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In utero phthalate effects in the female rat: a model for MRKH syndrome##
Citation:
Hannas, B., J. Furr, K. Howdeshell, AND E. Gray. In utero phthalate effects in the female rat: a model for MRKH syndrome##. TOXICOLOGY LETTERS. Elsevier Science Ltd, New York, NY, 223(3):315-21, (2013).
Impact/Purpose:
The purpose of the study was to describe a very novel and serious malformation of the female rat reproductive tract induced by prenatal exposure to a mixture of phthalates, which are ubiquitous in the environment. The phenotype provides a potentially very useful model to study the molecular and cellular biology of the induction of these malformations since a similar, poorly understood, syndrome exists in 1 in 5000 women who are born with these defects from unknown causes.
Description:
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phenomenon that is better studied in male offspring than females. The current study reports female reproductive tract malformations in the Sprague Dawley rat similar to those characteristic of MRKH syndrome, following in utero exposure to a mixture of 5 PEs. We determined that females are ~2-fold less sensitive to the effects of the 5-PE mixture than males for reproductive tract malformations. We were not fully successful in defining the critical exposure period for females; however, incidence of malformations was 88% following dosing from GD 8-19 versus 22% and 0% for GD8-13 and GD14-19, respectively. Overall, this study provides valuable information regarding female vulnerability to in utero phthalate exposure and further characterizes a potential model for the human MRKH syndrome.