title: Preeclampsia induced by cadmium in rats is related to abnormal local glucocorticoid synthesis in placenta.
abstract: BACKGROUND
  Cadmium (Cd) is a major environmental pollutant that causes multiple adverse health effects in humans and animals. In this study, we investigated Cd-mediated toxic effects in rats during pregnancy and endocrine intervention in the placenta.
  
  
  METHODS
  We exposed pregnant rats to intraperitoneal Cd (CdCl2) at various doses (0, 0.25, and 0.5 mg/kg BW/day) from days 5 to 19 of pregnancy and evaluated the maternal-placental-fetal parameters linked to preeclampsia. We measured the corticosterone level in rat serum and placental tissue by sensitive ELISA and also analyzed the expression of glucocorticoid synthesis enzymes in the placenta.
  
  
  RESULTS
  Key features of preeclampsia (PE), including hypertension, proteinuria, glomerular endotheliosis, placental abnormalities and small fetal size, appeared in pregnant rats after injection with 0.5 mg/kg BW/day Cd. The placental corticosterone production and maternal and fetal plasma corticosterone levels were increased in rats treated with 0.5 mg/kg BW/day Cd (P <0.01). The expression of 21-hydroxylase (CYP21) and 11beta-hydroxylase (CYP11B1), enzymes essential for corticosteroid synthesis, were increased in Cd-exposed placenta (P <0.01). 11beta-hydroxysteroid dehydrogenase (11beta-HSD2), a dominant negative regulator of local glucocorticoid levels, was decreased in Cd-exposed placenta (P <0.01).
  
  
  CONCLUSIONS
  Our study demonstrates for the first time that changes in placental glucocorticoid synthesis induced by Cd exposure during pregnancy could contribute to preeclamptic conditions in rats.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.forename: Shunqun
authors.initials: S
authors.lastname: Luo
authors.forename: Duyun
authors.initials: D
authors.lastname: Ye
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Sisi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. yphuangp@126.com.
authors.forename: Yinping
authors.initials: Y
authors.lastname: Huang
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D002105:Cadmium Poisoning / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D004794:Enzyme Repression / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000097:blood / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis; D013255:Steroid 21-Hydroxylase / Q000096:biosynthesis; D014018:Tissue Distribution; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D004785:Environmental Pollutants; D005938:Glucocorticoids; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C531512:Cyp21a1 protein, rat; D013255:Steroid 21-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D019256:Cadmium Chloride; D003345:Corticosterone
references.citation: Toxicol Lett. 2009 Aug 10;188(3):186-91
references.pmid: 19379801
references.citation: Reprod Toxicol. 2012 Dec;34(4):622-7
references.pmid: 23017269
references.citation: J Steroid Biochem Mol Biol. 2013 Sep;137:176-82
references.pmid: 23770321
references.citation: Mol Cell Biochem. 2004 Jan;255(1-2):87-92
references.pmid: 14971649
references.citation: Endocrinology. 2014 Jan;155(1):299-309
references.pmid: 24169559
references.citation: Hypertension. 2013 Dec;62(6):1046-54
references.pmid: 24060885
references.citation: Andrologia. 2012 May;44 Suppl 1:813-22
references.pmid: 21933223
references.citation: Environ Health Perspect. 2012 Feb;120(2):284-9
references.pmid: 21862444
references.citation: J Toxicol Environ Health B Crit Rev. 2012;15(5):348-63
references.pmid: 22852814
references.citation: Toxicology. 2009 Mar 4;257(1-2):64-9
references.pmid: 19126424
references.citation: Med Princ Pract. 2013;22 Suppl 1:8-19
references.pmid: 23949305
references.citation: Endocr Rev. 2004 Dec;25(6):947-70
references.pmid: 15583024
references.citation: Exp Biol Med (Maywood). 2004 May;229(5):383-92
references.pmid: 15096650
references.citation: Toxicol Ind Health. 2009 Aug;25(7):447-53
references.pmid: 19648216
references.citation: Int Arch Occup Environ Health. 2002 Oct;75 Suppl:S36-44
references.pmid: 12397409
references.citation: Placenta. 2005 Apr;26(4):273-81
references.pmid: 15823613
references.citation: Am J Physiol Endocrinol Metab. 2011 Jul;301(1):E11-24
references.pmid: 21540450
references.citation: Mol Cell Endocrinol. 2004 Dec 30;228(1-2):103-19
references.pmid: 15541575
references.citation: Pediatr Res. 2009 Feb;65(2):198-202
references.pmid: 19047954
references.citation: Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E135-E142
references.pmid: 16144812
references.citation: Med Arch. 2013;67(5):339-41
references.pmid: 24601166
references.citation: Acta Biochim Pol. 2012;59(4):475-82
references.pmid: 23240106
references.citation: Biol Reprod. 2009 Jun;80(6):1209-15
references.pmid: 19208548
references.citation: J Mol Biol. 1999 Jun 11;289(3):603-17
references.pmid: 10356332
references.citation: Biometals. 2010 Oct;23(5):769-82
references.pmid: 20517707
references.citation: Med Hypotheses. 2011 Aug;77(2):188-91
references.pmid: 21550175
references.citation: Met Ions Life Sci. 2013;11:415-90
references.pmid: 23430781
references.citation: Environ Sci. 2006;13(2):107-16
references.pmid: 16788562
references.citation: Toxicology. 2006 Oct 3;227(1-2):15-20
references.pmid: 16938374
references.citation: Can J Biochem Physiol. 1961 Feb;39:203-14
references.pmid: 13774343