The Effect of Transplacental Administration of Glucagon-Like Peptide-1 on Fetal Lung Development in the Rabbit Model of Congenital Diaphragmatic Hernia.
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) increases surfactant protein expression in type 2 pneumocytes. Herein, we determine if transplacental GLP-1 treatment accelerates lung growth in the fetal rabbit model of congenital diaphragmatic hernia (DH).


METHODS
Time-mated does had an induction of DH on day 23 followed by daily GLP-1 or placebo injection until term. At that time, the does were weighed, fetal blood was obtained for GLP-1 assay, and the lungs were dissected. Fetal outcome measures were lung-to-body-weight ratio (LBWR), morphometry, and Ki67 and surfactant protein B (SPB) expression.


RESULTS
Maternal weight loss in the GLP-1 group was 7.1%. Fetal survival was lower in GLP-1 fetuses compared to placebo controls (27/85, 32% vs. 35/57, 61%; p < 0.05). Fetal GLP-1 levels were increased 3.6-fold. The LBWR of GLP-1 DH fetuses fell within the range of DH placebo fetuses (1.166 ± 0.207% vs. 1.312 ± 0.418%), being significantly lower than that of placebo-exposed unoperated fetuses (2.280 ± 0.522%; p < 0.001). GLP-1 did not improve airway morphometry. GLP-1 DH lungs had a reduced adventitial and medial thickness within the range of controls, and lesser muscularization of vessels measuring 30-60 µm. There were no differences in Ki67 and SPB expression.


CONCLUSIONS
GLP-1 at this dosage improves peripheric pulmonary vessel morphology in intra-acinar vessels with no effect on airway morphometry but with significant maternal and fetal side effects. Thus, it is an unlikely medical strategy.
Cluster Organ Systems, Department of Development and Regeneration, and Center for Surgical Technologies, Group Biomedical Sciences, KU Leuven, Leuven, Belgium.
Mary Patrice
MP
Eastwood
Anouck
A
Kampmeijer
Julio
J
Jimenez
Silvia
S
Zia
Rieta
R
Vanbree
Godelieve
G
Verbist
Jaan
J
Toelen
Jan A
JA
Deprest
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D047109:Fetal Development / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065630:Hernias, Diaphragmatic, Congenital; D019394:Ki-67 Antigen / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D011817:Rabbits; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D019394:Ki-67 Antigen; D037701:Pulmonary Surfactant-Associated Protein B; D052216:Glucagon-Like Peptide 1