Placental vascular defects in compromised pregnancies: effects of assisted reproductive technologies and other maternal stressors

Many factors negatively affect pregnancy establishment and subsequent fetal growth and development, including maternal factors such as nutritional stress, age, body mass index, and genetic background, and external factors including environmental stress, psychosocial stress, multiple fetuses, medical conditions (e.g., polycystic ovary syndrome), lifestyle choices (e.g., alcohol consumption, smoking), and assisted reproductive technologies. These same factors have similar consequences for placental growth and development, including vascular development. We and others have shown that placental vascular development begins very early in pregnancy and determines, to a large extent, placental function—that is, the magnitude of the increase in placental blood flow and thus nutrient transport to the fetus. During the peri-implantation period and also later in pregnancy, cloned (somatic cell nuclear transfer) embryos exhibit a variety of placental defects including reduced vascularization and altered expression of angiogenic factors. Although placental defects are less pronounced in pregnancies resulting from the transfer of in vitro fertilized embryos, we and others have recently demonstrated that vascularization, expression of angiogenic factors, sex steroid receptors, several epigenetic markers, and growth of utero-placental tissues all were altered during early pregnancy after transfer of embryos obtained through natural mating, in vitro fertilization, or other assisted reproductive techniques. These observations are in agreement with the recent reports that in humans even singleton pregnancies established with assisted reproductive techniques are at increased risk of preterm delivery and low birth weight, and seem especially relevant considering the rapidly expanding use of these techniques in humans and animals

The effect of gestational age on angiogenic gene expression in the rat placenta

The placenta plays a central role in determining the outcome of pregnancy. It undergoes changes during gestation as the fetus develops and as demands for energy substrate transfer and gas exchange increase. The molecular mechanisms that coordinate these changes have yet to be fully elucidated. The study performed a large scale screen of the transcriptome of the rat placenta throughout mid-late gestation (E14.25-E20) with emphasis on characterizing gestational age associated changes in the expression of genes invoved in angiogenic pathways. Sprague Dawley dams were sacrificed at E14.25, E15.25, E17.25 and E20 (n = 6 per group) and RNA was isolated from one placenta per dam. Changes in placental gene expression were identifed using Illumina Rat Ref-12 Expression BeadChip Microarrays. Differentially expressed genes (>2-fold change

Cardiac Functions of Voltage-Gated Ca2+ Channels: Role of the Pharmacoresistant Type (E-/R-Type) in Cardiac Modulation and Putative Implication in Sudden Unexpected Death in Epilepsy (SUDEP)

Voltage-gated Ca2+ channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/ pacemaker activity due to intracellular Ca2+ transients. In the myocardium, the Cayl subfamily (L-type: C41.2 and C41.3) is the main contributor to excitation contraction coupling and/or pacemaking, whereas the Ca(v)3 subfamily (T-type: Cay3.1 and Cay3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Ca(v)2 family (E-/R-type: Ca(v)2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Ca(v)2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed