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Macrophages are found throughout reproductive tissues. To determine their role(s), we have studied mice homozygous for a null mutation (Csfm(op)) in the gene encoding the major macrophage growth factor, colony-stimulating factor-1 (CSF-1). Both male and female Csfm(op)/Csfm(op) mice have fertility defects. Males have low sperm number and libido as a consequence of dramatically reduced circulating testosterone. Females have extended estrous cycles and poor ovulation rates. CSF-1 is the principal growth factor regulating macrophage populations in the testis, male accessory glands, ovary, and uterus. However, analyses of CSF-1 nullizygous mice suggest that the primary reproductive defect is in the development of feedback regulation of the hypothalamic-pituitary axis. Although not correlating with deficiencies of microglia populations, electrophysiological investigations indicate an impairment of neuronal responses. This suggests that microglia, under the influence of CSF-1, act to organize neuronal connectivity during development and that the absence of this function results in a perturbation of the hypothalamic-pituitary-gonadal axis. Macrophages also appear to have functions in the differentiated tissues of the reproductive system, including having a positive influence on steroidogenic cells. These data suggest that macrophages, through their trophic functions, can be considered as essential accessory cells for normal reproductive functioning.

Aim: Current guidelines recommended adequate nutritional support for patients with liver cirrhosis to improve clinical outcome and quality of life (QOL). However, these evidences were obtained more than 10 years ago when malnutrition prevailed. In recent years, the impact of obesity on liver damage and carcinogenesis has grown. We attempted to elucidate the nutritional state and QOL in present cirrhotics. Anthropometry, blood biochemistry and indirect calorimetry were conducted, and QOL was measured using Short Form-8. Methods: Results:The mean body mass index (BMI) of all patients was 23.1 1 3.4 kg/m 2 , and 31% showed obesity (BMI 3 25.0). In subjects without ascites, edema or HCC, mean BMI was 23.6 1 3.6, and 34% had obesity. Protein malnutrition defined as serum albumin of less than 3.5 g/dL and energy malnutrition as respiratory quotient of less than 0.85 appeared in 61% and 43%, respectively, and protein-energy malnutrition (PEM) in 27% of all subjects. Among subjects without HCC, each proportion was 67%, 48% and 30%, respectively. QOL was significantly lower on all subscales than Japanese national standard values, but was similar regardless the presence or absence of HCC. Conclusion:While PEM is still present in liver cirrhosis, an equal proportion has obesity in recent patients. Thus, in addition to guidelines for PEM, establishment of nutrition and exercise guidelines seems essential for obese patients with liver cirrhosis.

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Evaluation methods for determining the distribution of transgene expression in the body and the in vivo fate of viral and non-viral vectors are necessary for successful development of in vivo gene delivery systems. Here, we evaluated the spatial distribution of transgene expression using tissue clearing methods. After hydrodynamic injection of plasmid DNA into mice, whole tissues were subjected to tissue clearing. Tissue clearing followed by confocal laser scanning microscopy enabled evaluation of the three-dimensional distribution of transgene expression without preparation of tissue sections. Among the tested clearing methods (ClearT2, SeeDB, and CUBIC), CUBIC was the most suitable method for determining the spatial distribution of transgene expression in not only the liver but also other tissues such as the kidney and lung. In terms of the type of fluorescent protein, the observable depth for green fluorescent protein ZsGreen1 was slightly greater than that for red fluorescent protein tdTomato. We observed a depth of ~1.5 mm for the liver and 500 μm for other tissues without preparation of tissue sections. Furthermore, we succeeded in multicolor deep imaging of the intracellular fate of plasmid DNA in the murine liver. Thus, tissue clearing would be a powerful approach for determining the spatial distribution of plasmid DNA and transgene expression in various murine tissues.