PhD Scientific Days 2022

Translational Medicine II. (Poster discussion will take place in the Aula during the Coffee Break)

Role of the Fetal Breathing Movements and the Pulmonary Lymphatics in Preparation of the Fetal Lung for Extrauterin Life

Text of the abstract

It has been shown recently that lymphatics, in addition to the surfactants, play an important role in the preparation of the fetal lung for neonatal respiration. However, the exact mechanisms have not been identified. It is known that the fetus performs periodic fetal breathing movements, but it is unclear whether they help the fetus breathing after birth.

We aimed to study the lungs of genetically modified mice lacking fetal breathing movements and of others previously injected with caffeine thus stimulated their fetal breathing movements.

In our first experiments, control and Clp1K/K mice were examined. Progressive loss of neural innervation develops in the skeletal muscles in the late fetal period of these genetically modified mice therefore fetal breathing movements do not develop. In contrast to other models, the early development of the skeletal system remains intact. In parallel, wild-type pregnant mothers were treated with a control solution or 20 mg/kg caffeine to stimulate fetal breathing movements. Lungs of embryos and neonates were sampled and paraffin-based histology was performed afterwards. The sections were stained with H&E or lymphatic-specific fluorescence-linked antibodies.

ClpK/K mouse neonates were cyanotic immediately after birth then died of respiratory failure. Based on histological examinations, we did not see any significant difference in the development of the lungs in the case of lack of fetal respiratory movements. However, there were some histological differences: the wall of the alveoli thickened, and the alveolar space narrowed. Additionally, normal lymphatics developed, which dilated markedly, but no molecular differences were seen. Currently, we are studying the viability of preterm mice and the histology of lung of embryos after stimulation of the fetal breathing movements with caffeine.

Collectively, the results suggest that fetal respiratory movements, in conjunction with pulmonary lymphatics, play an important role in the preparation of the fetal lung for respiration after birth. Our data suggest that stimulation of fetal respiratory movements may reduce the likelihood of developing respiratory failure in neonates.
Funding: K 139165, TKP2021-EGA-29, TKP2021-EGA-24, VEKOP-2.3.2-16-2016-00002, EFOP-3.6.3-VEKOP-16-2017-00009, VEKOP-2.3.3-15-2016-00006, Scientific and Innovative Research Fund of the Semmelweis University