Effects of intrafetal IGF-I on growth of cardiac myocytes in late-gestation fetal sheep.
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 microg/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.
Lumbers
Eugenie R
ER
Department of Physiology, University of New South Wales, Sydney, Australia. e.lumbers@unsw.edu.au
Kim
Min Young
MY
Burrell
Judith H
JH
Kumarasamy
Vasumathy
V
Boyce
Amanda C
AC
Gibson
Karen J
KJ
Gatford
Kathryn L
KL
Owens
Julie A
JA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006321:Heart / Q000033:anatomy & histology* / Q000196:embryology*; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D012727:Sex Characteristics; D012756:Sheep; D013154:Spleen / Q000033:anatomy & histology / Q000196:embryology
D002245:Carbon Dioxide; D007334:Insulin-Like Growth Factor I; D010100:Oxygen