Perinatal exposure to di-(2-ethylhexyl) phthalate leads to restricted growth and delayed lung maturation in newborn rats.
Pregnant women and infants have significant exposures to the most commonly used plasticizer di-(2-ethylhexyl) phthalate (DEHP).



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



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).



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.



Perinatal DEHP exposure leads to growth restriction and delayed lung maturation in newborn rats.
Chen
Shang-Qin
SQ
Department of Pediatrics, Yuying Children's Hospital of Wenzhou Medical College, Wenzhou, China.
Chen
Jin-Ni
JN
Cai
Xiao-Hong
XH
Chen
Guo-Rong
GR
Gao
Yuan
Y
Ge
Ren-Shan
RS
Wu
Hai-Shan
HS
Lin
Zhen-Lang
ZL
Lin
Jing
J
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects
D017931:DNA Primers; D010968:Plasticizers; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D004051:Diethylhexyl Phthalate; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1