Lung development in the fetus may be adversely affected by a mother’s gestational diabetes, based on data from in vivo, in vitro, and ex vivo studies.
Gestational diabetes mellitus (GDM) has recently been associated with fetal lung underdevelopment (FLUD) and delayed lung maturation that may lead to immediate respiratory distress in newborns and later chronic lung disease, Pengzheng Chen, PhD, of Shandong University, Jinan, China, and colleagues wrote.
Antenatal corticosteroids are considered an effective treatment for gestational fetal lung underdevelopment, but recent studies have shown adverse effects of these medications, and therefore more research is needed to identify the etiology and pathogenesis of FLUD induced by GDM, they said.
In a study published in the International Journal of Nanomedicine, the researchers collected umbilical cord blood samples from patients with GDM and matched controls at a single hospital in China.
“Using an ex vivo exosome exposure model of fetal lung explants, we observed the morphological alteration of lung explants and evaluated the expression of molecules involved in lung development,” the researchers wrote.
Fetal lung underdevelopment was more common after exposure to exosomes from the umbilical cord plasma of individuals with gestational diabetes mellitus, compared with exosomes from healthy controls.
The researchers also used mouse models to examine the effects of exosomes on fetal lung development in vivo. They found that exosomes associated with GDM impeded the growth, branching morphogenesis, and maturation of fetal lungs in mouse models. In addition, the expression of the apoptotic biomarkers known as BAX, BIM, and cleaved CASPASE-3 was up-regulated in GDMUB-exosomes and HG-exos groups, but the antiapoptotic protein BCL-2 was down-regulated; this further supported the negative impact of GDM exomes on fetal lung development, the researchers said.
The researchers then conducted miRNA sequencing, which showed that the miRNA in placenta-derived exosomes from GDM pregnancies were distinct from the miRNA in exosomes from healthy control pregnancies.
The study findings were limited by several factors including the impurity of the isolated placenta-derived exosomes from the umbilical cord blood plasma, which were not placenta specific, the researchers noted. Other limitations included the lack of data on different stages of lung development, and more research is needed to validate miRNAs and to explore the signally pathways involved in fetal lung development.
However, the study is the first known to demonstrate an adverse effect of GDM on fetal lung development via in vitro, ex vivo, and in vitro models, they said.
“These data highlight an emerging role of placenta-derived exosomes in the pathogenesis of fetal lung underdevelopment in GDM pregnancies, and provide a novel strategy for maternal-fetal communication,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.