Abstract:
Fetal growth restriction (FGR) is associated with decreased insulin secretory capacity and decreased insulin sensitivity in muscle in adulthood. We investigated whether intra-amniotic IGF-I treatment in late gestation mitigated the adverse effects of FGR on the endocrine pancreas and skeletal muscle at 18-months of age. Singleton-bearing ewes underwent uterine artery embolization between 103-107 days' gestational age, followed by five once-weekly intra-amniotic injections of 360 µg IGF-I (FGRI) or saline (FGRS), and were compared to an un-manipulated control group (CON). We measured offspring pancreatic endocrine cell mass and pancreatic and skeletal muscle mRNA expression at 18-months of age (n=7-9/sex/group). Total α-cell mass was increased ~225% in FGRI males vs. CON and FGRS males, while β-cell mass was not different between groups of either sex. Pancreatic mitochondria-related mRNA expression was increased in FGRS females vs. CON (NRF1, MTATP6, UCP2), and FGRS males vs. CON (TFAM, NRF1, UCP2), but was largely unchanged in FGRI males vs. CON. In skeletal muscle, mitochondria-related mRNA expression was decreased in FGRS females vs. CON (PPARGC1A, TFAM, NRF1, UCP2, MTATP6), FGRS males vs. CON (NRF1 and UCP2), and FGRI females vs. CON (TFAM and UCP2), with only MTATP6 expression decreased in FGRI males vs. CON. Although the window during which IGF-I treatment was delivered was limited to the final five weeks of gestation, IGF-I therapy of FGR altered the endocrine pancreas and skeletal muscle in a sex-specific manner in young adulthood.
