title: In utero phthalate effects in the female rat: a model for MRKH syndrome.
abstract: 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.
authors.affiliation: Reproductive Toxicology Branch, Toxicology Assessment Division, National Health and Environmental Effects Research Laboratories, Office of Research and Development, US EPA, Research Triangle Park, NC, United States. Electronic address: Hannas.bethany@epa.gov.
authors.forename: Bethany R
authors.initials: BR
authors.lastname: Hannas
authors.forename: Kembra L
authors.initials: KL
authors.lastname: Howdeshell
authors.forename: Johnathan
authors.initials: J
authors.lastname: Furr
authors.forename: L Earl
authors.initials: LE
authors.lastname: Gray
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000139:chemically induced*; D000818:Animals; D000831:Animals, Newborn; D000013:Congenital Abnormalities; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005836:Genitalia, Female / Q000002:abnormalities / Q000187:drug effects*; D005837:Genitalia, Male / Q000002:abnormalities / Q000187:drug effects; D005865:Gestational Age; D008297:Male; D009095:Mullerian Ducts / Q000002:abnormalities*; D038081:Organogenesis / Q000187:drug effects; D010795:Phthalic Acids / Q000008:administration & dosage / Q000633:toxicity*; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
chemical_list: D052244:Endocrine Disruptors; D010795:Phthalic Acids; D010968:Plasticizers
keywords: Critical period; Reproductive malformations; Uterine
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