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PubMed1985

Fetal lung development: compressibility as a measure of maturity.

Fetal lung maturation involves a number of separate developmental processes. An ultrasonic technique is reported for grading the dynamic behavior of the right middle lobe or lingula in the second or third trimesters on ultrasound (US) study. Fetal lungs are stiff initially. Lung compressibility during diastole is typical after 36 weeks' gestational age, when phospholipid profiles of the amniotic fluid also indicate lung-tissue maturity. Compressibility also occurs earlier in the third trimester and has indicated, in preliminary observations on a small subgroup of infants delivered prematurely, a low risk of subsequent neonatal respiratory distress syndrome. High-speed magnification US study of fetal lung compressibility can be used to evaluate fetal lung development, possibly independently of gestational age and of conventionally measured lecithin/sphingomyelin values in amniotic fluid.

Female↗
PubMed1983

Effects of maternal hyperphenylalaninemia on fetal brain development: a morphological study.

We examined the effects of maternal hyperphenylalaninemia on the morphological development of the fetal and neonatal rat brain. High concentrations of phenylalanine were induced in pregnant rats from embryonic days 14 through 21 by subcutaneous injections of alpha-methylphenylalanine (mPhe) (to inhibit maternal phenylalanine hydroxylase) at a dosage of 30 mg/100 g body weight plus phenylalanine (Phe) supplementation (to raise fetal plasma phenylalanine) at a dosage of 60 mg/100 g body weight two times daily at 12-h intervals. This treatment resulted in a significant hyperphenylalaninemia compared with vehicle-injected, pair-fed control rats. At embryonic day 21, mPhe/Phe-treated embryos displayed a reduced thickness of the cortical plate and marginal zone, a decrease in the size of postmitotic neurons, and an increase in the packing density of cells in the cortical plate. There was an increase in the number of pyknotic cells (cell death) and in the reactive microglia in the mPhe/Phe-treated group. During the postnatal period the differences between mPhe/Phe-treated and control rats became fewer and by postnatal day 7 the morphology of the mPhe/Phe-exposed brains was similar to the controls. These morphologic data, in conjunction with our previous biochemical finding of reduced cerebral DNA, RNA, and protein contents of mPhe/Phe-treated rats, indicate that the induced hyperphenylalaninemia caused a significant delay in the development of the cerebral cortex which was able to undergo recovery during the postnatal period.

Animals↗
PubMed2004

Effects of hormones on fetal lung development.

Endogenous hormones, such as glucocorticoids, play a major role in the development of the fetal lung. Considerable effort has been devoted to defining the underlying physiology and the clinical effects of administration of antenatal glucocorticoids to women who are at risk of premature delivery. Antenatal glucocorticoids have significant therapeutic benefits to the neonate with respect to the respiratory distress syndrome, intraventricular hemorrhage, and mortality. Current controversies relate to the choice of glucocorticoid, optimal dosing regime, number of courses of therapy that should be administered, and, most importantly, potential toxicities.

Clinical Trials as Topic↗
PubMed1996

Expression of GH, TSH beta, LH beta and FSH beta genes during fetal pituitary development in the pig.

The development of the anterior pituitary gland involves the proliferation and differentiation of ectodermal cells in Rathke's pouch to generate distinct cell types, each of which produces its corresponding trophic hormone. Studying pituitary development will therefore reveal novel aspects of organogenesis. In the present study, we examined by in situ hybridization the expression of genes for anterior pituitary hormones during development of the fetal pig pituitary. We found that the beta-subunit gene of thyroid-stimulating hormone (TSH beta) was first expressed at E40, (E = day of embryonal/fetal life), growth hormone (GH) mRNA appeared between E40 and E50, and the gonadotrophin genes (LH beta and FSH beta) were expressed at E50. The transcripts for TSH beta, LH beta and FSH beta were abundantly expressed at about E80, while GH mRNA continued to be richly expressed until after birth. The GH gene was first expressed in the mantle layer of the anterior lobe, while the TSH beta and gonadotrophin (LH beta and FSH beta) mRNAs were found in the central and the basal regions of the anterior lobe, respectively. All of these mRNAs (GH, TSH beta, LH beta, and FSH beta) remained concentrated until the end of gestation in the area where they first appeared. The distinctive pattern of developmental expression of these hormone genes in the fetal pig anterior pituitary makes this tissue an excellent system in which to study tissue-specific gene activation and regulation.

Animals↗
PubMed1983

Fibronectin distribution during the development of fetal rat skin.

Fibronectin distribution during fetal rat skin development has been studied immunocytochemically at the light and electron microscope level from 16 days of gestation to birth. The dermal-epidermal junction, the dermis, and connective tissue around developing muscle were shown by light microscopy to be heavily stained throughout this period. The development of hair follicles from about 18 days onward was not associated with any consistent change in fibronectin distribution. The heavy staining of the upper dermis was associated with a high density of mesenchymal cells, and immunoelectron microscopy revealed fibronectin on the surface of many of these cells and in association with the surrounding fine collagen fibrils. At the dermal-epidermal junction, both follicular and interfollicular, fibronectin was localized mainly in the plasma membrane and lamina lucida regions of the basement membrane, and there was also staining associated with the underlying fine collagen fibrils. These observations are further evidence for the proposed role of fibronectin as a mediator of the cell-matrix interactions which are of importance for tissue development and maintenance.

Animals↗
PubMed1983

Progestin receptors in female rat brain and hypophysis in the development from fetal to postnatal stages.

The fetal and postnatal development of the progestin receptors in the intact female rat brain was investigated by means of the in vitro cytosol binding and the nuclear exchange assay using 3H-R5020 ([17 alpha-methyl-3H] 17 alpha-,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione). A large 7S peak of progestin binding in the cerebral cortical cytosols was observed at days 7-14 with less evident binding in the hypothalamus-preoptic area (HPOA). The cortical cytosol receptors, first detectable at day 0, rapidly increased at days 1-7, reaching a maximum at day 10, then gradually declined thereafter. The receptors in the HPOA and other brain areas appeared at day 1, increased during the first week, then remained constant at days 10-28. Hypophysial cytosol receptors, first detectable at day 10, increased at day 28. Nuclear progestin binding was low in the HPOA and cortex of the neonates at days 1-3. Interestingly, despite the low level of serum progesterone, the cortical nuclear binding suddenly increased at days 7-10, then remained high at days 14-21. A similar, though less pronounced, pattern was seen in the HPOA. Diethylstilbestrol injection caused an increase in the cytosol binding capacities in the HPOA, but did not in the cortex. These results suggest the appearance of the brain progestin receptor system immediately after birth, and differential patterns of their postnatal development in the intact female rat. The onset of increased nuclear translocation of endogenous progestin-receptor complex may occur in the cortex, and possibly HPOA, at around days 7-10. Progestin receptors in the postnatal rat HPOA are estrogen inducible, but not in the cortex.

Animals↗
PubMed2002

Maternal stress and affect influence fetal neurobehavioral development.

The authors investigated the association between maternal psychological and fetal neurobehavioral functioning. Data were provided by 52 maternal-fetal pairs at 24, 30, and 36 weeks gestation. The relations between maternal measures and fetal heart rate, variability, and motor activity were statistically modeled. Fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more frequent pregnancy-specific hassles were more active across gestation. Fetuses of women who perceived their pregnancy to be more intensely and frequently uplifting and had positive emotional valence toward pregnancy were less active. Associations with fetal heart-rate measures were detected at 36 weeks gestation. These data provide evidence for proximal effects of maternal psychological functioning on fetal neurobehavior.

Adult↗
PubMed1999

Impaired fetal thymocyte development after efficient adenovirus-mediated inhibition of NF-kappa B activation.

We introduce a new experimental system combining adenovirus-mediated gene transfer and fetal thymic organ culture (FTOC). This system allowed us to efficiently express in developing thymocytes a mutant form of the NF-kappa B inhibitor I kappa B alpha (mut-I kappa B) and to study the maturation defects occurring when NF-kappa B activation is inhibited during fetal development. Fetal thymocytes infected with adenovirus containing mut-I kappa B were found to develop normally until the CD44-CD25+, CD4-CD8- double-negative stage, while production of more mature double-positive and single-positive populations was strongly decreased. Proliferation, as measured by the percentage of cells in cycle appeared normal, as did rearrangement and expression of the TCR beta-chain. However, apoptosis was much higher in FTOC infected with adenovirus containing mut-I kappa B than in FTOC infected with a control virus. Taken together, these results suggest that NF-kappa B plays a crucial role in ensuring the differentiation and survival of thymocytes in the early stages of their development.

Adenoviridae↗
PubMed1986

Effect of intrauterine positions on fetal brain development in the rat.

The effect of the position on the horn on fetal brain development was studied in 2276 rats (248 litters), by assessing the intrauterine location of those fetuses which had the highest values ('maximal fetuses') of the following parameters: body weight, brain weight, brain DNA (cell number), brain protein and the ratios brain weight/body weight and brain protein/brain DNA. The fetuses were at term (21 days) or at 16-18 days postcoitum. The total numbers of animals in the right and in the left uterine horn were essentially the same: 4.64 and 4.54, respectively. For each parameter, the locations of maximal fetuses were, on the average, symmetrical with respect to the center of each horn. The distributions of maximal fetuses along each horn followed specific patterns, which were different for each horn but showed similar locations of peaks and depressions for various parameters. However, the differences between the peaks and depressions were not statistically significant. It is concluded that both horns are equipotent, and all the positions on the horn are also essentially equipotent for production of animals maximal with respect to parameters studied. This also suggests that occasional cases of outstanding high fetal brain development occur from causes other than a favorable position on the uterine horn.

Animals↗
PubMedDate not supplied

The effect of maternal and fetal thyroidectomy on fetal brain development in the sheep.

The combination of maternal and fetal thyroidectomy was found to have a significant influence on brain development in the fetal sheep at 140 days. There was reduced body weight (36%), brain weight (23%), DNA (26%) and protein (34%) content in five fetuses of ewes, subjected to thyroidectomy six weeks before mating and fetal thyroidectomy at 98 days gestation, compared with six sham operated controls. Cholesterol content was also reduced (36%) and water content increased (2.4%). The cerebellum was most severely affected and showed histologically an increased cell density associated with a significant reduction in the ratio of the molecular to granular cell layer area. The cell density was also significantly increased in the CA1 region of the hippocampus, but not in the CA4 region. It was also increased in the parietal layer of the cerebral cortex but not in the motor region. There was a significant reduction in the weight of heart (28.6%) and lungs (33.4%), while the kidneys and pituitary were enlarged (20.5% and 48.5% respectively) as a result of double thyroidectomy. The combined thyroidectomy was similar to iodine deficiency in its effect on fetal brain development, indicating that it is probable that iodine deficiency has its effects in the sheep by a combination of maternal and fetal hypothyroidism.

Animals↗
PubMed1998

Distribution of integrins during human fetal lung development.

Interactions between epithelial cells and the extracellular matrix through integrins play a key role in the development of the lung by modulating branching morphogenesis, epithelial cell polarization, and differentiation. To determine the role of integrins during the different stages of lung development, we investigated the distribution of eight integrin subunits in the trachea and lung from human fetuses. In distal airways, during the early pseudoglandular stage of development, the alpha2-, alpha5-, alpha6-, alphav-, and beta1-subunits were detected in all epithelial cell plasma membranes, and polarized but undifferentiated tracheal epithelial cells expressed alpha3-, alpha6-, and beta1-subunits in the plasma membrane of the cells facing the basement membrane. The alpha6- and beta4-chains were detected along the basal plasma membrane of the basal cells in differentiated tracheal epithelia. The alpha4-subunit was detected in all respiratory cells throughout fetal development. In the submucosal glands, myoepithelial cells expressed the integrin subunits found in the undifferentiated cells of the developing airways, whereas the secretory cells expressed only alpha2-, alpha3-, alpha4-, alpha6-, and beta1-subunits. These results demonstrate differential expression of integrins during lung development and suggest that integrins may play multiple roles in organogenesis and maturation of respiratory surface epithelium and glands.

Antigens, CD↗
PubMed1986

Trophic effect of amniotic fluid on fetal gastrointestinal development.

To determine if amniotic fluid or its constituent trophic factors influence fetal gastrointestinal tract development we developed models of fetal esophageal ligation to prevent swallowing of amniotic fluid and fetal esophageal cannulation with infusion of various substances to mimic fetal swallowing. A total of 43 fetuses was studied. Esophageal ligation resulted in a 32% reduction in gastric weight and a 40% reduction in serum gastrin level, compared to unoperated controls, whereas intestinal and liver weights were unchanged. Gastric acid concentration averaged 43.4 +/- 7.7 mumole/ml in control fetuses, but only 0.5 +/- 0.5 mumole/ml following esophageal ligation. Infusion of Ringer's lactate solution intragastrically did not prevent the changes in gut development seen after esophageal ligation. In contrast, infusion of bovine amniotic fluid resulted in relatively normal gut development, with a gastric acid concentration of 28.5 +/- 6.9 mumole/ml and liver and gastric weights and serum gastrin levels no different from control. Epidermal growth factor had a potent trophic effect on both somatic and gastrointestinal fetal growth and resulted in a mean gastric acid concentration of 35.2 +/- 6.6 mumole/ml. In contrast, pentagastrin, although restoring gastric weight to control values, had no effect on gastric acid secretion, with a mean of 0.1 +/- 0.1 mumole/ml. We conclude that fetal swallowing of amniotic fluid is essential in fetal gastrointestinal development, possibly via luminal trophic actions of peptides such as epidermal growth factor and gastrin.

Amniotic Fluid↗
PubMed2004

Number of conceptuses in utero affects porcine fetal muscle development.

Unmodified, third parity, control sows (CTR; n = 30) or sows subjected to unilateral oviduct ligation before breeding (LIG; n = 30), were slaughtered at either day 30 or day 90 of gestation and used to determine the effects of numbers of conceptuses in utero on prenatal, and particularly muscle fibre, development. Ovulation rate, number of conceptuses in utero, placental and fetal size, and (day 90 sows) fetal organ and semitendinosus muscle development were recorded. Tubal ligation reduced (P < 0.05) the number of viable embryos at day 30 and fetuses at day 90. Placental weight at day 30 and day 90, and fetal weight at day 90, were lower (P < 0.05) in CTR sows. All body organs except the brain were lighter, and the brain:liver weight ratio was higher in CTR fetuses (P < 0.05), indicative of brain sparing and intrauterine growth restriction in fetuses from CTR sows. Muscle weight, muscle cross-sectional area and the total number of secondary fibres were also lower (P < 0.05) in CTR fetuses. The number of primary fibres, the secondary:primary muscle fibre ratio, and the distribution of myosin heavy chain-Ibeta, -IIa, fetal and embryonic isoforms did not differ between groups. Thus, even the relatively modest uterine crowding occurring naturally in CTR sows negatively affected placental and fetal development and the number of secondary muscle fibres. Consequences of more extreme crowding in utero on fetal and postnatal development, resulting from changing patterns of early embryonic survival, merit further investigation.

Animals↗
PubMed1995

The effect of low amniotic pressure without oligohydramnios on fetal lung development in a rabbit model.

OBJECTIVE: Our purpose was to examine fetal lung development in reduced intraamniotic pressure without amniotic fluid loss. STUDY DESIGN: A circular portion of uterine wall measuring 1 cm in diameter was excised while the chorionic and amniotic membranes were left intact at the twenty-third day of gestation in New Zealand White rabbits. The chorionic and amniotic membranes herniated spontaneously through the defect. RESULTS: Amniotic pressure was significantly reduced after herniation. Lung weight/body weight ratios at term were significantly reduced in experimental fetuses compared with controls. Residual amniotic fluid volumes at term did not differ. Histopathologic examination of lung specimens showed that fetal lungs had not matured in the experimental group as fully as in the control group. CONCLUSION: This experimental study demonstrated that low amniotic pressure impaired fetal lung development, even without oligohydramnios.

Amnion↗
PubMed1996

Development of fetal movement--fetal heart rate coupling from 20 weeks through term.

This study documents the development of fetal heart rate (FHR) change in response to fetal movement (FM) in healthy fetuses from 20 weeks' gestational age through term. Thirty-one fetuses received 50 min of Doppler-based monitoring at 20, 24, 28, 32, 36 and 38-39 weeks. FHR and FM were continuously digitized. A coupling index was computed as the percentage of FMs associated with increases in FHR of 5 beats/min or more within -5 or +15 s of movement onset. The latency between FM onset and FHR change was also computed, as were the amplitude and duration of all movements. FM and FHR became more integrated with advancing gestation. Coupling increased and the latency between FM and FHR changes decreased. Maternal age, blood pressure and fetal sex did not affect FM-FHR coupling, but fetuses of women who reported greater stress in their daily lives and had faster heart rates displayed reduced coupling. These data suggest that the development of FM-FHR coupling reflects the development of the central nervous system during gestation, and that development may be affected by maternal factors.

Adult↗
PubMed1986

Effect of induced oligohydramnios on fetal lung development.

To investigate the impact of oligohydramnios on fetal growth, development, and lung function, amniotic fluid was shunted from alternate gestational sacs into the maternal peritoneal cavity at 23 days' gestation in the fetal rabbit. Uninstrumented fetuses served as controls. Oligohydramnios was confirmed at the time of planned cesarean delivery on either day 26 or 28. Fetuses subjected to prolonged oligohydramnios had significantly decreased body weight at 26 (p = 0.002) and 28 days (p = 0.007). Similarly, lung weight was decreased at 26 (p = 0.02) and 28 days (p = 0.005). There was a trend toward decreased maximum lung volume for instrumented fetuses at 28 days (p = 0.07). Deflation limbs of the pressure-volume curves revealed significantly increased air trapping for instrumented fetuses at 28 days. These studies suggest not only a detrimental effect of oligohydramnios on fetal body and lung weight but also a beneficial effect of premature rupture of membranes on fetal lung function. Analysis of phospholipid and histologic changes is currently under way.

Amniotic Fluid↗