Vitamin B6 deficiency in new born rats affects hepatic cardiolipin composition and oxidative phosphorylation

Vitamin B6 deficiency during pregnancy translates into a severe vitamin B6 deficiency (plasma levels decreased by 97%) in new-born rats. Further, hallmarks are increased (+89%) concentrations of homocysteine, gross changes in gene methylation and expression, and metabolic alterations including lipid metabolism. This study focuses on determining the effects of vitamin B6-deficiency on cardiolipin composition and oxidative phosphorylation in liver. For this purpose, hepatic cardiolipin composition was analyzed by means of LC/MS/MS, and mitochondrial oxygen consumption was determined by using a Clark-type electrode in a rat model of vitamin B6 deficiency. Liver mitochondria from new-born rats with pre-term vitamin B6 deficiency responded with substantial alterations in cardiolipin composition that include the following changes in the amounts of cardiolipin incorporated fatty acids: increase in C16, decrease in C18, decrease in saturated fatty acid, as well as increase in amount of oxidized cardiolipin species. These changes were accompanied by significantly decreased capacity of oxidative phosphorylation. In conclusion, vitamin B6 deficiency in new born rats induces massive alterations of cardiolipin composition and function of liver mitochondria. These findings support the importance of sufficient periconceptional supply of vitamin B6 to prevent vitamin B6 deficiency. Impact statement Vitamin B6 (VitB6) is an active co-enzyme for more than 150 enzymes and is required for a great diversity of biosynthesis and metabolic reactions. There is an increased need for VitB6 during pregnancy and sufficient supply of VitB6 is crucial for the prevention of cleft palate and neural tube defects. We show that liver mitochondria from new-born rats with pre-term VitB6 deficiency respond with substantial alterations in cardiolipin (CL) composition and in the amount of oxidized CL species. These changes are associated with a decrease in the efficiency of oxidative phosphorylation. The results of this study support the significance of sufficient supply of VitB6 during pregnancy (and periconceptional) for diminishing the number of early abortions and minimizing malformation. The established link between VitB6 deficiency, CL composition, and mitochondrial respiration/energy production provides mechanistic insight as to how the VitB6 deficiency translates into the known pathophysiological and clinically relevant conditions

The role of apoptosis in early embryonic development of the adenohypophysis in rats

Abstract Background Apoptosis is involved in fundamental processes of life, like embryonic development, tissue homeostasis, or immune defense. Defects in apoptosis cause or contribute to developmental malformation, cancer, and degenerative disorders. Methods The developing adenohypophysis area of rat fetuses was studied at the embryonic stage 13.5 (gestational day) for apoptotic and proliferative cell activities using histological serial sections. Results A high cell proliferation rate was observed throughout the adenohypophysis. In contrast, apoptotic cells visualized by evidence of active caspase-3, were detected only in the basal epithelial cones as an introducing event for fusion and closure of the pharyngeal roof. Conclusion We can clearly show an increasing number of apoptotic events only at the basic fusion sides of the adenohypophysis as well as in the opening region of this organ. Apoptotic destruction of epithelial cells at the basal cones of the adenohypophysis begins even before differentiation of the adenohypophyseal cells and their contact with the neurohypophysis. In early stages of development, thus, apoptotic activity of the adenohypophysis is restricted to the basal areas mentioned. In our test animals, the adenohypophysis develops after closure of the anterior neuroporus.</p

Morphometric characteristics of anencephalic skulls – A comparative study

Anencephaly is the most severe form of a neural tube defect resulting from the incomplete occlusion of the anterior neuropore in the fourth week of development and associated with a severely underdeveloped brain mass. As desmal ossification of the neurocranium is induced by the presence of soft tissues (brain), no bone develops as direct consequence of the missing brain. The cranial base, by contrast, is formed by chondral ossification, which is genetically determined, and thus present also in anencephaly. Morphometric characteristics of anencephalic skulls, however, have not yet been investigated in sufficient detail before. In this study we therefore comparatively assessed macroscopic morphological-anatomical and cephalometric CT data on structures and dimensions of 11 macerated anencephalic and 4 normal neonatal skulls highlighting skeletal morphological differences. The most striking results were the missing skullcap and the greatly changed morphology of the existing skull bones, which were reduced in size. The parameters of the skull base, the transverse orbital diameter and maxillary width were significantly smaller in anencephalic skulls. The morphology of the viscerocranium appeared similar to that of normal neonatal skulls. The results of this study can be used in diagnosis and skeletal classification for anencephaly. This can help identify bones that are incomplete, fragmented and taphonomically altered, which is often the case in historical and forensic studies. (C) 2020 Elsevier GmbH. All rights reserved