title: Exposure to di(2-ethylhexyl) phthalate inhibits luteal function via dysregulation of CD31 and prostaglandin F2alpha in pregnant mice.
abstract: BACKGROUND
  Di(2-ethylhexyl) phthalate (DEHP) exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, whether it is associated with the alteration of luteal function remains unknown. Thus, our aim in this study was to explore the effect and mechanism of DEHP on luteal function in pregnant mice in vivo.
  
  
  METHODS
  Mice were administered DEHP by gavage at 125, 250, 500 mg/kg/day from gestational days (GD) 1 to 9 or 13. Levels of serum progesterone and estradiol were measured by radioimmunoassay. The numbers and sizes of corpora lutea were calculated by ovarian histomorphology. Steroidogenic enzymes were assessed by qRT-PCR. CD31 protein was detected by immunocytochemistry, and prostaglandin F2alpha (PGF2alpha) levels were evaluated by enzyme immunoassay.
  
  
  RESULTS
  Treatment with DEHP significantly inhibited progesterone secretion in pregnant mice in a dose-dependent manner but did not inhibit estradiol production on GD 9 and 13. Treatment also showed concomitant decreases in transcript levels for key steroidogenic enzymes (CYP11A, 3β-HSD, and StAR) on GD 13. Furthermore, DEHP administration significantly reduced the numbers and sizes of corpora lutea on GD 13. No significant changes in the ratio of ovary weight vs. body weight were observed between the control group and treated animals on GD 9 and 13. In addition, treatment with DEHP significantly inhibited CD31 expression of corpora lutea, whereas plasma PGF2alpha levels in DEHP treatment groups were significantly higher compared with the control groups on GD 9 and 13.
  
  
  CONCLUSIONS
  The results show DEHP significantly inhibits luteal function of pregnant mice in vivo, with a mechanism that seems to involve the down-regulation of progesterone and steroidogenic enzymes message RNA, the decrease in CD31 expression, and the increase in PGF2alpha secretion.
authors.affiliation: Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China. 741046571@qq.com.
authors.forename: Meijun
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China. 1037715496@qq.com.
authors.forename: Lidan
authors.initials: L
authors.lastname: Lai
authors.affiliation: Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China. 258056615@qq.com.
authors.forename: Teng
authors.initials: T
authors.lastname: Zong
authors.affiliation: Department of Obstetrics and Gynecology, Hospital of Jixi Province People, Nanchang, Jiangxi, China. lingyan1205@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China. yangbei@ncu.edu.cn.
authors.forename: Bei
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China. 13393733537@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China. 544182657@qq.com.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, China. kuanghaibin@ncu.edu.cn.
authors.forename: Haibin
authors.initials: H
authors.lastname: Kuang
mesh_terms: D000818:Animals; D003338:Corpus Luteum / Q000033:anatomy & histology / Q000187:drug effects; D003340:Corpus Luteum Maintenance / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D015237:Dinoprost / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009929:Organ Size; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011374:Progesterone; D004958:Estradiol; D015237:Dinoprost; D004051:Diethylhexyl Phthalate