Expression and function of the LIM homeobox containing genes Lhx3 and Lhx4 in the mouse placenta

The LIM homeobox containing genes of the LIM-3 group, Lhx3 and Lhx4 , are critical for normal development. Both genes are involved in the formation of the pituitary and the motoneuron system and loss of either gene causes perinatal lethality. Previous studies had shown that Lhx3 is overexpressed in hyperplastic placentas of mouse interspecies hybrids. To determine the role of LHX3 in the mouse placenta, we performed expression and function analyses. Our results show that Lhx3 exhibits specific spatial and temporal expression in the mouse placenta. However, deletion of Lhx3 does not produce a placental phenotype. To test whether this is due to functional substitution by Lhx4 , we performed a phenotype analysis of Lhx3 −/−; Lhx4 −/− double-mutant placentas. A subset of Lhx3 −/−; Lhx4 −/− placentas exhibited abnormal structure of the labyrinth. However, absence of both LIM-3 genes did not interfere with placental transport nor consistently with expression of target genes such as Gnrhr . Thus, LHX3 and LHX4 appear to be dispensable for placental development and function. Developmental Dynamics 237:1517-1525, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58577/1/21546_ftp.pd

Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice

The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice.These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health

Fetal growth restriction in preterm infants and cardiovascular function at five years of age

Objectives We have previously reported an increased cardiac workload in newborn preterm small (SGA) infants, but not in infants appropriate for gestational age (AGA). We hypothesized that these cardiovascular changes win persist at follow-tip at 5 years of age. Study design We assessed blood pressure, echocardiography, and shin perfusion with laser Doppler flowmetry in 22 SGA (S21 +/- 248 g. 28.5 +/- 2:5 gestational weeks) and in 25 AGA (1065 +/- 241 g, 27.6 +/- 0.8 weeks) preterm children at age 5 years. Laser Doppler flowmetry also was used in 13 control children (3982 +/- 425 g, 40.4 +/- 1.8 weeks). Results The preterm children in both the SGA and AGA groups had similar higher systolic blood pressures, increased interventricular septum thicknesses, and smaller left ventricular end-diastolic diameters compared with population reference values. Maximal endothelium-independent perfusion to sodium nitroprusside was higher and maximal endothelium-dependent perfusion to acetylcholine reached a plateau earlier in the AGA preterm group than in the control group. Conclusions Prematurity may, impair cardiovascular function independently of intrauterine growth restriction. Altered cardiac dimensions and differences in perfusion responses may reflect increased cardiac afterload

Accuracy of the volume and pressure displays of high frequency oscillators

Objective: To determine the effect of frequency on the accuracy of volume and pressure displays of high frequency oscillators. Methods: The effect of frequency on the displayed volume of the Stephanie, Dräger Babylog 8000 Plus, and SLE 5000 oscillators was assessed. A sine wave pump delivered a constant tidal volume at frequencies of 5–15 Hz to the patient manifold of the oscillators. The displayed volumes at each frequency were compared with the delivered volume. The effect of frequency on displayed pressure was assessed by connecting the oscillator's patient manifold to a lung model; three types of oscillator were studied (SensorMedics 3100A, SLE 5000, and Stephanie). Airway pressure was measured from the manifold using a pressure transducer and non-compliant tubing; the pressure measuring system had a flat frequency response to 30 Hz. Results: The SLE 5000 volume display overread the delivered volume (by about 5%), but was not affected by frequency. At 5 Hz, the Dräger Babylog 8000 Plus and the Stephanie underread the delivered volume (by about 20%). Increasing frequency resulted in a greater discrepancy between the delivered and displayed volume with the Stephanie, but a smaller discrepancy with the Dräger Babylog 8000 Plus. Altering frequency had a small effect (maximum difference 6%) on the relation between the displayed and delivered pressure for all three oscillators. Conclusion: Frequency affects the accuracy of displayed volumes and, to a lesser extent, displayed pressures of high frequency oscillators. The results emphasise that data displayed by new devices should not be uncritically accepted