Reduced number of alveoli after birth in rats exposed to iron in utero.

Abstract

Background: Clinical studies have shown that diffuse chorioamniotic hemosiderosis (DCH) is a risk factor for bronchopulmonary dysplasia (BPD). However, the details of the underlying mechanism are unknown. We focused on iron, one of the blood components that diffuses within the amniotic cavity in DCH. Specifically, we conducted a histological evaluation of its effects on fetal lung development.

Methods: Iron dextran 10 mg (Fe group) or physiological saline (control group) was injected into the individual amniotic cavities of pregnant Sprague Dawley rats on gestational day 19. The pups were born naturally, and the placentas and lungs collected on postnatal days 1, 14, and 60 were subjected to histological analysis.

Results: The placenta and lungs of the Fe group on day 14 contained significantly larger numbers of iron-positive granules. Morphological analysis of the lungs showed that on day 60, the total number of alveoli was significantly lower in the Fe group (p = 0.015). Immunohistochemical staining of the lung tissue for 8-hydroxy-2'-deoxyguanosine showed that, on day 1, there were significantly more positive cells in the Fe group (p = 0.003). The number of ectodermal dysplasia 1 positive cells on day 14 was significantly increased in the Fe group (p = 0.001).

Conclusions: These results suggest that diffuse iron deposition in immature fetal lungs increases oxidative stress and decreases the number of postnatal alveoli associated with impaired lung development.