Effects of intrafetal IGF-I on growth of cardiac myocytes in late-gestation fetal sheep

1 Department of Physiology and Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney; and 2 Discipline of Obstetrics and Gynecology, School of Pediatrics and Reproductive Health, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia Submitted 7 June 2008 ; accepted in final form 4 January 2009 Intrafetal insulin-like growth factor (IGF)-I promotes cardiac hypertrophy in the late-gestation fetal sheep; whether these effects are sustained is unknown. IGF-I was infused for 4 days at 80 µg/h from 121 to 125 days of gestation, and its effects at 128 days, 3 days after the infusion stopped, were determined by comparison with untreated fetal sheep. After IGF-I treatment, fetal weights were similar to those in control fetuses but kidney weights were bigger ( P < 0.05), as were spleen weights of male fetuses ( P < 0.05). Cardiac myocytes were larger in female than male fetal sheep ( P < 0.001). IGF-I increased male ( P < 0.001) but not female myocyte volumes. IGF-I did not alter the proportions of uni- or binucleated right or left ventricular myocytes. Female fetal sheep had a greater proportion of binucleated cardiac myocytes than males ( P < 0.05). IGF-I-treated fetuses had a slightly greater proportion of right ventricular nuclei in cell cycle phase G 2 /M and a reduced proportion of G 0 /G 1 phase nuclei ( P < 0.1). Therefore, evidence for IGF-I-stimulated cardiac cell hyperplasia in fetal sheep in late gestation was limited. In conclusion, the greater sizes and larger proportion of binucleated cardiac myocytes in female fetal sheep suggest that myocyte maturation may occur earlier in females than in males. This may explain in part the male sex-specific responsiveness of cardiac hypertrophy to IGF-I in late gestation. If IGF-I-stimulated cardiomyocyte growth is accompanied by maturation of contractile function, IGF-I may be a potential therapeutic agent for maintaining cardiac output in preterm males. insulin-like growth factor-I; hypertrophy; sex; heart Address for reprint requests and other correspondence: E. R. Lumbers, Dept. of Physiology and Pharmacology, School of Medical Sciences, Univ. of New South Wales, Sydney, Australia 2052 (e-mail: e.lumbers{at}unsw.edu.au )