title: Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring.
abstract: Maternal treatment with the synthetic glucocorticoid, dexamethasone has been reported to result in a nephron deficit and development of hypertension in the offspring of rats. However, it is not known whether elevated maternal corticosterone (CORT), the natural glucocorticoid, has similar effects on blood pressure and nephron endowment. The present study investigated the effects of CORT (0.8 mg kg(-1) day(-1)) administration on embryonic day 14 (E14) and E15 of pregnancy on: (1) nephron number at postnatal day 30 (PN30); (2) blood pressure at PN120; and (3) receptors of the renal renin-angiotensin system (RRAS) (AT(1)Ra, AT(1)Rb and AT(2)Ra) during both embryonic (E16, E20) and adolescent (PN30) life. Plasma CORT concentrations were approximately doubled 30 min after injection. Unbiased stereological analysis revealed that maternal CORT treatment resulted in a nephron deficit of 21 and 19% in male and female offspring, respectively. Mean arterial pressures were significantly elevated in offspring of both sexes from the CORT group. Real-time PCR revealed that CORT treatment increased expression of AT(1)Ra and AT(2)R at E16, and at PN30. Expression of AT(1)Rb was downregulated in embryonic life but upregulated at PN30. We believe that these results are the first to demonstrate that maternal CORT treatment results in a nephron deficit and development of hypertension in the rat offspring. Changes in the RRAS may be contributing to these phenotypes. Critically, this study suggests that increased but physiological levels of the natural glucocorticoid can programme similar changes to those seen with pharmacological doses of the synthetic glucocorticoid. This may have important implications for women experiencing significant stress during pregnancy.
authors.affiliation: Department of Anatomy and Cell Biology, Monash University, Clayton, 3800, Australia.
authors.forename: Reetu R
authors.initials: RR
authors.lastname: Singh
authors.forename: Luise A
authors.initials: LA
authors.lastname: Cullen-McEwen
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kett
authors.forename: Wee-Ming
authors.initials: WM
authors.lastname: Boon
authors.forename: John
authors.initials: J
authors.lastname: Dowling
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
authors.forename: Karen M
authors.initials: KM
authors.lastname: Moritz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009399:Nephrons / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000502:physiology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012083:Renin; D003345:Corticosterone