Altered placental structure induced by maternal food restriction in guineapigs: A role for circulating IGF-II and IGFBP-2 in the mother?

Maternal feed restriction may restrict fetal growth in part indirectly bq i mpairing placental functional development. Such actions could be mediated b y the insulin-like growth factors (IGF), which are important modulators of placental growth and differentiation and more generally, are influenced by nutrient availability. While a role for the fetal IGF axis has been demonst rated, less is known of the influence, if any, of that in the mother. This study. aimed to determine whether alterations in the maternal IGF axis and placental functional and structural development due to maternal food restri ction are related. We therefore examined the associations between placental structural parameters, the ratios of maternal to fetal plasma glucose and fetal to maternal plasma urea concentration, and maternal circulating IGF-I , IGF-II and IGFBP-2 in ad libitum fed and food restricted (70-90 per cent of the ad libitum intake) pregnant guinea pigs. In mid-gestation, fetal wei ght (r = 0.65, P = 0.008, n = 17), volume of the maternal blood space (r = 0.58, P = 0.048, n = 17), and surface density of syncytiotrophoblast (I = 0 .65, P = 0.023, rr = 17), were positively correlated, and syncytiotrophobla st thickness was negatively; correlated, with maternal plasma IGF-II concen tration (r = - 0.69, P = 0.014, n = 17). Late in gestation, fetal weight, p lacental weight and total exchange surface area in the placenta were each n egatively correlated with maternal plasma IGFBP-2 concentration tall P < 0. 01), while the arithmetic mean thickness of syncytiotrophoblast was positiv ely; correlated with maternal plasma IGFBP-2 concentration. Late in gestati on, the ratio of maternal to fetal plasma glucose was positively correlated with fetal weight (r = 0.54, P = 0.038, n = 15) and the ratio of fetal to maternal plasma urea concentration was positively correlated with placental n eight (r = 0.52, P = 0.046, n = 15). Maternal feed restriction reduced t he ratio of maternal plasma IGF-II to IGFBP-2 in late gestation by 75 per c ent (P = 0.001) and this ratio Ras positiviely correlated with fetal weight (r = 0.56, P = 0.01, n = 20), placental weight (r = 0.59, P = 0.006), plac ental diameter (r = 0.621, P = 0.003), placental volume (r = 0.57, P = 0.00 9), weight of trophoblast (r = 0.51, P = 0.037), weight of fetal capillarie s (r = 0.49, P = 0.046), syncytiotrophoblast surface density (r = 0.611, P = 0.009) and negatively correlated with syncytiotrophoblast thickness (r = -0.55, P = 0.021). Our results suggest that in mid-pregnancy, maternal circ ulating IGF-II promotes placental structural development, while later in pr egnancy., IGFBP-2 inhibits it, and their relative abundance and interaction strongly influences placental structure and function near term. <(c)> 2001 IFPA and Harcourt Publishers Ltd.