by preincubation with AT1-R-independent vasoconstrictors, and antioxidants did not prevent the decrease in activity mediated by angiotensin II. Angiotensin II decreased Na(+)-K(+)-ATPase activity by an AT1-R dependent mechanism, and inhibition of Na(+)-K(+)-ATPase activity decreased system A activity in a dose-response fashion. These data suggest that angiotensin II, via AT1-R signaling, decreases system A activity by suppressing Na(+)-K(+)-ATPase in human placental villi, consistent with possible adverse effects of enhanced placental RAS on fetal growth.     

Effects of restricting uteroplacental blood flow on concentrations of corticotrophin-releasing hormone, adrenocorticotrophin, cortisol, and prostaglandin E2 in the sheep fetus during late pregnancy.

We have examined the effects of reduced uterine blood flow and prolonged fetal hypoxemia on the temporal relationship between changes in hormones associated with the activity of the pituitary-adrenal axis (corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), cortisol, and prostaglandin E2 (PGE2) in the ovine fetus at 120-125 days of pregnancy, and we sought evidence for placental secretion of CRH and ACTH during prolonged hypoxemia. Uterine blood flow was reduced by placing an adjustable Teflon clamp around the maternal common internal iliac artery to decrease fetal arterial oxygen saturation from mean values of 59.1 +/- 3.3 to 25.7 +/- 4.6% (+/- SEM, n = 10). There was a transient peak in immunoreactive (IR-) CRH at 1-2 h after reducing uterine blood flow. IR-ACTH rose to peak values at +2 h, then gradually decreased to control level by +12 h. Fetal plasma cortisol and PGE2 concentrations were elevated significantly by +2 and +4 h, respectively, and at 20-24 h. The identity of IR-CRH in fetal plasma and in ovine placental extracts was confirmed by HPLC, but there was no consistent umbilical vein--femoral arterial concentration difference for either IR-CRH or IR-ACTH during normoxemia or hypoxemia. We conclude that a sequence of endocrine changes involving CRH, ACTH, PGE2, and cortisol occurs in the fetus during a prolonged reduction in uterine blood flow. However, we did not obtain evidence, for placental secretion of either CRH or ACTH in response to this manipulation.     

Placental Underperfusion in a Rat Model of Intrauterine Growth Restriction Induced by a Reduced Plasma Volume Expansion

Lower maternal plasma volume expansion was found in idiopathic intrauterine growth restriction (IUGR) but the link remains to be elucidated. An animal model of IUGR was developed by giving a low-sodium diet to rats over the last week of gestation. This treatment prevents full expansion of maternal circulating volume and the increase in uterine artery diameter, leading to reduced placental weight compared to normal gestation. We aimed to verify whether this is associated with reduced remodeling of uteroplacental circulation and placental hypoxia. Dams were divided into two groups: IUGR group and normal-fed controls. Blood velocity waveforms in the main uterine artery were obtained by Doppler sonography on days 14, 18 and 21 of pregnancy. On day 22 (term = 23 days), rats were sacrificed and placentas and uterine radial arteries were collected. Diameter and myogenic response of uterine arteries supplying placentas were determined while expression of hypoxia-modulated genes (HIF-1α, VEGFA and VEGFR2), apoptotic enzyme (Caspase -3 and -9) and glycogen cells clusters were measured in control and IUGR term-placentas. In the IUGR group, impaired blood velocity in the main uterine artery along with increased resistance index was observed without alteration in umbilical artery blood velocity. Radial uterine artery diameter was reduced while myogenic response was increased. IUGR placentas displayed increased expression of hypoxia markers without change in the caspases and increased glycogen cells in the junctional zone. The present data suggest that reduced placental and fetal growth in our IUGR model may be mediated, in part, through reduced maternal uteroplacental blood flow and increased placental hypoxia.     

Maternal and cord blood ghrelin in the pregnancies of smoking mothers: possible markers of nutrient availability for the fetus

AIMS: To investigate the role of ghrelin in maternal and fetal metabolism, we determined its value in maternal smoking, a specific cause of reduced placenta function and fetal growth. METHODS: In 85 normal term pregnancies, 42 in smoking and 43 in non-smoking mothers, we measured ghrelin in the maternal blood at the onset of labor and in the cord blood of their 85 singletons immediately after birth. We determined the relationships between ghrelin and placental GH (PGH), pituitary GH (pitGH), and IGF-I. RESULTS: The newborns of smoking mothers weighed 0.24 kg less (p < 0.05) than those of non-smoking mothers. Cord blood ghrelin was 71% higher and PGH and cord blood IGF-I were 34% and 32% lower, respectively, in the pregnancies of smoking compared with non-smoking mothers (p < 0.05). Cord blood ghrelin was unrelated to pitGH and cord blood IGF-I. Maternal ghrelin was unchanged in smoking mothers, increased with maternal fasting duration (r = 0.26, p < 0.05), showed no correlation with PGH and negative correlation with cord blood IGF-I (r = -0.42, p < 0.01). CONCLUSION: The decrease in placental function and fetal growth in smoking mothers is associated with an increase in cord blood ghrelin, and no change in maternal ghrelin. Maternal ghrelin concentration increases with fasting, and is negatively correlated with cord blood IGF-I: it may signal a reduction in the level of nutrients available for placental transfer. No correlation supports a role for ghrelin in PGH or pitGH secretion.     

Lack of maternal to fetal transfer of 125I-labelled erythropoietin in sheep.

We administered tracer quantities of biologically active 125I-labelled recombinant human erythropoietin by intravenous bolus injection to seven late gestation pregnant ewes. Maternal and fetal blood was sampled over the subsequent six hours and assayed for erythropoietin-specific radioactivity. Despite the expected increase in maternal plasma immunoprecipitable 125I-labelled erythropoietin radioactivity, fetal plasma levels remained unchanged throughout the study. In addition, erythropoietin receptors were not detected in ovine and human placental tissue. We conclude that biologically active 125I-labelled erythropoietin does not cross the placenta from mother to fetus in measurable quantities in sheep, and likely in humans. Thus, these data indicate the levels of erythropoietin measured in fetal plasma are reflective of fetal, and not maternal, erythropoietin production and elimination.     

The effect of maternal fluid intake on the volume and composition of fetal urine

The effects on fetal renal function of restricting maternal water intake to 1 l/day for 6 days was investigated in 7 chronically-catheterized fetuses (gestation age 118-131 days). Restriction of water intake caused a significant decrease in maternal urine flow rate and significant increases in maternal plasma and urinary osmolality. Fetal renal function was investigated on the third and sixth days of the period of restricted maternal intake of water. Urine flow rate from the fetus was depressed significantly, and urinary osmolality increased significantly. The glomerular filtration rate remained unchanged, and free water clearance was decreased. These changes indicate increased water reabsorption in the distal parts of the nephron, probably consequent upon increased circulating levels of antidiuretic hormone. In 3 fetuses whose mothers subsequently had free access to water, these changes in urine flow rate and free water clearance that occurred during water restriction were reversed. There was an inverse correlation between maternal plasma osmolality and fetal free water clearance corrected for glomerular filtration rate. It is concluded that when water intake by a pregnant animal is restricted, the availability of water to the fetus is reduced and fetal sheep respond by producing a concentrated urine.     

Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep

The global incidence of human obesity has more than doubled over the past three decades. An ovine model of obesity was developed to determine effects of maternal obesity and arginine supplementation on maternal, placental, and fetal parameters of growth, health, and well being. One-hundred-twenty days prior to embryo transfer, ewes were fed either ad libitum (n?=?10) to induce obesity or 100% National Research Council-recommended nutrient requirements (n?=?10) as controls. Embryos from superovulated ewes with normal body condition were transferred to the uterus of control-fed and obese ewes on day 5.5 post-estrus to generate genetically similar singleton pregnancies. Beginning on day 100 of gestation, obese ewes received intravenous administration of saline or L-arginine-HCl three times daily (81?mg arginine/kg?body?weight/day) to day 125, whereas control-fed ewes received saline. Fetal growth was assessed at necropsy on day 125. Maternal obesity increased (1) percentages of maternal and fetal carcass lipids and (2) concentrations of leptin, insulin, glucose, glutamate, leucine, lysine and threonine in maternal plasma while reducing (1) concentrations of progesterone, glycine and serine in maternal plasma and (2) amniotic and allantoic fluid volumes. Administration of L-arginine to obese ewes increased arginine and ornithine concentrations in maternal and fetal plasma, amniotic fluid volume, protein content in maternal carcass, and fetal brown adipose tissue (+60%), while reducing maternal lipid content and circulating leptin levels. Fetal or placental weight did not differ among treatments. Results indicate that arginine treatment beneficially reduces maternal adiposity and enhances fetal brown adipose tissue development in obese ewes.     

Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig

Small size at birth has been associated with an increased risk of central obesity and reduced lean body mass in adult life. This study investigated the time of onset of prenatally induced obesity, which occurs after maternal feed restriction, in the guinea pig, a species that, like the human, develops substantial adipose tissue stores before birth. We examined the effect of maternal feed restriction [70% ad libitum intake from 4 wk before to midpregnancy, then 90% until day 60 gestation (term approximately 69 days)] on fetal growth and body composition in the guinea pig. Maternal feed restriction reduced fetal (-39%) and placental (-30%) weight at 60 days gestation and reduced liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while relative weights of brain, lungs, and interscapular and retroperitoneal fat pads were increased. In the interscapular depot, maternal feed restriction decreased the volume density of multilocular fat and increased that of unilocular fat, resulting in an increased relative weight of interscapular unilocular fat. Maternal feed restriction did not alter the relative weight of perirenal fat or the volume density of adipocyte populations within the depot but increased unilocular lipid locule size. Maternal feed restriction in the guinea pig is associated with decreased weight of major organs, including liver and skeletal muscle, but increased adiposity of the fetus, with relative sparing of unilocular adipose tissue. If this early-onset obesity persists, it may contribute to the metabolic and cardiovascular dysfunction that these offspring of feed-restricted mothers develop as adults.