PhD Scientific Days 2022

Molecular Sciences V.

Reduced Prenatal Pulmonary Lymphatic Function Is Observed in ClpK/K Embryos With Impaired Motor Functions Including Fetal Breathing Movements in Preparation of the Developing Lung for Inflation at Birth

Text of the abstract

Introduction
Embryonic lungs must be inflated immediately after birth to establish respiration. In addition to pulmonary surfactant, recently we have revealed lymphatic function as a previously unknown mechanical regulator of prenatal lung compliance that prepares the embryonic lung for inflation at birth. Late gestation embryo performs episodic breathing-like movements called as fetal breathing movements (FBMs), but the physiological importance of these events is not clear.

Aims
In our current study we aimed to study the physiological role of FBMs in preparation for air inflation at birth.

Material and methods
Clp1K/K late gestation embryos develop a progressive loss of spinal motor neurons associated with axonal degeneration and denervation of neuromuscular junctions serving as an ideal genetic model to test the possible role of FBMs. Paraffin based histology was performed followed by HE and immunostaining against lung developmental and lymphatic markers.

Results
We demonstrated that Clp1K/K newborns show impaired motor function including FBMs and resulting in fatal respiratory failure after birth. Next, we showed that the alveolar septa are thicker, and the alveolar area is reduced in Clp1K/K late gestation embryos, while the expression of molecular markers of lung development are not affected. Importantly, pulmonary lymphatic vessels are dilated and the prenatal pulmonary lymphatic function is reduced in Clp1K/K late gestation embryos.

Conclusion
Our results have revealed that Clp1K/K embryos display reduced prenatal lymphatic function and impaired lung expansion. These findings suggest a possible mechanism that FBMs, stimulate prenatal lymphatic function in pulmonary collecting lymphatics lacking smooth muscle coverage to prepare the developing lung for inflation and gas exchange at birth. Moreover, these results raise the possibility that stimulating FBMs during late gestation might be an effective way to reduce the risk of the development of neonatal respiratory failure.

Funding
LP2014-4/2018 to ZJ, NVKP_16-2016-1-0039 to ZJ, VEKOP-2.3.2-16-2016-00002 and VEKOP-2.3.3-15-2016-00006 to ZJ and EFOP-3.6.3-VEKOP-16-2017-00009 to DS, GK, and GB, the Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Molecular Biology thematic program of the Semmelweis University to ZJ.