US EPA

1597628 

Journal Article 

In utero phthalate effects in the female rat: A model for MRKH syndrome 

Hannas, BR; Howdeshell, KL; Furr, J; Earl Gray, L, Jr 

2013 

1 

Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 

223 

3 

315-321 

English 

23542816 

10.1016/j.toxlet.2013.03.021 

WOS:000327492900009 

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 GD8 to 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. 

Reproductive malformations; Uterine; Critical period