A single dose of clothianidin exposure induces varying sex-specific behavioral changes in adulthood depending on the developmental stage of its administration.

Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.

Quantitative and qualitative evaluations of fetal lung with MR imaging.

PURPOSE: To measure both volume and signal intensity of the fetal lung at magnetic resonance (MR) imaging and to evaluate the clinical use of this method to predict fetal pulmonary hypoplasia. MATERIALS AND METHODS: A total of 87 fetuses evaluated with MR imaging at 24-39 weeks of gestation were classified into a control group with good respiratory outcome (group A, n = 58) or a poor outcome group with severe respiratory disturbance after birth (group B, n = 29). Planimetric measurement of total lung volume and calculation of the ratio of lung signal intensity to spinal fluid signal intensity (L/SF) were performed on MR images by using region-of-interest analysis. Regression analysis, analysis of covariance, analysis of variance, and receiver operating characteristic (ROC) analysis were performed. RESULTS: The best fit for group A lung volume was represented by the regression line V = (2.41 x G) - 37.6 (r = 0.537, P <.001), in which V is lung volume and G is gestational weeks; that for group B, by V = (0.97 x G) - 14.0 (r = 0.378, P <.05). Results of analysis of covariance with gestational weeks used as a covariate showed a significant difference in lung volume between the two groups (P <.001). Mean +/- SEM for L/SF ratio was 0.817 +/- 0.013 and 0.598 +/- 0.019 in groups A and B, respectively (P <.001). For prediction of postnatal respiratory outcome, the area under the ROC curve for lung volume and L/SF ratio combined was 0.990, significantly higher than that for lung volume alone (P <.05). CONCLUSION: Simultaneous measurement of fetal lung volume and signal intensity on MR images is a promising method for predicting fetal pulmonary hypoplasia.

Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy.

OBJECTIVE: Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it is also secreted in the placenta and is probably a cause of pre-eclampsia. To provide a basis for elucidation of the relationship between pre-eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood. METHODS: Fifty-nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8-20 weeks' gestation (early), 11 at 28-34 weeks (middle) and 24 at 35-40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method. RESULTS: The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood. CONCLUSION: This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.

Application of lung volume measurement by three-dimensional ultrasonography for clinical assessment of fetal lung development.

OBJECTIVE: To prepare nomograms for normal fetal lung volume using three-dimensional ultrasonography and to evaluate the possibility of clinical applications of this procedure. METHODS: One hundred twenty-five healthy neonates with birth weights within +/-1.5 SD (group A), 9 neonates with intrauterine growth restriction (birth weight less than -1.5 SD) but no severe respiratory disturbance at birth (group B), and 10 neonates with severe respiratory disturbance but no intrauterine growth restriction (group C) were studied. With the use of a three-dimensional ultrasonographic device, continuous B-mode images centering on the fetal thorax were acquired as volume data. Analytical software was used to repeatedly trace the contours of bilateral fetal lungs on transverse slices to calculate the lung volume. RESULTS: In group A, the total volume of normal fetal lungs can be expressed by the second-degree regression equation: 0.08 x (gestational week - 30.1)2 + 3.28 x gestational week - 67.2 (R = 0.909; P < .001). The lung volumes of groups B and C were below the 25th and 2.5th percentiles, respectively, of this regression curve. For the same case, the lung volume increased with gestational week in group B but remained unchanged or even decreased in group C. The total volume of normal fetal lungs can also be expressed by the linear regression equation: 0.02 x estimated fetal weight + 0.29 (R = 0.902). The lung volumes of groups B and C were distributed below and above, respectively, the 2.5th percentile of the regression line. CONCLUSIONS: This analytical method may be applied to evaluate lung development.