Placental expression of insulin-like growth factor receptor-1 and insulin receptor in the growth-restricted fetal rat

Abstract

Objective: The type 1 insulin-like growth factor receptor (IGF-R1), which resembles the insulin receptor (INS-R), is expressed abundantly in the placenta. The regulation of fetal growth by IGFs and insulin might reflect their actions on the placenta. This study compared the placental expression of IGF-R1 and INS-R in growth-restricted and normal pregnancies.

Methods: Fetal growth restriction was produced in Sprague-Dawley rats by bilateral ligation of the uterine artery on day 19 (term = 21.5 days). Fetuses were delivered by hysterotomy on day 20, and placental samples were frozen. Fetuses that had been subjected to a sham operation of maternal laparotomy without uterine artery manipulation were studied as matched controls. IGF-R1 and INS-R message was assessed by reverse transcription and polymerase chain reaction amplification of extracted placental RNA. The receptors also were assessed by Western blotting of extracted placental protein. Measurements for the growth-restricted group were expressed as a multiple of that of the matched sham litter.

Results: Placental IGF-R1 messenger RNA (mRNA) level was significantly lower in the growth-restricted fetuses (0.66 x sham [0.47-0.93], P <.05), but INS-R mRNA was not different (0.89 x sham [0.63-1.3], P >.5). IGF-R1 protein transcript was similarly reduced in the growth-restricted fetuses (0.78 x sham [0.69-0.88], P <.005), but the INS-R protein transcript was not (0.98 x sham [0.69-1.4], P >.8). Birth weights were significantly less in the growth-restricted group (3.06 +/- 0.07 versus 3.29 +/- 0.06 g, P =.016); placental weights were not (0.54 +/- 0.02 versus 0.54 +/- 0.02 g, P =.90).

Conclusions: The placenta responds to decreased nutrient delivery with decreased expression of IGF-R1. This would reduce the growth-promoting effects of insulin-like growth factors, which include augmentation of placental lactogen production and glucose and amino acid transport. INS-R was unaffected, which suggests that placental response to insulin is less important than its response to insulin-like growth factors in growth restriction.