title: Programming effects of short prenatal exposure to cortisol.
abstract: Recent studies have linked fetal exposure to a suboptimal intrauterine environment with adult hypertension. The aims of this study were twofold: 1) to see whether cortisol treatment administered to the ewe for 2 days at 27 days of gestation (term approximately 150 days) resulted in high blood pressure in offspring; 2) to study the effect of the same treatment on gene expression in the brain at 130 days of gestation and in lambs at 2 months of age. Mean arterial pressure was significantly higher in the adult female and male offspring of sheep treated with cortisol than in the control group (females: 89+/-2 mmHg vs. 81+/-2; P<0.05 and males: 102+/-4 mmHg vs. 91+/-3; P<0.05). Prenatal cortisol treatment led to up-regulation of angiotensinogen, AT1, MR, and GR mRNA in the hippocampus in fetuses at 130 days of gestation but not in the animals at 2 months of age. This is the first evidence that short prenatal exposure to cortisol programmed high blood pressure in the adult female and male offspring of sheep. Altered gene expression in the hippocampus could have a significant effect on the development of the hippocampus, and on postnatal behavior.
authors.affiliation: Howard Florey Institute, University of Melbourne, Parkville 3010, Melbourne, Victoria, Australia. m.dodic@hfi.unimelb.edu.au
authors.forename: Miodrag
authors.initials: M
authors.lastname: Dodic
authors.forename: Vicky
authors.initials: V
authors.lastname: Hantzis
authors.forename: Jhodie
authors.initials: J
authors.lastname: Duncan
authors.forename: Sandra
authors.initials: S
authors.lastname: Rees
authors.forename: Irene
authors.initials: I
authors.lastname: Koukoulas
authors.forename: Kelli
authors.initials: K
authors.lastname: Johnson
authors.forename: E Marelyn
authors.initials: EM
authors.lastname: Wintour
authors.forename: Karen
authors.initials: K
authors.lastname: Moritz
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D005865:Gestational Age; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D012084:Renin-Angiotensin System / Q000187:drug effects; D012756:Sheep; D013997:Time Factors; D015533:Transcriptional Activation
chemical_list: D012333:RNA, Messenger; D006854:Hydrocortisone