Lethal Fetal Skeletal Dysplasia Determined by Fetal Lung Weight

Isoxsuprine, a beta-sympathomimetic agent used clinically to delay premature parturition and to possibly accelerate fetal lung maturation, was administered to pregnant rats at 48 and 24 h prior to delivery. Newborn rats were placed in 96-98% O2 (or room air) to determine if the prenatal isoxsuprine treatment compromised their tolerance to prolonged hyperoxic exposure. (Exogenous catecholamines are known to exacerbate O2 toxicity in adult animals). Survival of the isoxsuprine-treated pups in O2 (52%) was no different than for control neonates exposed to hyperoxia for 7 days (57%) (P = 0.22). Body weight, lung weight, lung protein, and DNA content of the newborns were also not altered by the prenatal isoxsuprine treatment. Lung antioxidant enzyme activities for superoxide dismutase, catalase, and glutathione peroxidase were the same at birth in the isoxsuprine-treated and control rat pups, and the enzyme activities increased in response to hyperoxic exposure in each group to an equivalent degree. Thus, in utero treatment with isoxsuprine had no apparent adverse effect on newborn rats exposed to a prolonged O2 challenge.

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RADIOLOGIC DEMONSTRATION OF POSTNATAL LIQUID IN THE LUNGS OF NEWBORN LAMBS

PEDIATRICS ◽

10.1542/peds.46.2.252 ◽

1970 ◽

Vol 46 (2) ◽

pp. 252-258

Author(s):

Barry D. Fletcher ◽

Barry F. Sachs ◽

Robert V. Kotas

Keyword(s):

Body Weight ◽

Caesarean Section ◽

Fetal Lung ◽

Lung Compliance ◽

Pleural Effusions ◽

Interstitial Edema ◽

Lung Weight ◽

Lung Aeration ◽

Lung Liquid ◽

Radiologic Evidence

The liquid which occupies the potential air spaces of the fetal lung is, at birth, displaced by air and removed by the pulmonary blood and lymphatic circulations. Delayed resorption of this liquid from the interstitial spaces may be associated with decreased lung compliance and be the cause of the syndrome "transient tachypnea of the newborn." Chest roentgenograms of these infants have shown the presence of alveolar and interstitial edema and pleural effusions which cleared during the first few days of life. We chose to test the possibility that a delay in clearance of lung liquid might occur and be associated with tachypnea and radiologic evidence of pulmonary edema in newborn lambs. Serial chest radiographs were obtained in 18 newborn lambs delivered at term by Caesarean section. The radiographs demonstrated the presence of lung liquid which gradually cleared in an average time of 2 hours following onset of breathing. Lung weight—body weight ratios obtained following sacrifice at various stages of clearing—decreased as pulmonary aeration increased. Microscopic examination of the lungs showed no evidence of inflammatory exudate or squamous debris but distension of perivascular tissues with liquid was demonstrated. An association between increasing lung aeration and decreasing respiratory rates was found.

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Influence of growth hormone on the lung growth response to tracheal obstruction in fetal sheep

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2000.278.3.l453 ◽

2000 ◽

Vol 278 (3) ◽

pp. L453-L459 ◽

Cited By ~ 6

Author(s):

L. Nardo ◽

I. R. Young ◽

S. B. Hooper

Keyword(s):

Growth Hormone ◽

Dna Content ◽

Fetal Lung ◽

Control Group ◽

Lung Growth ◽

Lung Weight ◽

Fetal Sheep ◽

Tracheal Obstruction ◽

Lung Expansion ◽

Lung Liquid

Obstructing the fetal trachea is a potent stimulus for fetal lung growth, but little is known about the factors that regulate this process. Our aim was to determine the role of growth hormone (GH) in regulating the increase in lung growth induced by obstruction of the trachea in fetal sheep. Twenty chronically catheterized fetal sheep, nine of which were hypophysectomized, were divided into four experimental groups: 1) control group ( n = 4), 2) a group in which the fetal trachea was obstructed for 3 days (3-day obstructed; n = 6), 3) a 3-day obstructed group in which the pituitary was removed [hypophysectomized (HX)] and the fetus was given maintenance infusions of ACTH, thyroxine, and human GH (hGH; HX hGH 3-day obstructed; n = 5), and 4) a HX 3-day obstructed group in which the fetus was given maintenance infusions of ACTH and thyroxine ( n = 5). Tracheal obstruction significantly increased fetal lung liquid volumes from 37.2 ± 3.2 ml/kg in control fetuses to 75.6 ± 9.0 ml/kg in 3-day obstructed fetuses, and the presence or absence of GH did not affect this increase. Similarly, the presence or absence of GH did not affect the increase in lung weight or protein content induced by 3 days of tracheal obstruction. However, in the absence of GH, 3 days of tracheal obstruction failed to increase total lung DNA content above unobstructed control values (107.9 ± 5.3 and 94.1 ± 7.0 mg/kg for control and HX 3-day obstructed groups, respectively). In contrast, 3 days of tracheal obstruction increased total lung DNA content to a similar extent in fetuses with an intact pituitary and HX fetuses that received GH replacement (126.0 ± 4.4 and 126.7 ± 4.0 mg/kg for 3-day obstructed and HX hGH 3-day obstructed groups, respectively). These data indicate that the absence of GH either abolishes or delays the acceleration in cell division caused by an increase in fetal lung expansion.

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Intrauterine Gardnerella vaginalis Infection Results in Fetal Growth Restriction and Alveolar Septal Hypertrophy in a Rabbit Model

Frontiers in Pediatrics ◽

10.3389/fped.2020.593802 ◽

2021 ◽

Vol 8 ◽

Author(s):

Fook-Choe Cheah ◽

Chee Hoe Lai ◽

Geok Chin Tan ◽

Anushia Swaminathan ◽

Kon Ken Wong ◽

...

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Ureaplasma Urealyticum ◽

Rabbit Model ◽

Fetal Lung ◽

Growth Restriction ◽

Gardnerella Vaginalis ◽

Control Group ◽

Lung Weight ◽

Septal Hypertrophy

Background:Gardnerella vaginalis (GV) is most frequently associated with bacterial vaginosis and is the second most common etiology causing intrauterine infection after Ureaplasma urealyticum. Intrauterine GV infection adversely affects pregnancy outcomes, resulting in preterm birth, fetal growth restriction, and neonatal pneumonia. The knowledge of how GV exerts its effects is limited. We developed an in vivo animal model to study its effects on fetal development.Materials and Methods: A survival mini-laparotomy was conducted on New Zealand rabbits on gestational day 21 (28 weeks of human pregnancy). In each dam, fetuses in the right uterine horn received intra-amniotic 0.5 × 102 colony-forming units of GV injections each, while their littermate controls in the left horn received sterile saline injections. A second laparotomy was performed seven days later. Assessment of the fetal pups, histopathology of the placenta and histomorphometric examination of the fetal lung tissues was done.Results: Three dams with a combined total of 12 fetuses were exposed to intra-amniotic GV, and 9 fetuses were unexposed. The weights of fetuses, placenta, and fetal lung were significantly lower in the GV group than the saline-inoculated control group [mean gross weight, GV (19.8 ± 3.8 g) vs. control (27.9 ± 1.7 g), p < 0.001; mean placenta weight, GV (5.5 ± 1.0 g) vs. control (6.5 ± 0.7 g), p = 0.027; mean fetal lung weight, GV (0.59 ± 0.11 g) vs. control (0.91 ± 0.08 g), p = 0.002. There was a two-fold increase in the multinucleated syncytiotrophoblasts in the placenta of the GV group than their littermate controls (82.9 ± 14.9 vs. 41.6 ± 13.4, p < 0.001). The mean alveolar septae of GV fetuses was significantly thicker than the control (14.8 ± 2.8 μm vs. 12.4 ± 3.8 μm, p = 0.007). Correspondingly, the proliferative index in the interalveolar septum was 1.8-fold higher in the GV group than controls (24.9 ± 6.6% vs. 14.2 ± 2.9%, p = 0.011). The number of alveoli and alveolar surface area did not vary between groups.Discussion: Low-dose intra-amniotic GV injection induces fetal growth restriction, increased placental multinucleated syncytiotrophoblasts and fetal lung re-modeling characterized by alveolar septal hypertrophy with cellular proliferative changes.Conclusion: This intra-amniotic model could be utilized in future studies to elucidate the acute and chronic effects of GV intrauterine infections.

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N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung DevelopmentIn VivoandIn Vitro

BioMed Research International ◽

10.1155/2016/5843981 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Zhengchang Liao ◽

Xiaocheng Zhou ◽

Ziqiang Luo ◽

Huiyi Huo ◽

Mingjie Wang ◽

...

Keyword(s):

Lung Development ◽

Fetal Lung ◽

Lung Weight ◽

Mk 801 ◽

Fetal Lung Development ◽

Fetal Rat ◽

Intrauterine Hypoxia ◽

Excessive Activation

Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs) are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR’s expression and role in fetal lung development.Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E) 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801’s influence on intrauterine hypoxia-induced retardation of fetal lung development was testedin vivo, and NMDA’s direct effect on fetal lung development was observed using fetal lung organ culturein vitro.Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damagein vivo.In vitroexperiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression.Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

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Velocity and attenuation of sound in the isolated fetal lung as it is expanded with air

Journal of Applied Physiology ◽

10.1152/japplphysiol.00683.2004 ◽

2005 ◽

Vol 98 (6) ◽

pp. 2235-2241 ◽

Cited By ~ 12

Author(s):

Philip J. Berger ◽

Elizabeth M. Skuza ◽

C. Andrew Ramsden ◽

Malcolm H. Wilkinson

Keyword(s):

High Frequency ◽

Fetal Lung ◽

Acoustic Properties ◽

Lung Density ◽

Lung Weight ◽

Fetal Sheep ◽

High Frequency Sound ◽

Frequency Sound ◽

Isolated Lung ◽

Audible Sound

We measured the velocity and attenuation of audible sound in the isolated lung of the near-term fetal sheep to test the hypothesis that the acoustic properties of the lung provide a measure of the volume of gas it contains. We introduced pseudorandom noise (bandwidth 70 Hz–7 kHz) to one side of the lung and recorded the noise transmitted to the surface immediately opposite, starting with the lung containing only fetal lung liquid and making measurements after stepwise inflation with air until a leak developed. The velocity of sound in the lung fell rapidly from 187 ± 28.2 to 87 ± 3.7 m/s as lung density fell from 0.93 ± 0.01 to 0.75 ± 0.01 g/ml (lung density = lung weight/gas volume plus lung tissue volume). For technical reasons, no estimate of velocity could be made before the first air injection. Thereafter, as lung density fell to 0.35 ± 0.01 g/ml, there was a further decline in velocity to 69.6 ± 4.6 m/s. High-frequency sound was attenuated as lung density decreased from 1.0 to 0.5 g/ml, with little change thereafter down to a density of 0.35 ± 0.01 g/ml. We conclude that both the velocity of audible sound through the lung and the degree to which high-frequency sound is attenuated in the lung provide information on the degree of inflation of the isolated fetal lung, particularly at high lung densities. If studies of sound transmission through the lung in the intact organism were to confirm these findings, the acoustic properties of the lung could provide a means for monitoring lung aeration during mechanical ventilation of newborn infants.

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Endogenous opioids modulate fetal rabbit lung maturation

Journal of Applied Physiology ◽

10.1152/jappl.1987.62.6.2141 ◽

1987 ◽

Vol 62 (6) ◽

pp. 2141-2146 ◽

Cited By ~ 11

Author(s):

C. R. Comer ◽

J. S. Grunstein ◽

R. J. Mason ◽

S. C. Johnston ◽

M. M. Grunstein

Keyword(s):

Body Weight ◽

Fetal Lung ◽

Dry Weight ◽

Endogenous Opioids ◽

Opioid Antagonist ◽

Saline Control ◽

Lung Maturation ◽

Rabbit Lung ◽

Lung Weight ◽

Air Space

To test the hypothesis that endogenous opioids modulate fetal lung development, separate groups of pregnant rabbits received daily injections of saline, morphine (1 mg/kg body wt), or the opioid antagonist naloxone (0.4 and 5.0 mg) for 10 days during their last trimester of pregnancy. The corresponding groups of fetuses were then delivered prematurely on day 28 of gestation (term approximately 31 days) and evaluated with respect to differences in body weight, lung weight, and the ratios of wet to dry lung weight and lung dry weight to body weight, the static inflation and deflation air and saline pressure-volume (P-V) characteristics of the lungs, and lung morphology. Mean values for body weight, lung weight, and the ratios of lung wet to dry weight and lung dry weight to body weight were not significantly different among the saline control (C), morphine (M)-, and naloxone (NLX)-treated fetuses. On the other hand, the fetal air P-V curves varied significantly (P less than 0.001), wherein the M-treated group depicted increased lung distensibility and alveolar stability on lung deflation, whereas the opposite was obtained in the NLX-treated fetuses. Moreover, morphometric analyses demonstrated that the mean alveolar air space-to-tissue ratio in lungs from M-treated fetuses were significantly greater than that observed either in C or in NLX-treated fetuses (P less than 0.05); however, the air space-to-tissue ratio did not significantly vary between the C and NLX-treated animals. These observations provide new evidence that endogenous opioids enhance fetal lung maturation.

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Predictive value of fetal lung volume in prenatally diagnosed skeletal dysplasia

Prenatal Diagnosis ◽

10.1002/pd.4475 ◽

2014 ◽

Vol 34 (13) ◽

pp. 1326-1331 ◽

Cited By ~ 10

Author(s):

K. Nicole Weaver ◽

Jodie Johnson ◽

Beth Kline-Fath ◽

Xue Zhang ◽

Foong-Yen Lim ◽

...

Keyword(s):

Lung Volume ◽

Skeletal Dysplasia ◽

Predictive Value ◽

Fetal Lung

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New Ultrastructural Observations on Injury and Regeneration of Cilia in Mammalian Conducting Airway Epithelium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099544 ◽

1981 ◽

Vol 39 ◽

pp. 624-625

Author(s):

J.L. Carson ◽

A.M. Collier

Keyword(s):

Respiratory Tract ◽

Airway Epithelium ◽

Defense Mechanisms ◽

Normal Growth ◽

Fetal Lung ◽

Secretory Cells ◽

Airway Epithelial ◽

Ciliated Cells ◽

Conducting Airway ◽

Conducting Airways

The ciliated cells lining the conducting airways of mammals are integral to the defense mechanisms of the respiratory tract, functioning in coordination with secretory cells in the removal of inhaled and cellular debris. The effects of various infectious and toxic agents on the structure and function of airway epithelial cell cilia have been studied in our laboratory, both of which have been shown to affect ciliary ultrastructure.These observations have led to questions about ciliary regeneration as well as the possible induction of ciliogenesis in response to cellular injury. Classical models of ciliogenesis in the conducting airway epithelium of the mammalian respiratory tract have been based primarily on observations of the developing fetal lung. These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development.

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