No abstract

Using immunohistochemical staining, the distribution of connexin40 (Cx40) and connexin43 (Cx43) was studied in rat, guinea pig, porcine, bovine and human hearts. These species display differences in the degree of morphological differentiation of the conduction system. This study was performed in the anticipation that comparison of the distributions of Cx40 and Cx43 in young and adult specimens may provide clues as to the physiological role of connexins in the heart. To a large extent, the distribution patterns of Cx40 and Cx43 are comparable between species. In neonates and adults, Cx43 was immunolocalized throughout the working myocardium, but in the conduction system Cx43 was detected only after birth. Cx40 was found to appear slightly earlier in development than Cx43 and to disappear when levels of Cx43 became more abundant. This time course was seen in working myocardium and in the ventricular conduction system. Together these data suggest that expression of Cx40 induces or facilitates expression of Cx43, while abundant expression of Cx43 in turn leads to suppression of Cx40 expression. The exceptions to this may represent blocks in this potential regulatory sequence. A second conclusion is that Cx40 and Cx43 containing gap junctions appear in the ventricular conduction system from distal to proximal and only after birth. This indicates that terminal differentiation of the conduction system occurs unexpectedly late in development.

Rat (Rattus norvegicus) and spiny mouse (Acomys cahirinus) are closely related murinoid species that mainly differ in the developmental timing of birth. A comparison between the developmental profiles of some characteristic enzymes of the liver of both species was carried out to elucidate the question to what extent are these enzymic profiles and hence the maturation of the liver related to the timing of birth? It was found that these organotypic enzymes first become detectable at the same developmental stage in both species. Likewise, the weaning phase of the enzymic profiles occurs at the same developmental time point in both species. It is argued that both the first appearance and the weaning increase in enzyme activity levels occur at endogenously programmed timepoints with only superimposed effects of hormones. In contrast, the perinatal phase of the enzymic profile is completely dependent on the developmental timing of birth and therefore appears not to be anchored to a particular developmental timepoint, but rather to be dependent on birth-associated (hormonal) adaptation. In accordance with this hypothesis it was found that the morphological development of the liver proceeded independent of the timing of birth. Furthermore, the hormonal regulation of the investigated enzymes was found to be the same in both species. Despite the more advanced state of morphological development of the liver in the spiny mouse at birth, it was found that the inducibility of organotypic gene expression by hormones in spiny mouse fetuses was as limited as in rat fetuses. This observation therefore suggests that the intra-uterine environment is responsible for the limited inducibility of enzymes before birth.

Rat (Rattus norvegicus) and spiny mouse (Acomys cahirinus) are closely related murine species that, due to their altricial (rat) and precocial (spiny mouse) modes of development, differ in the developmental timing of birth. A comparison between the developmental profiles of plasma glucagon, insulin, thyroxine, triiodothyronine, and glucocorticosteroid hormone was carried out to elucidate the question to what extent these hormonal profiles were related to the timing of birth. Although corticosterone is the major circulating glucocorticosteroid in rat, only cortisol was found in the spiny mouse. The onset of increases in glucocorticosteroid and thyroid hormone levels occurred at the same developmental time points in both species. A neonatal increase in triiodothyronine levels was observed in the spiny mouse only. In both species the immediate perinatal period was characterized by decreases in the ratio of insulin and glucagon levels and the level of glucocorticosteroids. The observed developmental patterns of hormonal levels were found to be consistent with the observed developmental pattern of enzymic maturation in the respiratory and gastrointestinal tract, which play a critical role in the adaptation to the extrauterine environment.