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Journal of Perinatal Medicine

Official Journal of the World Association of Perinatal Medicine

Editor-in-Chief: Dudenhausen, Joachim W.

Editorial Board Member: / Bancalari, Eduardo / Greenough, Anne / Genc, Mehmet R. / Chervenak, Frank A. / Chappelle, Joseph / Bergmann, Renate L. / Bernardes, J.F. / Bevilacqua, G. / Blickstein, Isaac / Cabero Roura, Luis / Carbonell-Estrany, Xavier / Carrera, Jose M. / D`Addario, Vincenzo / D'Alton, MD, Mary E. / Dimitrou, G. / Grunebaum, Amos / Hentschel, Roland / Köpcke, W. / Kawabata, Ichiro / Keirse, Marc J.N.C. / Kurjak M.D., Asim / Lee, Ben H. / Levene, Malcolm / Lockwood, Charles J. / Marsal, Karel / Makatsariya, Alexander / Nishida, Hiroshi / Ogata, Edward / Papp, Zoltán / Pejaver, Ranjan Kumar / Pooh, Ritsuko K. / Romero, Roberto / Saugstad, Ola D. / Schenker, Joseph G. / Sen, Cihat / Seri, Istvan / Vetter, Klaus / Winn, Hung N. / Young, Bruce K. / Zimmermann, Roland

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Perinatal exposure to di-(2-ethylhexyl) phthalate leads to restricted growth and delayed lung maturation in newborn rats

Shang-Qin Chen1, a / Jin-Ni Chen1, a / Xiao-Hong Cai1 / Guo-Rong Chen2 / Yuan Gao1 / Ren-Shan Ge3 / Hai-Shan Wu4 / Zhen-Lang Lin1 / Jing Lin1, 5

1Department of Pediatrics, Yuying Children's Hospital of Wenzhou Medical College, Wenzhou 325027, China

2Department of Pathology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China

3Population Council, The Rockefeller University, New York, NY 10021, USA

4Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA

5Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029-6574, USA

aBoth authors contribute equally to this work.

Corresponding author: Jing Lin Department of Pediatrics Mount Sinai School of Medicine One Gustave L. Levy Place Box 1508 New York NY 10029 USA

Citation Information: Journal of Perinatal Medicine. Volume 38, Issue 5, Pages 515–521, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: 10.1515/jpm.2010.083, July 2010

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Background: Pregnant women and infants have significant exposures to the most commonly used plasticizer di-(2-ethylhexyl) phthalate (DEHP).

Objectives: This study was designed to evaluate the effects of DEHP exposure on growth and lung maturation in rats and determine if DEHP regulation of 11β-hydroxysteroid dehydrogenase type 1 gene (Hsd11b1) expression in the lung tissue plays a role in its effects on lung maturation.

Method: Pregnant Sprague-Dawley rats were treated from gestational day 12 to postnatal day (PND) 21 with DEHP orally at dosages of 0, 10, 100 or 750 mg/kg/day, respectively (n=8 for each group). Two rat pups (one male and one female) from each litter were sacrificed at PND 1 and 21. Body weight was measured and the lung was processed for histology and calculation of lung interstitial tissue proportion as well as real-time PCR determination of the expressions of Hsd11b1, surfactant associated protein-A1 gene (Sftpa1) and B gene (Sftpb).

Results: The perinatal DEHP exposure led to a dose dependent intrauterine and postnatal growth restriction (P<0.001). High dose DEHP (750 mg/kg/day) exposure led to decreased gas-exchange space as evidenced by increased lung interstitial tissue proportion (P<0.001), but did not cause significant changes in Hsd11b1, Sftpa1 or Sftpb gene expression in the rat lung at PND 1. The DEHP-induced change in lung histology remained significant at PND 21 with improvement despite continual exposure to DEHP.

Conclusion: Perinatal DEHP exposure leads to growth restriction and delayed lung maturation in newborn rats.

Keywords: 11β-hydroxysteroid dehydrogenase; DEHP; intrauterine growth restriction; lung maturation; newborn; phthalate; postnatal growth restriction; rat

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