MATERNAL UNDERNUTRITION AND RETARDED FETAL DEVELOPMENT IN MERINO SHEEP.
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Cytochrome c oxidase during human fetal development.
Histochemical, biochemical and immunologic analysis of cytochrome c oxidase (COX) in skeletal muscle, heart and kidney during human fetal development was performed. COX histochemical activity was present only in few muscle fibres from the 11th to the 20th week of gestation. At the same developmental stage intrafusal muscle fibres, heart and kidney already showed strong activity. At the 28th week of gestation muscular COX activity was present in about 90% of the fibres. Tissue biochemical analysis confirmed these histochemical findings. Histochemical and biochemical findings compared to the immunocytochemical results and ELISA indicate that COX activity parallels the progressive synthesis of the enzyme in each tissue.
Electron Transport Complex IV↗
Effect of pregnancy and fetal development on sheep liver superoxide dismutase activity.
Liver cytosolic CuZn SOD activity of four-week and 12-week pregnant sheep was twice as high as that of their fetuses and almost equal to that of control, barren ewes. By the 20th week of pregnancy activity had decreased by about 70 per cent in the maternal liver and increased to a value similar to that of the controls in the fetuses. The lysosomal CuZn SOD activity remained almost unchanged during pregnancy both in the maternal and fetal livers. Cytosolic and lysosomal CuZn SOD activities of 20-week pregnant sheep and their fetuses showed a similar electrophoretic pattern and low electrophoretic mobility. Hepatic Mn SOD activity increased sharply during fetal development but remained lower than that in both the control and maternal livers. It is proposed that the changes in CuZn SOD and Mn SOD activities are associated with changes in copper metabolism and oxygen utilisation, respectively. The low electrophoretic mobility of CuZn SOD is assumed to be a species specificity.
Animals↗
Fetal development after transfer is increased by replacing protein with the glycosaminoglycan hyaluronan for mouse embryo culture and transfer.
The effect of macromolecules on mouse embryo development and viability after culture in sequential media was investigated. It was found that high rates of viable blastocysts could be obtained in the absence of any macromolecule. Blastocyst cell numbers were increased when bovine serum albumin was present in the culture medium, although this benefit was not manifest after blastocyst transfer. Rather, the highest rates of implantation and fetal development after blastocyst transfer were observed when hyaluronan was the macromolecule in the culture media. Subsequent analysis revealed that the beneficial effects of hyaluronan were due to its presence in the transfer medium. As the highest cell numbers and hatching rates obtained in this study occurred when both serum albumin and hyaluronan were present in the same medium, it is proposed that embryo culture media should contain both serum albumin and hyaluronan, while the transfer medium need only contain hyaluronan.
Animals↗
Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development.
Tyrosine hydroxylase catalyses the initial, rate-limiting step in the catecholamine biosynthetic pathway. Catecholamines, which include dopamine, noradrenaline, and adrenaline, are important neurotransmitters and hormones that regulate visceral functions, motor coordination and arousal in adults. The gene encoding tyrosine hydroxylase becomes transcriptionally active in developing neuroblasts during mid-gestation of rodent embryos, before the onset of neurotransmission. Here we show that inactivation of both tyrosine hydroxylase alleles results in mid-gestational lethality: about 90% of mutant embryos die between embryonic days 11.5 and 15.5, apparently of cardiovascular failure. Administration of L-DOPA (dihydroxyphenylalanine), the product of the tyrosine hydroxylase reaction, to pregnant females results in complete rescue of mutant mice in utero. Without further treatment, however, they die before weaning. We conclude that catecholamines are essential for mouse fetal development and postnatal survival.
Alleles↗
Leptin and its role in pregnancy and fetal development--an overview.
Leptin is a hormone that is secreted by adipose cells in proportion to adipose mass, and therefore a low leptin level signifies depletion of energy stores. It has been proposed that leptin is one of the signals controlling sexual maturation. For example, humans and rodents lacking leptin fail to undergo complete puberty, while overexpression of leptin in mice causes early puberty. The placenta also produces leptin in human pregnancy, increasing the amount in the maternal circulation. The effects of the increased leptin levels during pregnancy are not clear. In contrast, the mouse placenta does not produce endocrinologically significant amounts of leptin. The mouse placenta does secrete a leptin-binding protein, the production of which correlates with a large increase in maternal leptin levels. The physiology of leptin during pregnancy and fetal development differs significantly between species, and is not well understood in any.
Animals↗
Densities of nitric oxide synthesizing nerves in smooth muscles of human gut during fetal development.
BACKGROUND/PURPOSE: Nitric oxide (NO) plays a role in inhibitory neurotransmission in the sphincteric and nonsphincteric smooth muscles. However, the relative contribution of NO synthesizing innervation to these functionally diverse parts of the gut, particularly during development, is unknown. METHODS: Gastrointestinal sphincters and adjoining nonsphincteric bowel segments were obtained from 14 human fetuses (gestation, 12 to 23 weeks). NO synthesizing nerves were examined by nicotinamide adenine deoxinucleotide phosphate (NADPH) diaphorase histochemistry. The densities of NADPH-positive nerves in the smooth muscles were quantified using a computerized image analyzing system on random sections. RESULTS: The NO synthesizing nerve density in intestinal smooth muscles decreased during fetal development as a result of increased interspacing between myenteric ganglia and a disproportionately larger increase in smooth muscle area than neuronal area. The nerve densities were lower in sphincteric regions than the adjoining nonsphincteric regions at the same gestation. CONCLUSION: These findings may have relevance to the occurrence of congenital dysmotility disorders of the sphincteric regions.
Digestive System↗
Changes in myocardial A1 adenosine receptor and message levels during fetal development and postnatal maturation.
Previously we have shown myocardial adenosine A1 receptors are up-regulated during the newborn period. The timing of the increase or the mechanism of the changes are not known. The purpose of the present study was to (1) determine the time course of increased A1 adenosine receptors during fetal development and (2) determine if A1 adenosine receptor regulation is secondary to changes in A1 receptor mRNA levels. A1 adenosine receptor density was determined in whole hearts from fetal rats at 14 and 19 days' gestation and from newborn and adult rats using standard receptor-binding techniques. A quantitative PCR assay was developed to measure A1 adenosine receptor mRNA using total RNA samples from the above ages. A1 receptor density (fmol receptor/mg protein) increased during late gestation (79 +/- 14 and 122 +/- 7 in 14 and 19 days' gestation respectively) peaked during the newborn period (136 +/- 12) and decreased in the adult rat (36 +/- 5). A1 receptor message levels (fg message/microgram total RNA) changed in parallel to receptor density (7.2 +/ 1.7, 15.6 +/- 1.8, 19.9 +/- 4.3 and 9.9 +/- 1.3 in 14 and 19 days' gestation, newborn and adult respectively). These results provide evidence for transcriptional control of A1 receptor density and the increased receptor density in the newborn heart supports a possible role for the A1 receptor in the transition to the extrauterine circulation.
Animals↗
Morphologic parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates.
BACKGROUND: Many different embryo selection criteria have been used in assisted reproductive technologies (ART), but there are no published prospective studies to ascertain their usefulness in predicting implantation. METHODS: In a prospective trial, 20 early scoring parameters previously reported to influence clinical outcome were collected, but embryos were selected for transfer by current laboratory protocols; day 1 pronuclear (PN) (Z) score combined with day 3 or 5 morphology. Data points for each oocyte/embryo were scored independently and tracked individually. Data were analysed retrospectively for parameters most likely to result in a positive pregnancy test, fetal heartbeat (FHB) and delivery. RESULTS: Results indicated that day 1 PN morphology and nucleolar precursor body (NPB) ratio, day 2 cell number, blastomere symmetry and nucleation and the ability to cleave from day 2 to day 3 were the six most significant factors in fetal development. This outcome was then applied prospectively over 8 months. The implantation rate (IR) and clinical pregnancy rate (CPR) increased in each age group, and the number of embryos used decreased. CONCLUSION: In conclusion, early parameters that include PN morphology, number and ratio of NPBs per nucleus and the day 2 morphology of cleaving embryos are stronger positive predictors of implantation than day 3 morphology or the ability to achieve the blastocyst stage of development. Parameters that were most consistently correlated with no delivery were lack of PN symmetry, day 2 multinucleation and uneven cell size. Day 3 and day 5 parameters were not significant compared with the combination of early parameters.
Adult↗
Gene expression of tyrosine hydroxylase in the developing fetal brain.
Tyrosine hydroxylase, aromatic L-amino-acid decarboxylase, and dopamine beta-hydroxylase activities were studied in the developing fetal rat brain. A delay of 2-3 days between the detection of the tyrosine hydroxylase and the aromatic L-amino-acid decarboxylase and dopamine beta-hydroxylase activities was observed. For this reason, the expression of tyrosine hydroxylase mRNA was studied. Tyrosine hydroxylase mRNA was visualized in the whole brain from 13 days of gestation, but the largest increase of the expression was observed in the hypothalamus. These results are discussed in terms of the relative gene expressions of the three enzymes involved in the biosynthesis of catecholamines and phenolamines in nervous tissues.
Actins↗
Activity of the bifunctional protein 4a-hydroxy-tetrahydropterin dehydratase/DCoH during human fetal development: correlation with dihydropteridine reductase activity and tetrahydrobiopterin levels.
The dehydratase activity of the bifunctional protein, 4a-hydroxy-tetrahydropterin dehydratase/DCoH was measured in liver during early human fetal development to determine whether it appeared in concert with the other components of the phenylalanine hydroxylating system. Catalytic activity of the dehydratase is detectable as early as 6.7 weeks and increases linearly with time, reaching 31% of the adult value by 17.3 weeks of gestational age. Close correlation was found with the development of dihydropteridine reductase, which increased linearly to 37% of the adult value at 17.3 weeks of gestation. From 8-18 weeks of gestation tetrahydrobiopterin in fetal liver was 0.86 microM (33% of adult value). The ratio of 7-biopterin to 6-biopterin was more than 8-fold higher in fetal than in adult liver during this time. The co-development of 4a-hydroxytetrahydropterin dehydratase with dihydropteridine reductase strongly supports a physiologically significant role for the dehydratase in tetrahydrobiopterin regeneration. In addition, the results have lead to a hypothesis for the transient nature of the hyperphenylalaninemia observed in a variant form of PKU in which levels of 7-biopterin are elevated.
Adult↗
Influence of maternal obesity on fetal development in pigs.
Fetuses from linebred lean (L) and linebred obese (O) and reciprocal crossmatings were examined at 110 d of gestation for line, maternal and heterotic effects. There was no significant heterotic effect for any trait measured. A significant maternal effect was observed for adipose tissue lipoprotein lipase (LPL) activity and for serum triglycerides. The enzyme activity and triglycerides concentration were higher in fetuses from O dams than in fetuses from L dams. In a lipid clearance test, no maternal effect was observed for changes in serum concentrations of triglycerides and free fatty acids or in optical density (associated with the disappearance of injected Liposyn). Linebred O fetuses exhibited higher LPL activity in both the biceps femoris muscle and sc adipose tissue compared with linebred L fetuses. The LPL activity of the adipose tissue was higher than that of the skeletal muscle. The percentage of dry matter, percentage of triglycerides and protein/DNA were higher in the muscle of linebred O fetuses than in that of linebred L fetuses. Based on tissue LPL activity and on muscle compositional traits, linebred O fetuses were more mature at 110 d of gestation than were the linebred L fetuses. Maternal obesity had little detectable influence on fetal development of the pig when measured at 110 d of gestation.
Animals↗
Testosterone regulation of sex differences in fetal lung development.
Fetal lung development, in particular surfactant synthesis, exhibits a sexual dimorphism. Dihydrotestosterone (DHT) has been shown to delay fetal pulmonary surfactant production, but the potential role for testosterone is unknown. Both testosterone and DHT are potent masculinizing hormones, yet in some instances, an end organ specificity for DHT is present. We hypothesized that the delay in fetal lung surfactant production is dependent upon DHT such that inhibition of the synthesis of DHT from the precursor hormone testosterone would eliminate the sex difference by allowing the male fetus to produce surfactant at the female level. We tested this hypothesis using 17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5-alpha-androstane-3-one (4-MA), a potent inhibitor of the enzyme 5 alpha-reductase, which converts testosterone into DHT. First, studies were performed in vivo. 4-MA (20 mg/kg/day) or an equivalent volume of vehicle was injected into pregnant rabbits from Day 12 through Day 26 of gestation. On Day 26, the fetuses were delivered, the lungs were lavaged, and fetal sex was noted. Treatment with 4-MA resulted in a lack of any male-female difference in the anogenital distance and no DHT was detected in the serum of any treated fetus. Phosphatidylcholine (PC), saturated phosphatidylcholine (SPC), and sphingomyelin (S) were measured in the lung lavage, and were expressed as the ratios of PC to sphingomyelin (PC:S) and SPC to sphingomyelin (SPC:S). Sex differences in the PC to sphingomyelin ratio of 4-MA-treated fetuses (female PC:S ratio, 1.43 +/- 0.14; male PC:S ratio, 1.00 +/- 0.13 [mean +/- SE]; P = 0.04) and in the SPC:S ratio of the 4-MA-treated group (female SPC:S ratio, 0.68 +/- 0.10; male SPC:S ratio, 0.35 +/- 0.10; P = 0.03) were present after treatment with 4-MA. The effect of testosterone and of 4-MA on fibroblast pneumonocyte factor (FPF) production was studied in vitro. Fetal rat lung fibroblasts were cultured to confluence with either no added androgen, DHT, testosterone, or testosterone plus 4-MA, and conditioned media for FPF were prepared. Conditioned media were added to fetal Type II cell cultures and FPF activity was measured as the degree of stimulation of the incorporation of [3H] choline into SPC. The conversion of radiolabeled testosterone to DHT by the fibroblasts was inhibited by 4-MA (10(-5) M). Conditioned media from untreated female fibroblasts stimulated with cortisol exhibited significant FPF activity ([3H]choline incorporation into SPC, 140 +/- 17% of control).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Effect of different intensities of iron-deficient anemia in pregnant rats on maternal tissue iron and fetal development.
Effect of the different intensities of iron-deficient anemia in pregnant rats on the maternal tissue iron and the fetal development was investigated. The different intensities of iron deficiency were produced by changing period of feeding on the iron depleted diet (0.38 mg/100 g diet) prior to gestation. The anemic rats were divided into three groups with the hemoglobin levels of 12, 10 and 8 g/100 ml on the first day of gestation. Then, rats of each group were fed on the iron adequate and on the depleted diets during gestation. The whole body weights of the three deficient animals were lower than those of the corresponding controls on day-21 of gestation. Food intakes of the three deficient groups tended to be lower than those of corresponding controls. The values of hemoglobin (Hb), hematocrit (Ht) and red blood cells (RBC) decreased with the progress of pregnancy, and the hypochromic anemia was observed in all deficient animals. Iron contents of various tissues and the ratio of ferritin iron to total iron in liver and spleen of each deficient group were also apparently lower than those of corresponding controls. The numbers of placenta of the deficient groups were similar to those of corresponding controls. The litter size of severe anemic-animals was less than those of light and moderate anemic-animals, and the average body weight of fetus in severe anemic-animals was much lower than those of other groups. These results suggested that a higher severity of anemia in the mother at the beginning of pregnancy may result in a more frequent resorption of the fetus but the anemic status did not affect the ability of gestation itself.
Anemia, Hypochromic↗
Fetal development of the human cervical spine and cord.
The growth of the human vertebral canal and the spinal cord during normal fetal development was studied. The results suggest that these two parts of the developing body exhibit a similar developmental pattern. Computer analysis also revealed that the rate of this parallel growth is considerably lower than that of the body as a whole but similar to that reported for the brain. These results are discussed in relation to the pathogenesis of certain neurological diseases.
Cervical Vertebrae↗
Secretion of lung fluid by the developing fetal rat alveolar epithelium in organ culture.
We studied lung explants in submersion organ culture to examine the role of the developing fetal alveolar epithelium in the production of lung fluid. Fourteen-day-gestation fetal rat lungs were grown in a collagen gel matrix supplemented with F-12 media and 10% fetal calf serum. In this model, the lung continues to grow, secrete fluid, and become progressively cystic in morphology. There is gradual thinning of the distal epithelial layer, which is lined by alveolar type II cells and their precursors. After 6 to 8 days in culture, we impaled the cyst walls with a microelectrode and continuously recorded the transepithelial potential (psi t). Stable, baseline transepithelial potentials of -1.1 to -6.2 mV (mean +/- SEM = -3.3 +/- 0.11 mV, lumen negative, n = 34) were measured in bicarbonate-buffered Ringer's solution, suggesting active electrolyte transport. When bumetanide, an inhibitor of chloride secretion in other systems, was added to the bathing solution, psi t decreased from a baseline of -3.5 +/- 0.07 mV (mean +/- SEM) to a value of -2.2 +/- 0.07 mV, suggesting chloride transport contributes to the voltage (n = 18, P less than 0.0005). Isoproterenol hyperpolarized psi t from a baseline of -4.3 +/- 1.0 mV to -6.5 +/- 1.0 mV (n = 7, P less than 0.005). 8-(4-Chlorophenylthio) adenosine 3':5'cyclic monophosphate (CPT-cAMP) plus isobutylmethylxanthine (IBMX) similarly hyperpolarized psi t from a baseline of -4.6 +/- 0.4 mV to -7.3 +/- 0.7 mV (n = 11, P less than 0.005). Addition of bumetanide after stimulation with isoproterenol or CPT-cAMP/IBMX depolarized psi t.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Evaluation of maternal infusion therapy during pregnancy for fetal development.
The aim of this project was to study the possible association between maternal infusion treatments during pregnancy and variables of fetal development as well as the occurrence of congenital abnormalities (CA) in a case-control design. The large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) was evaluated based on the medically recorded infusion treatment during pregnancy. Of 22,843 case pregnant women who had newborns or fetuses with congenital abnormalities, 112 (0.5%), while of 38,151 control pregnant women who had newborn infants without any defects, 262 (0.7%), had infusion treatment during pregnancy. Infusion treatment was more frequent in the control group than in the case group with congenital abnormalities (adjusted POR with 945 95% CI: 0.7, 0.6-0.9) and there was no higher rate of maternal infusion treatments in any congenital abnormality group. Mean gestational age was shorter and mean birth weight was smaller in control newborn infants without CA born to mothers with infusion treatment during pregnancy than in the babies of mothers without infusion treatment. The prevalence of mild intrauterine growth retardation was more frequent in the fetuses of pregnant women with hyperemesis gravidarum treated with infusion. The results of the study suggest that infusion treatment of pregnant women did not associate with a higher risk of congenital abnormalities. In addition, the intravenous infusion of drugs has some, but limited efficacy to prevent the adverse effects of hyperemesis gravidarum and threatened preterm delivery.
Journal Article↗
[The thyroid and fetal development].
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Female↗