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.     

Influence of exercise training on maternal and fetal morphological characteristics in the rat

Evidence in both humans and animals has shown that exercise before or during pregnancy may effect fetal outcome. The purpose of this investigation was to examine the effects of an exercise program on fetal development in the rat. Prior to impregnation one group of animals was exercise-trained on a Quinton shock-stimulus rodent treadmill. The exercised group was trained to run 5 days/wk, for 2.0 h/day at 31 m/min up an 8 degree incline for 8 wk before mating. Following mating the training intensity was reduced to 27 m/min up a 5 degree incline, and the exercise period decreased to 1 h/day. On day 19 of gestation, 24 h postexercise for the trained mothers, the animals were killed in the fed state and the maternal and fetal characteristics were measured. The sedentary controls gained significantly (P less than 0.05) more body weight during pregnancy. This can be attributed to three factors: higher number of fetuses, 14.83 +/- 0.04 vs. 12.2 +/- 0.85 for the trained; larger litter weights, 44.25 +/- 4.97 vs. 26.17 +/- 1.82 g/dam for the trained; and slightly larger lipid stores. In addition to having fewer pups the trained mothers had a greater number of fetal resorptions; 0.9/dam as opposed to 0.17/dam for the sedentary control. Analysis of fetal body composition showed no difference in total body water, protein, or fat between the pups of sedentary and trained dams. The results of this study indicate that exercise training prior to and during pregnancy influences fetal development in the rat.     

Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep

Pregnancy is associated with a significant increase in uteroplacental blood flow (UBF), which is responsible for delivering adequate nutrients and oxygen for fetal and placental growth. The present study was designed to determine the effects of vascular insufficiency on fetal and placental growth. Thirty-nine late-term pregnant ewes were instrumented to investigate the effects of chronic UBF reduction. Animals were split into three groups based on uterine blood flow, and all animals were killed on gestational day 138. UBF, which began at 851 +/- 74 ml/min (n = 39), increased in controls (C) to 1,409 +/- 98 ml/min (day 138 of gestation) and in the moderately restricted (R(M)) group to 986 +/- 69 ml/min. In the severely restricted (R(S)) group, UBF was only 779 +/- 79 ml/min on gestational day 138. This reduction in UBF significantly affected fetal body weight with R(M) fetuses weighing 3,685 +/- 178 g and R(S) fetuses weighing 2,920 +/- 164 g compared with C fetal weights of 4,318 +/- 208 g. Fetal brain weight was not affected, whereas ponderal index was significantly reduced in R(M) (2.94 +/- 0.09) and R(S) fetuses (2.49 +/- 0.08) compared with the value of the C fetuses (3.31 +/- 0.08). Placental weight was also significantly reduced in the R(M) group, being 302 +/- 24 g, whereas the R(S) group placenta weighed 274 +/- 61 g compared with the C values of 414 +/- 57 g. Fetal heart, liver, lung, and thymus were all significantly smaller in the R(S) group. Thus the present study shows a clear relationship between the level of UBF and both fetal and placental size. Furthermore, the observation that fetal brain weight was not affected, whereas fetal body weight was significantly reduced suggests that this experimental preparation may provide a useful model in which to study asymmetric fetal growth restriction.     

Fetal metabolism and placental transfer of vasoactive intestinal peptide in sheep

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid putative neurotransmitter that may have a role in the regulation of myometrial blood flow and uterine contractility. The chronically cannulated fetal sheep preparation was used to examine the fetal clearance and placental transfer of VIP. Metabolic Clearance Rate (MCR) and placental transfer of VIP were measured by alternate steady-state infusion of VIP into the mother and fetus. Plasma concentrations of VIP were measured by radioimmunoassay. MCR was similar in the pregnant (45 +/- 10 ml/kg/min) and nonpregnant ewes (35 +/- 5 ml/kg/min). However, compared to both pregnant and nonpregnant ewes, fetal MCR was significantly increased at 77 +/- 15 ml/kg/min, indicating highly developed clearance mechanisms in the fetus. VIP did not cross the placenta in either direction. Both the placenta and fetal liver metabolized VIP and contributed to the elevated fetal clearance of VIP. The results show that VIP in fetal tissue is unlikely to influence maternal uterine activity with any VIP-mediated effects emanating from maternal and/or placental sources.     

Effects on fetal and maternal body temperatures of exposure of pregnant ewes to heat, cold, and exercise.

We exposed Dorper-cross ewes at approximately 120-135 days of gestation to a hot (40 degrees C, 60% relative humidity) and a cold (4 degrees C, 90% relative humidity) environment and to treadmill exercise (2.1 km/h, 5 degrees gradient) and measured fetal lamb and ewe body temperatures using previously implanted abdominal radiotelemeters. When ewes were exposed to 2 h of heat or 30 min of exercise, body temperature rose less in the fetus than in the mother, such that the difference between fetal and maternal body temperature, on average 0.6 degrees C before the thermal stress, fell significantly by 0.54 +/- 0.06 degrees C (SE, n = 8) during heat exposure and by 0.21 +/- 0.08 degrees C (n = 7) during exercise. During 6 h of maternal exposure to cold, temperature fell significantly less in the fetus than in the ewe, and the difference between fetal and maternal body temperature rose to 1.16 +/- 0.26 degrees C (n = 9). Thermoregulatory strategies used by the pregnant ewe for thermoregulation during heat or cold exposure appear to protect the fetus from changes in its thermal environment.     

Uterine blood flow, oxygen and glucose uptakes at mid-gestation in the sheep

In early ovine fetal development, the placenta grows more rapidly than the fetus so that at mid-gestation the aggregate weight of placental cotyledons exceeds fetal weight. The purpose of this study was to compare two separate methods of measuring uterine blood flow and glucose and oxygen uptakes in seven mid-gestation ewes, each carrying a single fetus. Uterine blood flow to both uterine horns was measured by microsphere and by tritiated water steady-state diffusion methodology. Calculations of tritiated water blood flows and oxygen and glucose uptakes were based on measurements of arteriovenous concentration differences across each uterine horn. The distribution of blood flow and oxygen uptake between the two uterine horns was strongly correlated with placental mass distribution. The two methods gave comparable results for uterine blood flow (457 +/- 35 vs 476 +/- 35 ml/min), oxygen uptake (457 +/- 35 vs 476 +/- 35 mumol/min), and glucose uptake (63 +/- 8 vs 64 +/- 6 mumol/min). Uterine blood flow was approximately 38% of the late gestation value and 56.1 +/- 1 times higher than umbilical blood flow. Uteroplacental oxygen consumption was about 58% of late gestation measurements and 3.9 +/- 0.5 times higher than fetal oxygen uptake. We confirm that the large placental mass of mid-gestation is associated with high levels of maternal placental blood flow and placental oxidative metabolism.     

Placental diffusing capacity and its relation to fetal growth.

The placental diffusing capacity for carbon monoxide was measured in unanaesthetized monkeys (M. Mulatta). Maternal and fetal blood was sampled from chronically placed catheters while the mother breathed 50 or 100 parts per million of CO. Diffusing was calculated from the amount of CO taken up by the fetus divided by the partial pressure difference across the placenta, it averaged 0.646 plus or minus 0.062 (SEM) ml x min(-1) x torr(-1) x kg(-1) of fetal weight. The significance of this index of respiratory gas exchange in the monkey placenta is discussed with respect to previous measurements in other species and with respect to fetal growth.     

Fetal insulin and placental 3-O-methyl glucose clearance in near-term sheep

It is difficult, if not impossible, to measure the placental transfer of glucose directly because of placental glucose consumption and the low A-V glucose difference across the sheep placenta. We have approached the problem of quantifying placental hexose transfer by using a nonmetabolized glucose analogue (3-O-methyl glucose) which shares the glucose transport system. We have measured the clearance by using a multisample technique permitting least squares linear computing to avoid the errors implicit in the Fick principle. The placental clearance of 3-O-methyl glucose was measured in the control condition and after the administration of insulin to the fetal circulation. A glucose clamp technique was used to maintain constant transplacental glucose concentrations throughout the duration of the experiment. A control series was performed in which the only intervention was the infusion of normal saline. In these experiments the maternal and fetal glucose concentrations remained constant as did the volume of distribution of 3-O-methyl glucose in the fetus. The maternal insulin concentration remained constant and fetal insulin concentration changed from 11 +/- 2 microU/ml to 355 +/- 51 microU/ml (P less than 0.01). In the face of this large increase in fetal plasma insulin, there was no change in the placental clearance of 3-O-methyl glucose. In the control condition the clearance was 14.1 +/- 1.0 ml/min per kg and this was 13.8 +/- 1.0 ml/min per kg in the high insulin condition. Fetal insulin may change placental glucose flux by decreasing fetal plasma glucose concentrations but does not do so by changing the activity of the glucose transport system.     

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.     

Evaluation of the developmental toxicity of lenalidomide in rabbits

BACKGROUND: Lenalidomide, a thalidomide analog, is indicated for treatment of patients with deletion-5q myelodysplastic syndromes or multiple myeloma. NZW rabbits were used because of sensitivity to thalidomide's teratogenicity. METHODS: Range-finding and pulse-dosing studies preceded a full developmental toxicity study in New Zealand white (NZW) rabbits (25/group) given lenalidomide (0, 3, 10, or 20 mg/kg/day) or thalidomide (180 mg/kg/day) by stomach tube on gestation days (GD) 7-19. Clinical signs, body weights, and feed consumption were recorded daily from GD 7. On GD 29, standard maternal necropsy, uterine content, and fetal evaluations were carried out. RESULTS: In all studies, thalidomide was selectively toxic to development. In the pulse-dosing study, lenalidomide did not affect development at 100 mg/kg/day. Increases in C(max) and AUC(0-24 hr) values for lenalidomide were slightly less than dose-proportional; lenalidomide occurred in the fetuses. At 10 and 20 mg/kg/day, lenalidomide was maternally toxic (reduced body weight gain and feed consumption; at 20 mg/kg/day, weight loss and one abortion). Developmental toxicity at 10 and 20 mg/kg/day included reduced fetal body weights and increased postimplantation losses and fetal variations (morbidity/purple-discolored skin, undeveloped intermediate lung lobe, irregular nasal-frontal suture, and delayed metacarpal ossification). Thalidomide selectively reduced fetal body weight, increased postimplantation loss and caused characteristic limb and other dysmorphology. CONCLUSIONS: The maternal and developmental NOAELs for lenalidomide are 3 mg/kg/day. Unlike thalidomide, lenalidomide affected embryo-fetal development only at maternally toxic dosages, confirming that structure-activity relationships may not predict maternal or developmental effects. No fetal malformations were attributable to lenalidomide.     

Developmental toxicity evaluation of ELF magnetic fields in Sprague-Dawley rats

To identify possible effects of horizontally polarized magnetic field (MF) exposure on maintenance of pregnancy and embryo-fetal development, an MF exposure system was designed and constructed and 96 time-mated female Sprague-Dawley (SD) rats (24/group) received continuous exposure to 60 Hz MF at field strengths of 0 (sham control) and 5, 83.3, or 500 microT (50, 833, or 5000 mG). Dams received MF or sham exposures for 22 h/day on gestational day 6-20. MF was monitored continuously throughout the study. There were no evidences of maternal toxicity or developmental toxicity in any MF exposed groups. Mean maternal body weight, organ weights, and hematological and serum biochemical parameters in groups exposed to MF did not differ from those in sham control. No exposure related differences in fetal deaths, fetal body weight, and placental weight were observed between MF exposed groups and sham control. External, visceral, and skeletal examination of fetuses demonstrated no significant differences in the incidence of fetal malformations between MF exposed and sham control groups. In conclusion, exposure of pregnant rats to 60 Hz at MF strengths up to 500 microT during gestation day 6-20 did not produce any biologically significant effect in either dams or fetuses.     

The role of fetal urinary excretion in the transfer of ethanol into amniotic fluid after maternal administration of ethanol to the near-term pregnant ewe

The objective of this study was to determine whether fetal urinary excretion is a major route of ethanol transfer into the amniotic fluid surrounding the fetus following maternal administration of ethanol. Conscious instrumented pregnant ewes between 130 and 137 days' gestation (term, 147 days) with (n = 3) or without (n = 3) a catheter in the fetal bladder were administered 1 g ethanol/kg maternal body weight as a 1-h maternal intravenous infusion. Maternal blood, fetal blood, and amniotic fluid samples were collected at selected times, and fetal urine was collected continuously from the bladder-cannulated fetus during the 14-h study for the determination of ethanol concentrations. Fetal urinary excretion of ethanol occurred, and the total amount of ethanol excreted represented 0.30 +/- 0.07 (SD)% of the maternal ethanol dose. The renal clearance of ethanol by the fetus was 0.43 +/- 0.06 mL/min. The pharmacokinetics of ethanol in the maternal-fetal unit and the amniotic fluid for the bladder-cannulated fetal preparation were similar to the data for the nonbladder-cannulated preparation. The data indicate that fetal urinary excretion of ethanol is a secondary route of ethanol transfer into the amniotic fluid. It would appear that diffusion of ethanol across membranes from the maternal and fetal circulations is a major route of ethanol transfer into this intrauterine compartment.     

Human maternal and fetal response to graded exercise

Six healthy active women in the third trimester of pregnancy participated in a graded exercise protocol to levels of exertion perceived to be equivalent to that of their usual exercise regimen. Fetal heart rate response (FHR) was documented by ultrasound transducer and confirmed (n = 1) by ultrasonic visualization. Resting maternal O2 consumption was 277 +/- 50 (SD) ml/min and rose to 1,132 +/- 202 ml/min at a mean final exercise intensity of 79 +/- 9 W after 12.8 +/- 1.7 min on a cycle ergometer. There was no significant change in maternal serum insulin, growth hormone, glucose, or pH values. Maternal leukocyte count, hemoglobin, and venous lactate levels rose significantly during the exercise (P less than 0.05). FHR prior to exercise was 142 +/- 4 beats/min and decreased to 84 +/- 34 beats/min during exercise. The decrease in FHR was documented within 1 min of initiating exercise in all cases. During exercise, fetal movements were not accompanied by FHR accelerations. Within 1 min following the cessation of exercise, FHR rose to 143 +/- 8 beats/min and fetal movements were accompanied by FHR accelerations. Since the recovery of FHR occurred immediately after cessation of maternal exercise, this level of maternal exercise does not appear to be harmful to the fetus.     

Maternal insulin and placental 3-O-methyl glucose transport

The effects of insulin in the maternal circulation on the placental clearance of 3-O-methyl glucose were investigated in 7 animals in the presence of a constant maternal glucose concentration. While maternal insulin concentration changed from 12 +/- 4 to 175 +/- 33 mu Units/ml, the placental clearance remained constant at 16.2 +/- 1.2 (control) and 15 +/- 1.3 ml/min per kg fetus under the influence of the insulin. To test the secondary hypothesis that in the control condition the hexose transport system was saturated, we performed a further series of experiments in 6 fasted animals. In these animals the control maternal plasma insulin concentration was 2 +/- 0.3 mu Units/ml and after the infusion of insulin it increased to 562 +/- 26 mu Units/ml. Under conditions of constant maternal and fetal plasma glucose concentrations, this massive elevation of plasma insulin did not change the placental clearance of 3MeG which was 15.2 +/- 1.6 in the control condition and 13.3 +/- ml/min per kg under the influence of high insulin. We conclude that maternal insulin ranging from 2 mu Units/ml to supraphysiologic doses does not effect a physiologically significant change in placental hexose transfer. Placental glucose transfer can probably therefore, be changed only be changing the concentration of glucose in the maternal and fetal plasma.     

Short-term training effects on diastolic function in obese persons with the metabolic syndrome

The aim of this study was to determine the effects of a short-term high-intensity exercise program on diastolic function and glucose tolerance in obese individuals with and without metabolic syndrome (MetSyn). Obese men and women (BMI > 30 kg/m(2); 39-60 years) with and without the MetSyn (MetSyn 13; non-MetSyn 18) underwent exercise training consisting of 10 consecutive days of treadmill walking for 1 h/day at 70-75% of peak aerobic capacity. Subjects performed pre- and post-training testing for aerobic capacity, glucose tolerance (2-h meal test), and standard echocardiography. Aerobic capacity improved for both groups (non-MetSyn 24.0 +/- 1.6 ml/kg/min vs. 25.1 +/- 1.5 ml/kg/min; MetSyn 25.2 +/- 1.8 ml/kg/min vs. 26.2 +/- 1.7 ml/kg/min, P < 0.05). Glucose area under the curve (AUC) improved in the MetSyn group (1,017 +/- 58 pmol/l/min vs. 883 +/- 75 pmol/l/min, P < 0.05) with no change for the non-MetSyn group (685 +/- 54 pmol/l/min vs. 695 +/- 70 pmol/l/min). Isovolumic relaxation time (IVRT) improved in the MetSyn group (97 +/- 6 ms vs. 80 +/- 5 ms, P < 0.05), and remained normal in the non-MetSyn group (82 +/- 6 ms vs. 86 +/- 5 ms). No changes in other diastolic parameters were observed. The overall reduction in IVRT was correlated with a decrease in diastolic blood pressure (DBP) (r = 0.45, P < 0.05), but not with changes in glucose tolerance. Body weight did not change with training in either group. A 10-day high-intensity exercise program improved diastolic function and glucose tolerance in the group with MetSyn. The reduction in IVRT in MetSyn was associated with a fall in blood pressure. These data suggest that it may be possible to reverse early parameters of diastolic dysfunction in MetSyn with a high-intensity exercise program.     

Myogenesis in sheep is altered by maternal feed intake during the peri-conception period

The effect of varying short-term maternal feed intake during the peri-conception period on the development of ovine fetal muscle at mid-gestation was investigated. Superovulated donor Merino ewes (n = 24) were fed a roughage/grain pelleted diet (10.1 MJME/kg dry matter) at either 1.5x maintenance (H; high) or 0.5x maintenance (L; low) from 18 days before until 6 days after ovulation. Embryos were transferred to recipient ewes (n = 60) on day 6. Singleton fetuses were collected on day 75 of gestation and placental weights, fetal body dimensions and fetal organ and muscle weights recorded. The number, type and size of muscle fibres and the dry matter, RNA, DNA and protein content in the semitendinosus muscle were determined. Maternal feed intake did not influence body dimensions, organ development or muscle weights in the fetus. However, L feed intake decreased total muscle fibre number in the fetus by approximately 20% (P = 0.06) compared to H feed intake. This resulted from a reduced secondary to primary fibre ratio (P < 0.05) and indicated that secondary fibre formation occurred at a reduced rate in L fetuses. In addition, protein:DNA ratio tended to be lower in muscles of L fetuses (P < 0.1). It is concluded that restricting feed intake over the peri-conception period reduces or delays myogenesis in fetal sheep. The potential mechanisms by which nutritional availability during this period may influence subsequent myogenic development are discussed.     

Embryonic and fetal development in a commercial dam-line genotype

During depopulation of a breeding unit within Swine Graphics Enterprises, extensive data were collected and used to examine relationships among ovulation rate, the pattern of prenatal loss, and placental and fetal development. Groups of Large White x Landrace females (n=447) were slaughtered between day 20-30, 50-55 or 85-90 of gestation, with approximately equal numbers of animals representing gilts and parity 1 (G/P1), parity 2-3 (P2/3), and parity >4 (P4+). Ovulation rate and embryo number were recorded for all animals. With the exception of the G/P1 animals, embryonic and placental weight were recorded for four conceptuses per sow on day 20-30; on day 85-90 two conceptuses per sow were dissected to determine placental and fetal development. Ovulation rate (22.7 +/- 0.2 overall) was higher (P <0.05) in P2/3 (23.6 +/- 0.4) and P4+ (24.7 +/- 0.4) than in G/P1 (20.2 +/- 0.5). Embryonic/fetal survival was 61.8 +/- 2.1% at day 20-30, 50.2 +/- 2.2% at day 50-55 and 48.7 +/- 1.9% at day 85-90 and the number of surviving conceptuses was higher (P <0.05) in the P2/3 sows than in other parity groups. There was no relationship between ovulation rate and number of live embryos at day 20-30 or 85-90. At day 20-30 and 85-90, embryo weight was positively correlated with placental weight, but neither placental weight nor embryonic/fetal weight was correlated with number of viable embryos. A parity by gestation day interaction existed; placental weight for P4+ (3.42 +/- 0.43 g) was less than for P2/3 (7.55 +/- 0.40 g) at day 20-30 (P <0.0001), whereas at day 85-90, placental weight of P2/3 (209.5 +/- 8.5 g) was less (P=0.05) than both G/P1 (235.7 +/- 7.3g) and P4+ (235.4 +/- 7.1 g). At day 85-90, fetal brain weight, relative to body weight (R2=0.61, P <0.0001), and fetal brain:liver weight ratio (R2=0.35; P <0.0001) were negatively related to mean fetal weight, and brain:liver weight ratio showed a trend towards a relationship with number of viable fetuses (P=0.08). Parity also affected brain:liver weight ratio (P=0.01). Clearly, high ovulation rates in the higher parity sows have the potential to cause excessive in utero crowding of conceptuses in the post-implantation period. Even with moderate crowding, increased brain:liver weight ratios in smaller fetuses in late gestation indicate that uterine capacity impacts fetal development as well as the number of surviving fetuses.     

Matching of maternal and fetal flow ratios in the sheep placenta

Local interaction of maternal and fetal placental blood flows was studied in two groups of unanaesthetized near-term sheep. Five sheep were exposed to a simulated dive to 100 feet of seawater (4.03 atmospheres) for 25 min. Six fetuses received an infusion of noradrenaline (6.8 micrograms/[kg x min]). Radioactive microspheres were administered simultaneously to mother and fetus before (control) and after (test) the experimental manipulation. Maternal and fetal relative activities, defined as % of total placental radioactivity divided by % of total placental weight, were calculated for 1-g pieces of cotyledonary tissue under control and test conditions. Pieces of cotyledons were defined as matched if the direction of change in relative activity from control to test was the same for mother and fetus. In the absence of an interaction between the maternal and fetal placental circulations, the probability of a piece of cotyledon being matched is 0.5. In each series of experiments the proportion of all cotyledon pieces having maternal and fetal relative activities that changed in the same direction was significantly greater than 0.5. Thus, the majority of the placental mass responds to a physical or chemical perturbation of the fetus in such a way that changes in relative perfusion are qualitatively matched in the adjacent maternal and fetal placental circulations.     

Effect of maternal weight gain during pregnancy on exercise performance

We examined the effect of maternal weight gain during pregnancy on exercise performance. Ten women performed submaximal cycle (up to 60 W) and treadmill (4 km/h, up to 10% grade) exercise tests at 34 +/- 1.5 (SD) wk gestation and 7.6 +/- 1.7 wk postpartum. Postpartum subjects wearing weighted belts designed to equal their body weight during the antepartum tests performed two additional treadmill tests. Absolute O2 uptake (VO2) at the same work load was higher during pregnancy than postpartum during cycle (1.04 +/- 0.08 vs. 0.95 +/- 0.09 l/min, P = 0.014), treadmill (1.45 +/- 0.19 vs. 1.27 +/- 0.20 l/min, P = 0.0002), and weighted treadmill (1.45 +/ 0.19 vs. 1.36 +/- 0.20 l/min, P = 0.04) exercise. None of these differences remained, however, when VO2 was expressed per kilogram of body weight. Maximal VO2 (VO2max) estimated from the individual heart rate-VO2 curves was the same during and after pregnancy during cycling (1.96 +/- 0.37 to 1.98 +/- 0.39 l/min), whereas estimated VO2max increased postpartum during treadmill (2.04 +/- 0.38 to 2.21 +/- 0.36 l/min, P = 0.03) and weighted treadmill (2.04 +/- 0.38 to 2.19 +/- 0.38 l/min, P = 0.03) exercise. We conclude that increased body weight during pregnancy compared with the postpartum period accounts for 75% of the increased VO2 during submaximal weight-bearing exertion in pregnancy and contributes to reduced exercise capacity. The postpartum increase in estimated VO2max during weight-bearing exercise is the result of consistently higher antepartum heart rates during all submaximal work loads.     

Dose–Response Effects of Diphenylhydantoin on Pregnant Dams and Embryo‐Fetal Development in Rats

Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose–response relationship of DPH. This study investigated the dose–response effects of DPH on pregnant dams and embryo‐fetal development as well as the relationship between maternal and developmental toxicity. DPHwas orally administered to pregnant rats from gestational days 6 through 15 at 0, 50, 150, and 300 mg/kg/day. At 300 mg/kg, maternal toxicity including increased clinical signs, suppressed body weight, decreased food intake, and increased weights of adrenal glands, liver, kidneys, and brain were observed in dams. Developmental toxicity, including a decrease in fetal and placental weights, increased incidence of morphological alterations, and a delay in fetal ossification delay also occurred. At 150 mg/kg, maternal toxicity manifested as an increased incidence of clinical signs, reduced body weight gain and food intake, and increased weights of adrenal glands and brain. Only minimal developmental toxicity, including decreased placental weight and an increased incidence of visceral and skeletal variations, was observed. No treatment‐related maternal or developmental effects were observed at 50 mg/kg. These results show that DPH is minimally embryotoxic at a minimal maternotoxic dose (150 mg/kg/day) but is embryotoxic and teratogenic at an overt maternotoxic dose (300 mg/kg/day). Under these experimental conditions, the no‐observed‐adverse‐effect level of DPH for pregnant dams and embryo‐fetal development is considered to be 50 mg/kg/day. These data indicate that DPH is not a selective developmental toxicant in the rat.