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.     

Insulin-like growth factors in fetal macrosomia with and without maternal diabetes

Insulin-like growth factors (IGFs/somatomedins) have been implicated as regulators of fetal growth. This study investigates whether IGFs are related to macrosomia in infants of normal or insulin-dependent diabetic mothers. Cord concentrations of IGF-I (radioimmunoassay), total IGF (radioreceptor assay) and IGF binding protein (radiobinding assay) were measured in 15 term infants of diabetic mothers (IDM) and 29 term infants of nondiabetic mothers. In infants of control mothers cord IGF and total IGF levels were significantly higher in large-for-gestational-age than appropriate-for-gestational-age infants; but this relationship was lost in IDM, in whom IGF-I concentrations were similar to control infants. IGF binding protein levels were not significantly different in any of these groups. The absence of elevated IGF levels in macrosomic IDM indicates that the pathologic process does not involve a simple increase in these growth factors.     

Effect of alcoholization upon the maternal and fetal hepatic DNA and the maternal serum-proteins in pregnant albino rats

Experiments were performed on pregnant albino rats (Wistar strain) of 150-200 g b.w. Biochemical investigations involved the determination of maternal and fetal hepatic DNA content (Spirin's method), of maternal serum proteins (total protein content and electrophoretic fractions). The mean litter size, early resorptions, fetal mortality, and some biochemical data of fetuses were also determined. The main statements were as follows: The chronic, peroral administration of 20% ethanol to pregnant albino rats before and during pregnancy induced changes of the biosynthesis of hepatic DNA: a nonsignificant increase as compared with the control group was recorded. The control of serum proteins revealed an increase of the total protein content and of the total electrophoretic serumglobulin fractions. Within the globulin fraction, a hyper-alpha-globulinemia, and a hypo-beta and gamma globulinemia were detected. In the fetuses of the experimental group a slight but statistically significant increase of the hepatic DNA content appeared. In the experimental group the early resorption rate (10.97%) and the fetal mortality (2.43%) was increased in comparison with the control group (0%). In the alcoholized mothers a nonsignificant decrease of the crown-rump length and a significant decrease of fetal and placental weight could be observed.     

Effects of maternal exercise on liver and skeletal muscle glycogen storage in pregnant rats.

To examine the effects of maternal exercise on liver and skeletal muscle glycogen storage, female Sprague-Dawley rats were randomly divided into control, nonpregnant runner, pregnant nonrunning control, pregnant runner, and prepregnant exercised control groups. The exercise consisted of treadmill running at 30 m/min on a 10 degree incline for 60 min, 5 days/wk. Pregnancy alone, on day 20 of gestation, decreased maternal liver glycogen content and increased red and white gastrocnemius muscle glycogen storage above control values (P less than 0.05). In contrast, exercise in nonpregnant animals augmented liver glycogen storage and also increased red and white gastrocnemius glycogen content (P less than 0.05). By combining exercise and pregnancy, the decrease in liver glycogen storage in the pregnant nonexercised condition was prevented in the pregnant runner group and more glycogen was stored in both the red and white portions of the gastrocnemius than all other groups (P less than 0.05). Fetal body weight was greatest (P less than 0.05) in the pregnant runner group and lowest (P less than 0.05) in the prepregnant exercise control group. These results demonstrate that chronic maternal exercise may change maternal glycogen storage patterns in the liver and skeletal muscle with some alteration in fetal outcome.     

Reactive oxygen species in pregnant rats: effects of exercise and thermal stress

With the aim of evaluating the effect of interaction between physical training or exercise only during pregnancy and thermal stress on oxidative stress, and antioxidant mechanism sedentary pregnant rats (PS), exercised pregnant rats only during pregnancy (PE) and trained rats submitted to also exercise during pregnancy (PT) were compared (N=63). Exercise sessions consisted of swimming at 80% of maximal work load supported into water at 28 degrees C (hypothermia, PS 28, PE28, PT28) or 35 degrees C (thermal neutrality, PS35, PE35, PT35) or 39 degrees C (hyperthermia, PS39, PE39, PT39), for 30 min. The initial body weight in all groups of rats was from 177 to 207 g. On the 20th day of pregnancy, 24 h after the last immersion or swimming session venous blood was collected to determine oxidative stress. Plasma concentrations of means malondialdehyde (MDA) values measured as thiobarbituric acid reactive substances (TBARS); total glutathione (GSH) and vitamin E were determined. The oxidative stress index was calculated from the ratio TBARS/GSH and TBARS/Vitamin E. TBARS did not change on the group PE at different temperatures of water; TBARS were higher for PS28 than PS35 and PS39; PT35 had higher values than PT28 and PT39. For GSH, PS39 was lower than PS35; PE28 was higher than PE35 and PE39 and PT35 were lower than PT28 and PT39. Plasma concentration of vitamin E did not present any difference for sedentary rats at different water temperatures, but for PE28, the values were lower than for PE35 and PE39, whereas PT39 was lower than PT35 and PT28. In relation to TBARS/GSH, it was verified an increase in oxidative stress for PS28 (in relation to PS35 and PS39), PE35, and PT35 (in relation to PE28 and PE39 or PT28 and PT39); regarding the ratio TBARS/vitamin E, the highest values were obtained at 35 degrees C for PS and PT groups and at 39 for PE group. These results have shown the great complexity of the interaction between physical training, thermal stress and pregnancy. Apparently, hypothermia produces large index of oxidative stress only in sedentary rats, but this index was greater at 35 degrees C in relation to extreme temperatures for trained rats. These results have suggested that physical training allows a more efficient activation of antioxidant mechanisms under thermal stress.     

Effects of exercise on maternal glycogen storage patterns and fetal outcome in mature rats.

The purpose of the present study was to examine the effects of exercise on maternal glycogen storage patterns and fetal outcome in mature (approximately 12 months of age) Sprague-Dawley rats. The exercise consisted of treadmill running at 30 m.min-1, on a 10 degree incline, for 60 min, 5 days per week, for 4 weeks prior to pregnancy, which continued until day 19 of gestation. In mature animals, chronic exercise increased (p < 0.05) liver glycogen concentration in both pregnant and nonpregnant rats. In pregnant exercised animals, the glycogen concentration of the maternal liver increased almost twofold (p < 0.05) compared with the sedentary pregnant group. There was no difference in the amount of glycogen stored in the gastrocnemius or soleus muscles in response to training, pregnancy, or chronic maternal exercise in the mature rat. In the pregnant groups, there were fewer (p < 0.05) viable fetuses and more (p < 0.05) resorption sites than in young rats. In addition, exercise during pregnancy in the mature animal decreased (p < 0.05) fetal body weight. These results demonstrate that a conflict may exist between maternal exercise and fetal demands for energy in the mature rat. This conflict seems to favour the maternal system, as evidenced by the enhanced maternal liver glycogen storage and the negative effect on fetal growth.     

Effects of strenuous maternal exercise on fetal organ weights and skeletal muscle development in rats

The purpose of the present study was to observe the effects of strenuous maternal aerobic exercise throughout gestation on fetal outcome in the rat. The strenuous exercise intensity consisted of a treadmill speed of 30 m.min-1 on a 10 degrees incline, for 120 min.day-1, 5 days.week-1. The rats were conditioned to run on a motor-driven treadmill by following a progressive two-week exercise program, so that by the end of the two weeks the rats were capable of running comfortably at this strenuous intensity in the non-pregnant state. Following the two-week running programme, the rats were paired by weight and randomly assigned to either a pregnant group that continued the running program throughout gestation (pregnant runner), or a pregnant group that did not continue the running program throughout pregnancy (pregnant control). At birth the neonates born to the pregnant running group did not differ in average neonatal body weight values, number per litter or total litter weight values when compared to controls, nor were superficial gross abnormalities observed in neonates born to the pregnant control or pregnant running groups. The strenuous maternal exercise intensity did not alter neonatal organ weight values (brain, heart, liver, lung, kidney), nor neonatal skeletal muscle (gastrocnemius, sternomastoid, diaphragm) when compared to control values. It is suggested that maternal exercise of this intensity throughout gestation does not affect fetal outcome in the rat, and may be due to the animals accustomization to the strenuous exercise protocol prior to pregnancy.     

Localization of glycogen in the placenta and fetal and maternal livers of cadmium-exposed diabetic pregnant rats

This study was designed to investigate the effects of Cd exposure on the glycogen localization in the placenta and in fetal and maternal livers in streptozotocin (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200–220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups (control, Cd treated, STZ treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously daily with CdCl₂ dissolved in isotonic NaCl, starting at the onset of pregnancy throughout the experiment. Diabetes was induced on d 13 of pregnancy by a single intraperitoneal injection of STZ in the STZ-treated group. In addition to the daily injection of Cd, a single intraperitoneal injection of STZ was also given on d 13 of pregnancy in the Cd+STZ-treated group. The rats received the last injection 24 h before being sacrificed and 10 randomly selected rats in each group were sacrificed on d 15 and d 20 of pregnancy. Blood samples were taken for determination of the serum glucose and insulin levels. Fetal and maternal livers of sacrificed rats in all groups were harvested on d 15 and d 20 of pregnancy, whereas placentas were harvested only on d 20 of pregnancy for histochemical examination. Although both Cd and STZ caused hyperglycemia and decreased insulin secretion, Cd-alone treatment increased the glycogen content only in the placental labyrinth, whereas STZ-alone treatment increased the glycogen content only in the maternal part of the placenta. Increased glycogen localization was observed in both the placental labyrinth and the maternal part of placenta when Cd and STZ were given together. Fetal and meternal livers of control and other treatment groups were not different regarding the glycogen content on d 15 or d 20 of pregnancy. It was concluded that Cd exposure during pregnancy might produce a glycogen localization in the placenta of diabetic rats. However, the function and the mechanisms of increased glycogen contents in the placenta of Cd-exposed pregnant diabetic rats remain unclear and further studies are needed.     

Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat

Increased uterine artery resistance and angiogenic imbalance characterized by increased soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased free vascular endothelial growth factor (VEGF) are often associated with placental insufficiency and preeclampsia but not synonymous with hypertension. We hypothesized chronic reductions in utero-placental perfusion (RUPP) for 5 days (d) during either mid- (d12-d17) or late (d14-d19) gestation would have disparate effects on plasma sFlt-1 and VEGF levels and blood pressure. Five days of chronic RUPP was achieved by placement of silver clips on the abdominal aorta and ovarian arteries on either gestational d12 or d14. Arterial pressure was increased (P < 0.05) in RUPP vs. normal pregnant (NP) in both d17 (10%) and d19 (25%) groups, respectively. Circulating free VEGF was decreased (P < 0.05) and sFlt-1:VEGF ratio increased (P < 0.05) after 5 days of RUPP ending on d19 but not d17 compared with NP controls. Angiogenic imbalance, measured by an endothelial tube formation assay, was present in the d19 RUPP but not the d17 RUPP compared with age-matched NP rats. Five days of RUPP from days 14 to 19 decreased fetal and placental weights 10% (P < 0.01) compared with d19 NP controls. After 5 days of RUPP, from days 12 to 17 of pregnancy, fetal weights were 21% lighter (P < 0.01) compared with d17 NP controls, but placental weight was unchanged. These findings suggest that the timing during which placental insufficiency occurs may play an important role in determining the extent of alterations in angiogenic balance, fetal growth restriction, and the severity of placental ischemia-induced hypertension.     

Fetal and maternal endocrine responses to exercise in the pregnant ewe

Maternal and fetal concentrations of plasma insulin, pancreatic glucagon, growth hormone (GH), corticosteroids and enteroglucagon, and of blood glucose and lactate, were measured in well-fed, late pregnant ewes before, during and after walking on a treadmill at 0.7 m.s-1, 10 degrees slope for 60 min. Exercise caused rapid and substantial increases in maternal concentrations of glucose, lactate, pancreatic glucagon and corticosteroids, smaller but significant decreases in levels of GH and enteroglucagon, and no change in insulin. With the exception of GH, concentrations of these maternal hormones had returned to pre-exercise levels within 20 min of stopping exercise. The exercise-induced maternal hyperglycaemia was associated with a proportionately similar, rapid increase in fetal blood glucose; fetal blood lactate and plasma corticosteroids also increased, but at slower rates and other fetal hormone concentrations were unchanged. During recovery there was a rapid increase in fetal insulin levels. The results are discussed in terms of the regulation of exercise-induced changes in maternal energy metabolism, and fetal metabolic and hormonal sensitivity to these changes.     

Oxidative stress and diabetes in pregnant rats

A considerable amount of clinical and experimental evidence now exists suggesting the involvement of free radical-mediated oxidative processes in the pathogenesis of diabetic complications. If the diabetic state is associated with a generalized increase in oxidative stress, it might well be reflected in the alterations in embryonic and fetal development during pregnancy. In the present study, incidence of the malformed fetuses, biochemical parameters and antioxidant system activity of streptozotocin (STZ)-induced diabetic pregnant rats was investigated and the results obtained were compared with those of the control group (non-diabetic). Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. All the females were killed on Day 21 of pregnancy and the fetuses were analyzed. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic dams presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased reduced glutathione (GSH), hepatic glycogen and superoxide dismutase (SOD) determinations. There was an increased incidence of skeletal and visceral malformation in fetuses from diabetic rats. Our findings suggest that oxidative stress occurs in the diabetic pregnant state, which might promote maternal homeostasis alterations. These diabetic complications might be a contributory factor to conceptus damage causing embryonic death (abortion/miscarriage) or the appearance of malformations in the fetuses of diabetic dams. Antioxidant treatment of women with diabetes may be important in future attempts to prevent congenital malformations.     

Impact of a cholesterol enriched diet on maternal and fetal plasma lipids and fetal deposition in pregnant rabbits.

Pregnancy is associated with a hypercholesterolemic and a hyperlipidemic state. The totality of the essential fatty acids and 50% of the lipids needed by the fetus are transferred by the placenta from the maternal circulation. The hypothesis of this study is that an augmentation of the maternal plasmatic cholesterol is modifying the fetal lipids accumulation and development during rabbit pregnancy. To demonstrate the impact of a cholesterol enriched diet on plasma lipids during rabbit's pregnancy and on their fetus, we have established two groups: control and hypercholesterolemic rabbits (fed with a 0.2% cholesterol diet). Blood samples were collected before mating and at each trimester of pregnancy for analysis of lipid fractions and their lipoproteins. Plasma analysis shows that starting the 10th day of pregnancy the concentration of total-cholesterol and lipoproteins decreases for both groups. We have demonstrated that for the hypercholesterolemic group, concentrations of total-cholesterol (631%) and lipoproteins are significantly higher at the end of pregnancy than those for the control group. For both groups, after 20 days of pregnancy, triglycerides metabolism was biphasic showing a significant increase followed by a diminution in their concentration. In both groups, free fatty acids increases significantly at the end of the pregnancy (537.5% for the control group and 462.5% for the hypercholesterolemic group). Furthermore, the offsprings of hypercholesterolemic dams manifest a lower birth weight (15.5%) than those of control group. Our results demonstrate that a cholesterol enriched diet modifies greatly the fetal development and lipid metabolism during rabbit's pregnancy. These modifications could be useful for the understanding of the interaction between diet and fetal development in rabbit and probably during human pregnancy.     

Bioassayable growth hormone release in rats in response to a single bout of treadmill exercise.

Plasma growth hormone (GH) measured by immunoassay [immunoassayable GH (IGH)] and by tibial bioassay [bioassayable GH (BGH)] increases in humans in response to exercise. In rats, however, IGH does not change in response to exercise. The objective of this study was to determine the BGH response to an acute exercise bout in rats. The rats ran on a treadmill at a rate of 27 m/min for 15 min, after which plasma and pituitary hormones, including IGH and BGH, and plasma metabolites were measured. Plasma and pituitary IGH were unchanged from control groups after the acute exercise bout, whereas plasma BGH was increased by 300% and pituitary BGH was decreased by 50%. Plasma thyroxine and corticosterone levels were significantly increased after a single exercise bout, but plasma testosterone, 3,5, 3'-triiodothyronine, glucose, lactate, and triglyceride concentrations were unchanged. Given previous results from in situ nerve stimulation studies (Gosselink KL, Grindeland RE, Roy RR, Zhong H, Bigbee AJ, Grossman EJ, and Edgerton VR. J Appl Physiol 84: 1425-1430, 1998), these in vivo results are consistent with the rapid BGH response during exercise being induced by the activation of muscle afferents.     

Energy sources mobilization during muscular exercise in pregnant rats

The experiments were carried out on three groups of female Wistar rats: nonpregnant rats (NP), rats pregnant for 10 days (P-10) and rats pregnant for 19 days (P-19). The rats were exercised on a treadmill set at 10 degrees incline at a running speed of 1200 m/h. Measurements were made at rest, after 30 min exercise, and after exercise till exhaustion. It was shown that in P-10 group the ability for the exhaustive exercise and metabolism of energy substrates during exercise were similar to those in NP group. The ability for exhaustive exercise of P-19 rats was reduced by 54.6% vs. NP rats. During exercise in P-19 group mobilization of glycogen in skeletal muscles was accelerated, mobilization of liver glycogen was impaired and hypoglycemia developed earlier than in NP group. Plasma FFA level in P-19 group reached a peak already after 30 min of exercise. Plasma triglyceride level was reduced during exercise in NP and P-10 groups but not in P-19 group. The level of triglycerides in skeletal muscle of each group was reduced during exercise but in P-19 group it returned to the resting level after the exhaustive exercise.     

PINA is essential for growth and positively influences NIMA function in Aspergillus nidulans

The phospho-Ser/Thr-directed prolyl-isomerase Pin1 was originally identified in vertebrate systems as a negative regulator of NIMA, a Ser/Thr protein kinase that regulates the G(2)/M transition in Aspergillus nidulans. Here we explore the physiological roles of the Pin1 orthologue, PINA, in A. nidulans and evaluate the relevance of the interaction of PINA with NIMA in this fungus. We find pinA to be an essential gene in A. nidulans. In addition, when PINA levels are reduced 50-fold the cells grow at a reduced rate. Upon germination under conditions that repress PINA expression, the cells are delayed in the interphase activation of NIMX(cdc2), whereas they traverse the other phases of the cell cycle at a similar rate to controls. These results indicate that a marked reduction of PINA results in a lengthening of G(1). Additionally, PINA repression increases the rate at which the cells enter mitosis following release from a hydroxyurea arrest without altering the sensitivity of the fungus to agents that activate the replication or DNA damage checkpoints. In contrast to predictions based on Pin1, the physical interaction between PINA and NIMA is primarily dependent upon the prolylisomerase domain of PINA and the C-terminal 303 amino acids of NIMA. Finally, reduction of PINA levels exacerbates the nimA5 temperature-sensitive mutant, whereas overexpression of PINA decreases the severity of this mutation, results that are consistent with a positive genetic interaction between PINA and NIMA. Thus, although PINA is essential and positively regulates NIMA function, A. nidulans is most sensitive to a reduction in PINA concentration in G(1) rather than in G(2)/M.