Placental-Specific Igf2 Deficiency Alters Developmental Adaptations to Undernutrition in Mice

TLDR

Fetal growth patterns strongly influence later infant health outcomes. The study investigates how placental‑specific Igf2P0 regulates placental adaptation to maternal undernutrition. Researchers compared morphology and nutrient transfer in wild‑type versus Igf2P0‑deficient placentas under normal and 80 % feeding conditions. Loss of Igf2P0 blocks the normal increase in amino‑acid transport, reduces the labyrinthine zone, impairs Slc38a2 expression, and alters maternal insulin, corticosterone, and glucose, underscoring its essential role in placental adaptation to undernutrition.

Abstract

The pattern of fetal growth is a major determinant of the subsequent health of the infant. We recently showed in undernourished (UN) mice that fetal growth is maintained until late pregnancy, despite reduced placental weight, through adaptive up-regulation of placental nutrient transfer. Here, we determine the role of the placental-specific transcript of IGF-II (Igf2P0), a major regulator of placental transport capacity in mice, in adapting placental phenotype to UN. We compared the morphological and functional responses of the wild-type (WT) and Igf2P0-deficient placenta in WT mice fed ad libitium or 80% of the ad libitium intake. We observed that deletion of Igf2P0 prevented up-regulation of amino acid transfer normally seen in UN WT placenta. This was associated with a reduction in the proportion of the placenta dedicated to nutrient transport, the labyrinthine zone, and its constituent volume of trophoblast in Igf2P0-deficient placentas exposed to UN on d 16 of pregnancy. Additionally, Igf2P0-deficient placentas failed to up-regulate their expression of the amino acid transporter gene, Slc38a2, and down-regulate phosphoinositide 3-kinase-protein kinase B signaling in response to nutrient restriction on d 19. Furthermore, deleting Igf2P0 altered maternal concentrations of hormones (insulin and corticosterone) and metabolites (glucose) in both nutritional states. Therefore, Igf2P0 plays important roles in adapting placental nutrient transfer capacity during UN, via actions directly on the placenta and/or indirectly through the mother.