Understanding the role of placental pathophysiology in the development of bronchopulmonary dysplasia

Am J Physiol Lung Cell Mol Physiol. 2022 Dec 1;323(6):L651-L658. doi: 10.1152/ajplung.00204.2022. Epub 2022 Oct 11.

Abstract

The associations between bronchopulmonary dysplasia (BPD) and the gestational pathologies of chorioamnionitis (CA) and hypertensive disorders of pregnancy (HDP) have become increasingly well recognized. However, the mechanisms through which these antenatal conditions cause increased risk of BPD remain less well characterized. The objective of this review is to discuss the role of the placenta in BPD predisposition as a primary driver of intrauterine alterations adversely impacting fetal lung development. We hypothesize that due to similarities in structure and function, placental disorders during pregnancy can uniquely impact the developing fetal lung, creating a unique placental-pulmonary connection. In the current review, we explore this hypothesis through analysis of clinical literature and preclinical model systems evaluating BPD predisposition, discussion of BPD phenotypes, and an overview on strategies to incorporate placental investigation into research on fetal lung development. We also discuss important concepts learned from research on antenatal steroids as a modulator fetal lung development. Finally, we propose that the appropriate selection of animal models and establishment of in vitro lung developmental model systems incorporating primary human placental components are key in continuing to understand and address antenatal predisposition to BPD.

Keywords: bronchopulmonary dysplasia; chorioamnionitis; fetal lung; placenta; preeclampsia.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchopulmonary Dysplasia* / pathology
  • Chorioamnionitis* / pathology
  • Female
  • Fetal Development
  • Humans
  • Infant, Newborn
  • Lung / pathology
  • Placenta / pathology
  • Pregnancy