title: Growth restriction in the rat alters expression of cardiac JAK/STAT genes in a sex-specific manner.
abstract: Uteroplacental insufficiency resulting in intrauterine growth restriction has been associated with the development of cardiovascular disease, coronary heart disease and increased blood pressure, particularly in males. The molecular mechanisms that result in the programming of these phenotypes are not clear. This study investigated the expression of cardiac JAK/STAT signalling genes in growth restricted offspring born small due to uteroplacental insufficiency. Bilateral uterine vessel ligation was performed on day 18 of pregnancy to induce growth restriction (Restricted) or sham surgery (Control). Cardiac tissue at embryonic day (E) 20, postnatal day (PN) 1, PN7 and PN35 in male and female Wistar (WKY) rats (n=7-10 per group per age) was isolated and mRNA extracted. In the heart, there was an effect of age for males for all genes examined there was a decrease in expression after PN1. With females, JAK2 expression was significantly reduced after E20, while PI3K in females was increased at E30 and PN35. Further, mRNA expression was significantly altered in JAK/STAT signalling targets in Restricteds in a sex-specific manner. Compared with Controls, in males, JAK2 and STAT3 were significantly reduced in the Restricted, while in females SOCS3 was significantly increased and PI3K significantly decreased in the Restricted offspring. Finally, there were specific differences in the levels of gene expression within the JAK/STAT pathway when comparing males to females. Thus, growth restriction alters specific targets in the JAK/STAT signalling pathway, with altered JAK2 and STAT3 potentially contributing to the increased risk of cardiovascular disease in the growth restricted males.
authors: 1Department of Physiology,The University of Melbourne,Parkville,VIC,Australia.
authors: S
authors: S
authors: van der Linde
authors: 2Department of Human Biosciences,Latrobe University,Bundoora,VIC,Australia.
authors: T
authors: T
authors: Romano
authors: 3Centre for Physical Activity and Nutrition Research,Deakin University,Burwood,VIC,Australia.
authors: G
authors: G
authors: Wadley
authors: 1Department of Physiology,The University of Melbourne,Parkville,VIC,Australia.
authors: A J
authors: AJ
authors: Jeffries
authors: 1Department of Physiology,The University of Melbourne,Parkville,VIC,Australia.
authors: M E
authors: ME
authors: Wlodek
authors: 1Department of Physiology,The University of Melbourne,Parkville,VIC,Australia.
authors: D H
authors: DH
authors: Hryciw
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010927:Placental Insufficiency / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019869:Phosphatidylinositol 3-Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2