Growth restriction before and after birth increases kinase signaling pathways in the adult rat heart

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Wadley, Glenn D, Wlodek, Mary E, Ng, Gwynth, Goodman, Craig ORCID: 0000-0002-5874-7743, Stathis, Christos ORCID: 0000-0003-0064-9523 and McConell, Glenn ORCID: 0000-0002-8572-9065 (2010) Growth restriction before and after birth increases kinase signaling pathways in the adult rat heart. Journal of Developmental Origins of Health and Disease, 1 (6). pp. 376-385. ISSN 2040-1744


To investigate the mechanisms for the previously reported development of adult cardiac hypertrophy in male rats following growth restriction, the levels of oxidative stress and activation of signaling kinases were measured in the left ventricle (LV) of adult rat offspring. In experiment one, bilateral uterine vessel ligation to induce uteroplacental insufficiency and growth restriction in the offspring (Restricted) or sham surgery was performed during pregnancy. Litters from sham mothers had litter size either reduced (Reduced Litter), which also restricted postnatal growth, or were left unaltered (Control). In males, Reduced Litter offspring had increased LV phosphorylation of AMPKα, p38 MAPK and Akt compared with Restricted and Controls (P < 0.05). In females, both Restricted and Reduced Litter adult offspring had increased LV phosphorylation of p38 MAPK and Akt, however, only Restricted offspring had increased phosphorylation of AMPKα (P < 0.05). In addition, only Restricted male offspring displayed LV oxidative stress (P < 0.05). Experiment two investigated in mothers exposed to uteroplacental insufficiency or sham surgery the effects of cross-fostering offspring at birth, and therefore the effects of the postnatal lactational environment. Surprisingly, the cross-fostering itself resulted in increased LV phosphorylation of AMPKα and Akt in females and increased phosphorylation of Akt in males compared with Control non-cross-fostered offspring (P < 0.05). In conclusion, kinase signaling in the adult LV can be programmed by uteroplacental insufficiency induced growth restriction in a gender-specific manner. In addition, the heart of adult rats is also sensitive to programming following the postnatal intervention of cross-fostering alone as well as by postnatal growth restriction.

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Item type Article
DOI 10.1017/S2040174410000607
Official URL
Subjects Historical > Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
Historical > FOR Classification > 1114 Paediatrics and Reproductive Medicine
Historical > SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Keywords ResPubID20949, development, cardiac muscle, kinases, foetal programming
Citations in Scopus 5 - View on Scopus
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