Β3-Adrenergic Receptors and Prematurity-Related Diseases: A Systematic Review

Background: β3 adrenergic receptors (β3-ARs) have recently gained scientific attention due to their widespread body expression and their heterogeneous span of tissue-related functions. Recent research has hypothesized their involvement in the pathogenesis of some of the most common complications in preterm infants. The aim of the present systematic review is to examine the published scientific literature on the topic. Methods: PubMED/Medline and Cochrane databases were searched for studies reporting an association between β3-ARs, fetal development, and preterm newborns' diseases. Results: Of 1596 articles found, 16 studies were selected for the review. Data currently available in the literature show that β3-ARs are upregulated in a hypoxic environment in several tissues and that their activation triggers a downstream cascade that promotes pro-angiogenic, anti-inflammatory, and immunoregulating effects, as well as metabolic adaptative processes and chemoresistance to xenobiotics. These characteristics seem to be central in the development of the fetus. Conclusions: Available preclinical data suggest the possible role of β3-ARs in the pathogenesis of a large number of premature newborn pathologies. Since fetal growth takes place in a low oxygenated environment, preterm delivery exposes newborns to a relatively hyperoxic setting while their development is not fully completed. Given the β3-ARs upregulation in a hypoxic environment, premature exposure to higher oxygen concentration levels affects their expression and their activity, probably derailing fetal normal development and injuring several organs. β3-ARs might therefore represent a central element in the pathogenesis of some of the main pathologies that preterm babies often develop.