Influence of maternal metabolism and parental genetics on fetal maldevelopment in diabetic rat pregnancy

The purpose of this study was to investigate the influence of parental transgenerational genetics and maternal metabolic state on fetal maldevelopment in diabetic rat pregnancy. Rats from an inbred malformation-resistant (W) strain, and an inbred malformation-prone (L) strain, were cross-mated to produce two different F(1) hybrids, WL and LW. Normal (N) and manifestly diabetic (MD) WL and LW females were mated with normal males of the same F(1) generation to obtain WLWL and LWLW F(2) hybrids. Maternal diabetes increased malformation and resorption rates in both F(2) generations. MD-WLWL offspring had higher resorption rate but similar malformation rate compared with the MD-LWLW offspring. Malformed MD-WLWL offspring presented with 100% agnathia/micrognathia, whereas malformed MD-LWL offspring had 60% agnathia/micrognathia and 40% cleft lip and palate. The MD-WL dams showed increased β-hydroxybutyrate levels and alterations in concentrations of several amino acids (taurine, asparagine, citrulline, cystine, glutamic acid, leucine, tyrosine, and tryptophan) compared with MD-LW dams. Fetal glyceraldehyde-3-phosphate dehydrogenase (Gapdh) activity and gene expression were more altered in MD-WLWL than MD-LWLW. Fetal gene expression of reactive oxygen species (ROS) scavenger enzymes was diminished in MD-WLWL compared with MD-LWLW. Glial cell line-derived neurotrophic factor and Ret proto-oncogene gene expression was decreased in both MD-WLWL and MD-LWLW fetuses, whereas increased bone morphogenetic protein 4 and decreased Sonic hedgehog homolog expression was found only in MD-LWLW fetuses. Despite identical autosomal genotypes, the WL and LW dams gave birth to offspring with markedly different malformation patterns. Together with fetal differences in enzymatic activity and expression of Gapdh, ROS scavengers, and developmental genes, these results may suggest a teratological mechanism in diabetic pregnancy influenced by maternal metabolism and parental strain epigenetics.     

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.     

Effect of maternal exercise on fetal liver glycogen late in gestation in the rat

To determine the effect of maternal exercise on fetal liver glycogen content, fed and fasted rats that were pregnant for 20.5 or 21.5 days were run on a rodent treadmill for 60 min at 12 m/min with a 0% grade or 16 m/min up a 10% grade. The rats were anesthetized by intravenous injection of pentobarbital sodium, and fetal and maternal liver and plasma samples were collected and frozen. Fetal liver glycogenolysis did not occur as a result of maternal exercise. Fetal blood levels of lactate increased 22-60%, but glucose, plasma glucagon, and insulin were unchanged during maternal exercise. Maternal liver glycogen decreased as a result of exercise in all groups of rats except the fasted 20.5-day-pregnant group. Plasma free fatty acids increased in all groups and blood lactate increased in fed (20.5 days) and fasted (21.5 days) pregnant rats. Maternal glucose, glucagon, and insulin values remained constant during exercise. The fetus appears to be well-protected from metabolic stress during moderate-intensity maternal exercise.     

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.     

The influence of parity and maternal preimmunization on fetal survival in mice

It is known that as parity increases, cell-mediated immunity to paternal antigens increases in mice. The article reports an experiment designed to compare the results of normal parity with artificial immunization simulating maternal sensitization to paternal antigens in mice. Virgin females were immunized at weekly intervals by intraperitoneal injections of 50 mcl of heparinized blood from males with whom they would eventually be mated. The immunized virgins and multiparous females were mated for 4 to 6 weeks after their last injection or litter. The total and live litter size increased with immunization; the total size with natural parity also increased though the live litter size slightly decreased with parity. The mean fetal death rate was relatively the same for both groups. Fetal weight increased with parity but not change was observed in placental weight. Both fetal and placental weight did not change with immunization. There was no increase in the expected number of male fetuses. The increased litter size in the immunized group may be due to increased ovulation rates.     

Effect of exercise during pregnancy, graded as a percentage of aerobic capacity: maternal and fetal responses of the rat.

1. A number of variables were studied in pregnant rats that underwent strenuous exercise during pregnancy. They were: total weight gain, daily weight gain, length of pregnancy, number of offspring. Also the weight, the heart weight and fibre/capillary ratio of the newborn male rats and their VO2 max at 90 days were measured. 2. The exercise was graded in accordance to previous aerobic capacity as determined by VO2 max with relative loads of 60% (E60), 70% (E70), 80% (E80) and 90% (E90) of VO2 max being applied to the various groups (N = 6 per group). 3. The total weight gain and daily weight gain was significantly less in the E70, E80 and E90 groups. Weight gain in the anabolic phase (0-14d) was not different, but during the first week the weight gain in the E90 group was significantly less than control group. In the catabolic phase the observations were similar the first week of the anabolic phase. 4. Length of pregnancy, heart weight offspring and VO2 max of 90-day-old male rats were not significantly different. The number of offspring of the E90 group was significantly smaller than the control, E60 and E70 groups. 5. The offspring body weight was less in the E70, E80 and E90 groups than control group and was significantly less in the E90 group compared to the E60 and E70 groups. 6. The fibre/capillary ratio of the offspring was different in the E90 group compared to the control group. 7. These results suggest that the effect of exercise depends on the relative work load applied to the mother and these effects are particularly marked at high work loads.     

A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy.

Several viral infections have been reported to result in more severe disease in pregnant than non-pregnant women, but the relative risks have not been well characterised. This has now been done for Lassa fever in a prospective study of 68 pregnant and 79 non-pregnant women who were admitted to hospital in Sierra Leone with confirmed Lassa fever. Lassa fever was the main cause of maternal mortality in the hospital, accounting for 25% of maternal deaths. Twelve of 40 patients in the third trimester died, compared with two of 28 in the first two trimesters and 10 of 79 non-pregnant women. The odds ratio for death in the third trimester compared with the first two trimesters was 5.57 (95% confidence intervals 1.02 to 30.26). The condition of the mother improved rapidly after evacuation of the uterus, whether by spontaneous abortion, evacuation of retained products of conception, or normal delivery; 10 of 26 women without uterine evacuation died, but only four of 39 women with evacuation died (p = 0.0016). The odds ratio for death with pregnancy intact was 5.47 (95% confidence interval 1.35 to 22.16). Fetal and neonatal loss was 87%. The risk of death from Lassa fever in the third trimester is significantly higher than that in the first two trimesters and higher than that for non-pregnant women, but evacuation of the uterus can significantly improve the mother''s chance of survival.     

Effects of the diet consumed during the pregnancy on the lipids content in maternal and fetal rat lungs.

This study was designed to determine if the quantity of lipids in the diet fed to pregnant rats would affect the deposition of fat in the fetal lung. Wistar rats were fed with two different diets during pregnancy: Standard Diet (StD; 4.000 cal/g) and High Fat Carbohydrate Free Diet (HFCFD; 6.000 cal/g). The rats consumed daily the same amount of calories from these different diets. The concentrations of triglycerides (TG), phospholipids (PL), total, esterified and free cholesterol (TC, EC and FC, respectively) were determined in serum and lung from pregnant rats as well as from their 19 day old fetuses. In the serum of rats fed with HFCFD, the cholesterol concentration increased in relation to that of rats fed with StD. In pregnant rat lung, the PL concentrations decreased and the TC, EC and FC concentrations increased with HFCFD in relation to StD. The triglycerides were not modified in any case. The lipidic composition of the sera and fetal lung were not changed by the two diets consumed by pregnant rats. This may be a biological protective mechanism to assure an adequate synthesis of alveolar surfactant.     

Effects of environmental stress or ACTH treatment during pregnancy on maternal and fetal plasma androstenedione in the rat

Prenatal stress applied during the last trimester of pregnancy has been shown to alter fetal development and influence adult sexual behavior. Since androstenedione (Δ⁴) has the potential to participate in differentiation processes, this study was designed to assess the effect of prenatal stress on maternal and fetal Δ⁴ titers. Restraint/illumination/heat (environmental stress) or ACTH injections were used to stress pregnant rat dams beginning on Day 14 of pregnancy. Blood samples and organ weights were obtained from nonpregnant animals, pregnant rats on Days 5, 10, 15, 18, and 20 of pregnancy, and fetuses on Days 18 and 20 of gestation. Maternal and male and female fetal Δ⁴ titers were determined by radioimmunoassay. ACTH and environmental stress significantly reduced fetal body weight and male anogenital distance. Environmental stress also significantly reduced the size of 20-day fetal adrenals and testes. Each treatment caused significant short-term (1 hr after treatment) and long-term (16 hr after treatment) elevation of maternal plasma Δ⁴ on Days 15 and 18 of gestation, but only short-term elevation of Δ⁴ titers on Day 20. ACTH treatment did not cause long-term elevation of fetal Δ⁴ although both ACTH treatment and environmental stress generated a significant short-term increase in fetal Δ⁴ titers. Environmental stress produced long-term elevation of fetal Δ⁴ in 18-day fetuses of both sexes and in 20-day female fetuses. It is concluded that maternal stress and exogenous ACTH significantly elevate maternal and fetal Δ⁴ titers during the prenatal period postulated to be critical in sexual differentiation of the rat brain.     

The influence of fetal number on maternal concentrations of progesterone and testosterone in the mouse

Mice selected for large litters were used to study the relationship between fetal number and maternal progesterone and testosterone concentration. Experimental adjustment of conceptus number demonstrated that the presence of one fetus was sufficient to elevate maternal progesterone concentration above that found in females from which all conceptuses were removed. When one of more fetuses occupied the uterus, maternal progesterone concentration did not increase with increasing conceptus number. In contrast, maternal testosterone concentration was positively correlated with the number of fetal-placental units.     

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.     

Effect of moderate exercise on rat T-cells.

The aim of this study was a detailed examination of the effects of moderate exercise on T-cells in adult male Wistar rats. The T-cell populations were compared in sedentary rats (C, n = 5) and in rats trained for 4 weeks on a treadmill (30-60 min.day-1, 6 days.week-1, 20-30 m.min-1) and sacrificed at rest (T-rest, n = 5). In the T-rest rats, there were higher percentages of CD4+CD8-, CD4-CD8+ and CD4-CD8- thymocytes (P < 0.05, P < 0.05 and P < 0.01 respectively) and of CD4-CD8+ splenocytes (P < 0.01), and a lower percentage of CD4-CD8+ cells in the lymph nodes (P < 0.01). Compared with T-rest or C rats, trained rats (n = 5) or untrained rats (n = 5) sacrificed immediately after a running session (60 min, 30 m.min-1) had a higher percentage of mononucleated cells CD4+CD8- in the blood (P < 0.05 and P < 0.01). Lastly, compared with C rats, rats (n = 5) sacrificed immediately after their 5th day of training (30-60 min.day-1) presented a higher total splenocyte population (P < 0.05) and greater in vitro production of T-cell growth factor (interleukin 2 + Interleukin 4) by splenocytes in response to a mitogen (P < 0.01). These results would indicate that moderate endurance training modifies the cellular composition of lymphoid organs, without impairing the in vitro functions of T-cells.     

Effects of insulin and maternal diabetes on fetal lipogenesis in the rat

Offspring of diabetic mothers have been investigated with regard to fetal hepatic and brown adipose tissue lipogenesis in the rat. Results, which cannot be explained by existing theory, are obtained from offspring of subdiabetic mothers and manifest diabetic mothers. In re-evaluating the effect of exogenous insulin on perinatal lipogenesis, we find important differences in hormone sensitivity between liver and brown adipose tissue.     

The influence of the rat maternal environment on the behavior of offspring

In Wistar's rats, the postnatal influence of maternal behaviour on the motor and emotional state and the anxiety level of the posterity born from the intact rat-mothers-ambidexter but reared by the intact mothers-ambidexter with the motor deficit, were investigated. From the first day of life, the rat-mothers with the removed part of the sense-motor cortex (right or left) nursed and reared the litter. It was discovered that the reduction of motor activity and increase of negative emotional responses occurred in experimental litter at the age of 1 month as compared with the control group (intact litter reared by the ersatz healthy rat-mothers). In the test of elevated cruciform maze, a high level of anxiety was discovered. The experimental posterity showed an emotional tension as the dominant state. Left-side lesion of the sense-motor cortex of the ersatz mother resulted in a rougher disorder in the emotional state and movement than after right-side lesion.     

Relationships between some maternal factors and pregnancy outcome

This study, carried out on mother-infant pairs in obstetric hospitals in Istanbul, was designed to investigate the impact of some maternal parameters on pregnancy outcome as well as to provide information on birth weight, and incidence of low birth weight, preterm birth, and small for gestational age birth. Low birth weight, preterm birth, and fetal malnutrition are among major risk factors influencing perinatal, neonatal, and postneonatal mortality and morbidity. Reported values for prepregnancy body weight and postpartum measurements of stature, weight, mid-upper arm circumference showed that the women in this series did not have caloric undernutrition, while nearly 9% were of low stature. Maternal stature, postpartum body weight, and postpartum weight and height values were found to be important determinants of birth weight. The frequency of preterm births in this series corresponds fairly well with that found in another group of Turkish mother-infant pairs in which gestational age was determined by Dubowitz scoring. In agreement with many previous studies, maternal stature and body weight stood out as important influences on the outcome of pregnancy in this series. Overall, the nutritional state of the mother prior to pregnancy is the most important determinant of birth weight.