A possible association between ART and BWS/SRS was found, and we observed a more widespread disruption of genomic imprints after ART. The increased frequency of imprinting disorders after ART is perhaps not surprising given the major epigenetic events that take place during early development at a time when the epigenome is most vulnerable.

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Maternal fish consumption brings both risks and benefits to the fetus from the standpoint of methylmercury (MeHg) and n-3 PUFA (polyunsaturated fatty acids). MeHg is one of the most risky substances to come through fish consumption, and mercury concentrations in red blood cells (RBC-Hg) are the best biomarker of MeHg exposure. Docosahexaenoic acid (DHA, C22:6n-3), which is one of the most important fatty acids for normal brain development and function, is also derived from fish consumption. Our objective in this study was to examine the relationships between RBC-Hg and plasma fatty acid composition in mother and fetus at parturition. Venous blood samples were collected from 63 pairs of mothers and fetuses (umbilical cord blood) at delivery. In all cases, fetal RBC-Hg levels were higher than maternal RBC-Hg levels. The geometric mean of fetal RBC-Hg was 13.4 ng/g, which was significantly (p < 0.01) higher than that of maternal RBC-Hg (8.41 ng/g). While the average fetal/maternal RBC-Hg ratio was 1.6, the individual ratios varied from 1.08 to 2.19, suggesting considerable individual differences in MeHg concentrations between maternal and fetal circulations at delivery. A significant correlation was observed between maternal and fetal DHA concentrations (r = 0.37, p < 0.01). Further, a significant correlation was observed between RBC-Hg and plasma DHA in fetus (r = 0.35, p < 0.01). These results confirm that both MeHg and DHA which originated from fish consumption transferred from maternal to fetal circulation and existed in the fetal circulation with a positive correlation. Pregnant women in particular need not give up eating fish to obtain such benefits. However, they would do well to at least consume smaller fish, which contain less MeHg, thereby balancing the risks and benefits from fish comsumption.

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Hemoglobin (Hb)-based artificial oxygen carriers are supposed to induce vasoconstriction through the inactivation of endothelium-derived relaxing factor (EDRF). We examined the vasoconstrictive activity of acellular Hb and cellular Hb solutions in rabbit aortic strips. Unmodified Hb, pyridoxalated Hb, bovine unmodified Hb, haptoglobin-Hb complex (Hp-Hb), and polyoxyethylene glycol-conjugated Hb (PEG-Hb) were used as acellular Hbs having different molecular masses. Cellular Hbs included liposome-encapsulated Hb and red blood cells (RBC). In the first experiment, Hb (10 ng/ml to 1 mg/ml) was cumulatively added to the tissues in which steady-state relaxation was evoked by acetylcholine (ACh) after precontraction induced by phenylephrine. Although all Hb solutions induced a dose-dependent reversal of ACh-induced relaxation, the most potent vasoconstrictive effect was noted with acellular Hbs, and their contractile activities were almost the same independent of molecular mass. On the other hand, liposome-Hb and RBC showed reduced potencies in this order. These results indicate the importance of cellularity as the major factor determining Hb-related EDRF inactivation. In another experiment, the tissues were exposed to Hb at 0.01, 0.1, or 1 mg/ml for 30 min and ACh-induced relaxation was recorded after the complete removal of Hb in an organ bath chamber. Exposure to unmodified Hb at > 0.1-mg/ml concentrations significantly reduced the ACh-induced relaxation, whereas the relaxation was not affected by PEG-Hb, Hp-Hb, liposome-Hb, or RBC. These results suggest that unmodified Hb might be persistently associated with tissues and thereby inhibit ACh-induced relaxation. From these findings, we propose two attributes of Hb-related inhibition of endothelium-dependent relaxation: Acellular Hbs inhibit EDRF more efficiently in the luminal space than cellular Hbs, and unmodified Hb can also inhibit it adluminally and/or adventitially.

Microphthalmia-associated transcription factor (Mitf) is required for the differentiation of melanoblasts of the neural crest origin. The mouse homozygous for the black-eyed white (Mitf mi-bw ) allele is characterized by white-coat color and deafness with black eye, due to the loss of melanoblasts during embryonic development. The Mitf mi-bw allele carries an insertion of long interspersed element-1 (L1) in intron 3 of the Mitf gene, which may cause the deficiency of melanocyte-specific Mitf-M. Here, we show that the L1 insertion results in the generation of alternatively spliced Mitf-M mRNA species, such as Mitf-M mRNA lacking exon 3, exon 4 or both exons 3 and 4, each of which encodes Mitf-M protein with an internal deletion. Transient expression assays showed the loss of or reduction in function of each aberrant Mitf-M protein and the dominant negative effect of Mitf-M lacking exon 4 that encodes an activation domain. Thus, the L1 insertion may decrease the expression level of functional Mitf-M. Importantly, Mitf-M mRNA is expressed in the wild-type mouse brain, with the highest expression level in the hypothalamus. Likewise, aberrant Mitf-M mRNAs are expressed in the bw mouse brain. The bw mice show the altered neurobehavior under a stressful environment, suggesting the role of Mitf-M in sensory perception.

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