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A two-generation reproductive toxicity study was performed to evaluate the effects of diethyl phthalate on parental reproductive performance, including features of the endocrine system and development and growth of offspring at dietary dose levels of 0, 600, 3000 and 15000 ppm. In F0 and F1 parents, no treatment-related adverse effects were observed in clinical findings, body weights, food consumption, reproductive parameters, and gross or histopathological findings in any treated group. Increased liver weights and enhanced activities of metabolic enzymes were observed in F0 males at 15000 ppm. F0 males also exhibited an increase in the content of CYP3A2, a cytochrome P450 isozyme, at 15000 ppm, and a decrease in the levels of serum testosterone at 3000 and 15000 ppm, suggesting sex steroid metabolism might be changed. However, these were not considered adverse effects because the degree of change was too slight to affect the reproductive capability to produce progeny. Body weight gains before weaning were inhibited in F1 and F2 pups and vaginal opening was slightly delayed in F1 females at 15000 ppm. No changes were observed in the reproductive performance. Therefore, the no-observed-adverse-effect level (NOAEL) from this study is considered to be 15000 ppm for parental animals, and 3000 ppm for development and growth of the pups.

Assessment of long-axis systolic function by TDI and M-mode echocardiography enables estimation of LVEF even in patients with poor IQ.

Array-based comparative genomic hybridization identified a 2.3-Mb microdeletion of 17p13.2p13.1 in a boy presenting with moderate mental retardation, intractable epilepsy and dysmorphic features. This deletion region was overlapped with the previously proposed shortest region overlapped for microdeletion of 17p13.1 in patients with mental retardation, microcephaly, microretrognathia and abnormal magnetic resonance imaging (MRI) findings of cerebral white matter, in which at least 17 known genes are included. Among them, DLG4/PSD95, GPS2, GABARAP and KCTD11 have a function in neuronal development. Because of the functional importance, we paid attention to DLG4/PSD95 and GABARAP, and analyzed zebrafish in which the zebrafish homolog of human DLG4/PSD95 and GABARAP was knocked down and found that gabarap knockdown resulted in small head and hypoplastic mandible. This finding would be similar to the common findings of the patients with 17p13.1 deletions. Although there were no pathogenic mutations in DLG4/PSD95 or GABARAP in a cohort study with 142 patients with idiopathic developmental delay with/without epilepsy, further studies would be required for genes included in this region.