Calcitonin gene-related family peptides in vascular adaptations, uteroplacental circulation, and fetal growth

Maternal vascular adaptations, implantation of embryo, and placental growth and development are crucial for overall well-being of the fetus and are controlled by a range of signals, including growth factors and steroid hormones. The calcitonin (CT)/calcitonin gene-related peptide (CGRP) family peptides have been the focus of emerging studies, and these peptides appear to mediate some of the critical functions during pregnancy. Three peptides of the CT/CGRP family, CGRP, adrenomedullin, and intermedin, working through their overlapping receptor components, exert significant positive effects on vascular adaptations during pregnancy, uteroplacental vascular functions, and fetal growth. Many of the effects of these peptides are regulated by sex steroid hormones. Use of peptide antagonist in animals, together with genetic animal models, strongly implicates the importance of these 3 peptides in human pregnancy and related complications. However, insights into the underlying mechanisms of their actions on fetal-placental growth are limited by the lack of specificity of currently available antagonists. Future studies with specific knockdown of receptor components and/or peptides should be helpful for better understanding of these mechanisms and for the development of target-specific therapies to prevent pregnancy complications.