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Prenatal Exposure to Nitrofen Induces Fryns Phenotype in Mice

Acosta, Juan M. MD; Chai, Yang DDS, PhD; Meara, John G. MD, DMD; Bringas, Pablo Jr BS; Anderson, Kathryn D. MD; Warburton, David DSc, MD

Original Articles

Prenatal exposure to nitrofen is known to cause multiple malformations in mice. The reported malformations include lung hypoplasia, diaphragmatic hernia, cardiovascular defects, skeletal malformations, cleft palate, and renal abnormalities. The authors present detailed findings of craniofacial defects after prenatal exposure to nitrofen, and propose that together with the previously reported malformations, nitrofen exposure induces a Fryns phenotype in mice. Fryns syndrome is a rare human genetic syndrome that is an autosomal recessive disorder characterized by lung hypoplasia, diaphragmatic hernia, craniofacial malformations, skeletal malformations, cardiovascular malformations, and genitourinary malformations. Timed-pregnant Swiss Webster mice were gavage-fed 25 mg of nitrofen on day 8 of gestation. Control animals received olive oil. Osteogenesis and chondrogenesis were studied in fetuses recovered on day 17 after Alcian blue-Alizarin red staining. Approximately 26% of the nitrofen-exposed embryos had severe craniofacial defects, and there was generalized delay in chondrogenesis and osteogenesis throughout the skeleton. No such defects were noted in the control group. The authors propose that prenatal exposure to nitrofen induces a Fryns phenotype in mice, and thus speculate that nitrofen may target similar molecular mechanisms to those that lead to Fryns syndrome.

*Division of Pediatric Surgery, Plastic Surgery, and Developmental Biology Program, Childrens Hospital Los Angeles Research Institute; and †The Center for Craniofacial Molecular Biology, University of Southern California, Keck School of Medicine and School of Dentistry, Los Angeles, CA.

Received Sep 6, 2000, and

in revised form Nov 9, 2000.

Accepted for publication Nov 9, 2000.

Address correspondence and reprint requests to Dr Warburton, Developmental Biology Program, Childrens Hospital Los Angeles Research Institute, 4650 Sunset Boulevard MS 35, Los Angeles, CA 90027.

Copyright © 2001 Wolters Kluwer Health, Inc. All rights reserved.