Igf2 deficiency results in delayed lung development at the end of gestation.
IGF-II is a polypeptide hormone with structural homology to insulin and IGF-I. IGF-II plays an important role in fetal growth as mice with targeted disruption of the IGF-II gene (Igf2) exhibit severe growth retardation. The role of IGFs in the fetal lung has been suggested by several studies, including those that have identified IGF mRNA expression, and that of their receptors and binding proteins in the lungs at different stages of development. In this study, we used mice carrying a null mutation of Igf2 (Igf2-/- mice) to determine whether the absence of IGF-II had any effect in fetal lung maturation. Our results showed that the lungs of Igf2-/- fetuses had thicker alveolar septae and poorly organized alveoli when compared with those of Igf2+/+ on d 17.5 and 18.5 of gestation. These morphological alterations may be the result of exposure to lower levels of glucocorticoids because plasma corticosterone levels were significantly lower in Igf2-/- mothers compared with wild-type controls. In support of this, fetuses from homozygous knockout matings, where mothers were treated with 15 microg/ml corticosterone, and Igf2-/- fetuses obtained from heterozygous matings had similar lung histology to those of wild-type fetuses. Finally, we found that IGF-I and SP-B mRNA levels were up-regulated in the lungs of Igf2-/- fetuses at the end of gestation. This study suggests that Igf2 plays an important role in the development of the fetal lung and may affect fetal lung maturation by regulating maternal factors, such as corticosterone levels, during pregnancy.
Silva
Delia
D
Division of Endocrinology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Karp Research Building 04212, Boston, Massachusetts 02115, USA.
Venihaki
Maria
M
Guo
Wei-Hui
WH
Lopez
Mary Frances
MF
D000818:Animals; D049109:Cell Proliferation; D003345:Corticosterone / Q000032:analysis / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D047109:Fetal Development / Q000235:genetics; D005325:Fetal Organ Maturity / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008168:Lung / Q000196:embryology*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis / Q000235:genetics*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011663:Pulmonary Surfactants / Q000378:metabolism
D011663:Pulmonary Surfactants; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003345:Corticosterone