title: [Effects of di-(2-ethylhexyl) phthalate exposure on reproductive development and PPARs in prepubertal female rats].
abstract: OBJECTIVE
  To investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure on pubertal development and reproductive endocrine function in prepubertal female rats and its possible mechanisms.
  
  
  METHODS
  40 female SD rats at 3-week-old were randomly divided into a control group (corn oil) and three exposure groups, which were exposed consecutively for 28 days to DEHP by oral gavage at doses of 50, 150 and 500 mg/(kg x d). The onset of puberty was determined by daily examination for vaginal opening (OV), breast development and the first estrous cycle. By the end of the experiment, the rats were sacrificed during the diestrous stage. The gene expression interrelated with ovary function was detected by real-time PCR. Serum levels of follicle stimulating hormone (FSH) luteinizing hormone (LH), estradiol (E2), progesterone (P4) and testosterone (T) were measured by ELISA. The morphological change of ovaries was observed by HE staining under optical microscope. The expression of PPARgamma protein in ovary cells was measured by immuohistochemistry.
  
  
  RESULTS
  The age of vaginal opening was advanced by DEHP exposure in 500 mg/kg group, and the body weight was increased at the time of vaginal opening in 150 and 500 mg/kg groups (P < 0.05). Compared to the control group, the level of T in all DEHP groups was decreased; the levels of FSH and E2 were decreased and the level of P4 was increased in 150 and 500 mg/kg groups (P < 0.05). The gene expression of P4S0Aromin 150 and 500 mg/kg groups was significantly decreased compared to the control group. A significant increase of atretic follicles and a significant reduction of corpora lutea were observed in 150 and 500 mg/kg groups compared to the control group. The expression of PPARgamma protein in granulosa cells of follicle and corpora lutea in 150 and 500 mg/kg groups was higher than that in the control group and 50 mg/kg group (P < 0.05).
  
  
  CONCLUSIONS
  DEHP exposure can affect the pubertal development and reproductive endocrine function in prepubertal female rats, and its possible mechanism may be correlated with PPARgamma.
authors.affiliation: Department of Toxicology, Shenyang Medical College, Key Laboratory of Environmental Pollutants and Microecosystem of Liaoning Province, Shenyang 110034, China. mymacmu@yahoo.com
authors.forename: Mingyue
authors.initials: M
authors.lastname: Ma
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiucong
authors.initials: X
authors.lastname: Pei
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D010053:Ovary / Q000254:growth & development / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010968:Plasticizers / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D012741:Sexual Maturation / Q000187:drug effects* / Q000502:physiology
chemical_list: D052244:Endocrine Disruptors; D012739:Gonadal Steroid Hormones; D047495:PPAR gamma; D010968:Plasticizers; D004051:Diethylhexyl Phthalate