Good day, Ma'am Leonardo. Here are our answers to your questions po:
1. Are there mechanical or chemical factors that could lead to accidentally upsetting hypoxic conditions to the detriment of development of the cardiovascular system?
One way of upsetting normal hypoxic conditions is by inducing severe hypoxia (5-7.5% oxygen) through uterine constriction and bradycardia. Various activities can lead to the phenomenon, one of which is the administration of drugs with almokalant and dofetilide that deliberately slow or stop the embryonic heart for a short period of time. It was also discovered that phenytoin caused a concentration-dependent slowing and arrhythmia of the embryonic heart of in vitro-grown rat embryos (Webster & Abela, 2007).
Constriction of the uterine vessel is one mechanical factor influencing hypoxic conditions. Cocaine use in pregnancy, for example, can cause severe uterine artery constriction that could lead to hypoxia-related malformations. In this case, the uterus and the enclosed embryos are deprived of blood for the duration of the constriction, resulting in severe hypoxia. Surviving fetuses may have malformations, such as heart defects and situs inversus (Webster & Abela, 2007).
2. Would a slight change in hypoxic levels bring about abnormal development? Up to what stage in the cardiovascular development should the hypoxic condition be maintained?
Modest degrees of changes in hypoxia are tolerated by the embryo, but more extreme alterations in hypoxia levels will result in a variety of developmental changes. For example, inadequate exposure to normal hypoxia lowers the expression of essential genes required for heart and vascular development, like that of which encodes for hypoxia-inducible factor or HIF. Furthermore, chronic exposure to moderate abnormal hypoxia can lead to programming of cardioprotective genes, which may impair the capacity of heart to adjust to stresses later in life, and more severe abnormal hypoxia can have a substantial impact on the development of embryonic cardiomyocytes, which can lead to cardiomyopathy (Patterson and Zhang, 2010).
Dunwoodie (2009) posited that modification of the HIF activity up to the chamber formation stage is considered to be lethal on the development of the cardiovascular system. It was discovered in the same study that this change resulted in the following effects: the morphogenesis is halted at the looping stage, there is occurrence of hypoplasia, absence of trabeculation, and impaired neural crest cell migration. Thus, it is important that for a normal cardiovascular system development that the hypoxic condition is maintained up to the chamber formation stage,
References:
Dunwoodie, S. L. (2009). The Role of Hypoxia in Development of the Mammalian Embryo. Developmental Cell, 17(6), 755–773. https://doi.org/10.1016/j.devcel.2009.11.008
Patterson, A. J., & Zhang, L. (2010). Hypoxia and fetal heart development. Current molecular medicine, 10(7), 653–666. https://doi.org/10.2174/156652410792630643
Webster, W. S., & Abela, D. (2007). The effect of hypoxia in development. Birth defects research. Part C, Embryo today : reviews, 81(3), 215–228. https://doi.org/10.1002/bdrc.20102
1. Are there mechanical or chemical factors that could lead to accidentally upsetting hypoxic conditions to the detriment of development of the cardiovascular system?
One way of upsetting normal hypoxic conditions is by inducing severe hypoxia (5-7.5% oxygen) through uterine constriction and bradycardia. Various activities can lead to the phenomenon, one of which is the administration of drugs with almokalant and dofetilide that deliberately slow or stop the embryonic heart for a short period of time. It was also discovered that phenytoin caused a concentration-dependent slowing and arrhythmia of the embryonic heart of in vitro-grown rat embryos (Webster & Abela, 2007).
Constriction of the uterine vessel is one mechanical factor influencing hypoxic conditions. Cocaine use in pregnancy, for example, can cause severe uterine artery constriction that could lead to hypoxia-related malformations. In this case, the uterus and the enclosed embryos are deprived of blood for the duration of the constriction, resulting in severe hypoxia. Surviving fetuses may have malformations, such as heart defects and situs inversus (Webster & Abela, 2007).
2. Would a slight change in hypoxic levels bring about abnormal development? Up to what stage in the cardiovascular development should the hypoxic condition be maintained?
Modest degrees of changes in hypoxia are tolerated by the embryo, but more extreme alterations in hypoxia levels will result in a variety of developmental changes. For example, inadequate exposure to normal hypoxia lowers the expression of essential genes required for heart and vascular development, like that of which encodes for hypoxia-inducible factor or HIF. Furthermore, chronic exposure to moderate abnormal hypoxia can lead to programming of cardioprotective genes, which may impair the capacity of heart to adjust to stresses later in life, and more severe abnormal hypoxia can have a substantial impact on the development of embryonic cardiomyocytes, which can lead to cardiomyopathy (Patterson and Zhang, 2010).
Dunwoodie (2009) posited that modification of the HIF activity up to the chamber formation stage is considered to be lethal on the development of the cardiovascular system. It was discovered in the same study that this change resulted in the following effects: the morphogenesis is halted at the looping stage, there is occurrence of hypoplasia, absence of trabeculation, and impaired neural crest cell migration. Thus, it is important that for a normal cardiovascular system development that the hypoxic condition is maintained up to the chamber formation stage,
References:
Dunwoodie, S. L. (2009). The Role of Hypoxia in Development of the Mammalian Embryo. Developmental Cell, 17(6), 755–773. https://doi.org/10.1016/j.devcel.2009.11.008
Patterson, A. J., & Zhang, L. (2010). Hypoxia and fetal heart development. Current molecular medicine, 10(7), 653–666. https://doi.org/10.2174/156652410792630643
Webster, W. S., & Abela, D. (2007). The effect of hypoxia in development. Birth defects research. Part C, Embryo today : reviews, 81(3), 215–228. https://doi.org/10.1002/bdrc.20102