Objectives: Hormones released from the placenta are thought to adapt maternal metabolism so that nutrients are optimally partitioned to the fetus for growth. Likely central to this process are imprinted genes, such as Igf2 (insulin-like growth factor 2) that is highly expressed by the conceptus and vital for promoting fetal growth. Here, we explore how deletion of Igf2 in the placental endocrine zone impacts on maternal metabolism and fetal nutrient supply and growth.
Methods: TpbpaCre females were mated with male Igf2-floxed mice to produce whole litters with selective Igf2 under-expression in the placental endocrine cells (Jz-Igf2UE). On day 16 of gestation, dams underwent either a glucose/insulin tolerance test, or were anesthetised and received a non-metabolisable analogue of glucose (3H-methyl-D glucose) to determine maternal-fetal glucose transfer. Maternal pancreas was harvested for beta cell mass quantification and maternal blood and placentas were collected for the proteomic identification of placental hormones.
Results: Compared to pregnant control dams, Jz-Igf2UE dams showed greater glucose tolerance and insulin sensitivity. Moreover, Jz-Igf2UE dams showed reduced pancreatic beta cell mass, but greater glucose-stimulated insulin secretion (measured during the glucose tolerance test). Materno-fetal glucose transfer and fetal growth were decreased in Jz-Igf2UE dams. Proteomic analysis of maternal plasma identified reduced prolactin levels in Igf2UE dams, while placental analysis identified 310 proteins altered between control and Jz-Igf2UE dams, such as pentraxin, leptin receptor and TNRF1.
Conclusions: Igf2 influences placental hormone production, with important implications for maternal metabolic changes that promote fetal nutrient supply and growth.