DEHP effects on histology and cell proliferation in lung of newborn rats

Abstract

Di-(2-ethylhexyl)-phthalate (DEHP), the plasticizer employed in the fabrication of polyvinyl chloride, is known to be released by many medical devices, namely endotracheal tubes currently utilised for pulmonary ventilation of pre-term newborns. When experimentally administered, especially to rodents, the phthalate reportedly causes alterations to several tissues, immature animals being even more responsive targets than adult ones. In the present research, female rats were fed with DEHP in the last week of pregnancy and after delivery, and lung of their pups was morphologically and immunohistochemically analysed. We detected significant alveolar simplification (larger but fewer alveoli with decreased septation), with consequent sensible reduction of gas-exchange surface, at several stages of postnatal development, in distal lung parenchyma of DEHP-treated rats. Moreover, the quantification of PCNA-expressing cells demonstrates that in treated pups the proliferation rates of epithelial and mesenchymal cells progressively increased during the first two postnatal weeks, at difference with controls animals, where the highest proliferation levels were reached at postnatal day 7. The obtained results strongly support the hypothesis that DEHP profoundly affects the alveolarization process in mammalian lung.