Boston Combined Residency Program, Boston Children's Hospital, Boston, Massachusetts.
University of Colorado School of Medicine, Aurora, Colorado.
Am J Physiol Lung Cell Mol Physiol. 2022 Dec 1;323(6):L651-L658. doi: 10.1152/ajplung.00204.2022. Epub 2022 Oct 11.
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.
支气管肺发育不良（BPD）与绒毛膜羊膜炎（CA）和妊娠高血压疾病（HDP）等围产期疾病的相关性已得到越来越多的认识。然而，这些产前疾病导致 BPD 风险增加的机制尚未得到很好的描述。本综述的目的是讨论胎盘在 BPD 易感性中的作用，作为导致胎儿肺部发育不良的宫内改变的主要驱动因素。我们假设，由于结构和功能上的相似性，妊娠期间的胎盘疾病可以特异性地影响发育中的胎儿肺部，从而形成独特的胎盘-肺部连接。在本综述中，我们通过分析评估 BPD 易感性的临床文献和临床前模型系统，探讨了这一假说，讨论了 BPD 表型，并概述了将胎盘研究纳入胎儿肺部发育研究的策略。我们还讨论了从产前类固醇对胎儿肺部发育的调节作用研究中获得的重要概念。最后，我们提出，选择合适的动物模型和建立包含人胎盘成分的体外肺发育模型系统，对于继续了解和解决产前 BPD 易感性问题至关重要。
