Progressive Anatomical Closure of Foramen Ovale in Normal Neonatal Mouse Hearts by Colleen T. Cole-Jeffrey, Ryota Terada, Matthew R. Neth, Andy Wessels, and Hideko Kasahara. Anat Rec 295:764–768
Before birth, shunting of blood through the right atrium to the left atrium of the heart through the foramen ovale is important for survival. This allows bypassing the fetal pulmonary circulation. After birth, the lungs become functional and this flow between the atria ceases as the foramen ovale functionally closes, allowing separation of venous and arterial blood. Closure is achieved by fusion of the septum primum and septum secundum, along with other wall structures. However, the foramen ovale sometimes remains unsealed, which is called patent foramen ovale. Patent foramen ovale is associated with various problems, such as migraine with aura, cryptogenic stroke, and systemic arterial embolism. The process of closure of the foramen ovale in the postnatal heart is not well understood. The authors used the FVB/N mouse strain, which is often used for generation of transgenic mice, to investigate when interatrial communication normally occurs in mice. Using histological analysis and three-dimensional reconstruction, the authors examined heart tissue sections from postnatal day 2 to 3 months to determine the morphological changes associated with functional changes after pulmonary circulation was established. The authors established when right-to-left atrial communication occurs, as well as the timing of eventual fusion and closure. The implications of these findings are that they can be used to determine the postnatal time when genetically engineered mice models will be effective for studying abnormal interatrial communication and its mechanism(s).
The Prenatal Toxic Effect of Methylmercury on the Development of the Appendicular Skeleton of Rat Fetuses and the Protective Role of Vitamin E by Gamal S. Abd El-Aziz, Magdy M.O. El-Fark, and Hamid A.M. Saleh. Anat Rec 295:939–949
Methylmercury (MeHg) is a developmental neurotoxin, and its major source comes from contaminated seafood. One of the proposed mechanisms of action of MeHg toxicity is related to oxidative damage. Although many studies have investigated the effect of MeHg on reproduction and neurobehavior in offspring showing adverse effects, little is known regarding the effect of MeHg on the fetal skeleton. Bone growth in the fetus is sensitive to environmental conditions, which may adversely affect development of the fetal skeleton. Ultimately, these changes during fetal growth may affect bone mass and increase the risk of fractures in the adult. The authors investigated the effect of MeHg during pregnancy on the fetal rat skeleton. They also examined whether vitamin E, which is an effective liposoluble antioxidant, reduces this toxicity and improves fetal development. The authors showed that MeHg administration to pregnant rats decreased fetal growth parameters, such as fetal body weight, indicating intrauterine growth restriction. Maternal MeHg administration also caused delayed ossification and decreased long bone growth. Treatment with vitamin E at the same time as MeHg administration improved ossification and fetal growth. These findings suggest that vitamin E may ameliorate the adverse effects of MeHg toxicity during pregnancy. Studies are required to determine the long-term significance of MeHg toxicity on bone health.
Ontogeny of Proteolytic Signaling and Antioxidant Capacity in Fetal and Neonatal Diaphragm by Yong Song and J. Jane Pillow. Anat Rec 295:864–871
The diaphragm is an important muscle for spontaneous breathing. Infants born before normal term may have increased risk of respiratory muscle weakness because of immature structural and functional development of the diaphragm and intercostal muscles. Immaturity may also be further compromised by exposure before and after birth to factors, such as steroids, malnutrition, chorioamnionitis, or postnatal events. The mechanisms involved in the development of muscle weakness are poorly understood, but they are mainly thought to be caused by protein degradation. Little is known regarding the development of proteolytic signaling in the diaphragm in the fetus. The authors examined the ontogeny of proteolytic signaling and antioxidant capacity, using the fetal and postnatal lamb as a model. They measured gene and protein expression of key components of the proteolytic pathway (calpain, caspase 3, and ubiquitin proteasome) and of the oxidant defense pathway (glutathione peroxidase and sulfur-oxide dismutase) at midgestation and shortly after birth in diaphragm muscle. The authors found that proteolytic signaling decreased toward the end of gestation, whereas antioxidant capacity increased. After birth, most of the proteolytic genes and proteins were upregulated and antioxidant genes were downregulated from 24 h to 7 weeks after birth. These findings indicate that proteolytic signaling and antioxidant capacity can adapt to metabolic changes and muscle maturation during perinatal development. Their data will be useful for future studies on the immature diaphragm to better understand why preterm infants are susceptible to respiratory failure from mechanical ventilation or other stressful factors, such as inflammation.