Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA235

Poster Communications

The role of Igf2 in regulating maternal-fetal resource allocation in mouse pregnancy

J. Lopez-Tello1, A. Sferruzzi-Perri1

1. University of Cambridge, Centre for Trophoblast Research, Cambridge, United Kingdom.

  • Figure. The effect of selectively manipulating Igf2 expression in the placental endocrine zone on maternal body composition, circulating metabolites, conceptus weight and placental structure. Numbers of dams used for body composition and metabolites were >4 per genotype. Number of fetuses and placentas for conceptus weights were >30 per genotype. Number of placentas that were assessed structurally were 8-9 per genotype. Data presented as mean ± SEM and analyzed by T test (*** P< 0.0001, ** P<0.01, * P<0.05,

During pregnancy, adequate nutrients must be supplied to the fetus for growth with sufficient resources also partitioned to the mother to maintain her health. Failure to appropriately allocate resources can lead to pregnancy complications and abnormal fetal development with long-term consequences for maternal and offspring health. The placenta is central to this "tug-of-war" over resources as it is responsible for materno-fetal nutrient transport and secretes hormones with suspected effects on maternal physiology. However compared to placental transport function, less is known about the regulation of placental endocrine function and its significance for fetal nutrient allocation and growth. Insulin-like growth factor-2 (Igf2) is a growth-promoting paternally-expressed imprinted gene abundantly expressed in feto-placental tissues. Previous work shows that altering conceptus Igf2 modifies both the maternal metabolic profile, and placental nutrient transfer in a manner consistent with the maternal ability to support the fetal genetic drive for growth1-5. However the precise role of Igf2 in placental endocrine function and materno-fetal resource allocation is unknown. Aim: To determine the effect of selectively manipulating Igf2 expression in the mouse placental endocrine zone, on maternal metabolism, nutrient allocation and fetal growth. Methods: Transgenic mice were crossed to produce entire litters with complete deletion or over-expression of Igf2 in the placental endocrine zone using the TpbpaCre line (leaving the placental transport zone, fetus and mother un-manipulated, Igf2/Tpbpa and H19DMR/Tpbpa respectively). On day 16 of pregnancy (term ~20 days), dams were anaesthetised with fentanyl-fluanisone:midazolam in sterile water (i.p. at ratio of 1:1:2) and blood was collected before schedule 1 killing. Maternal organs and conceptuses were weighed and placental structure analysed. Procedures were performed abiding to the UK Home Office Animals (Scientific Procedures) Act 1986. Results: Deletion of Igf2 in the placental endocrine zone reduced maternal kidneys and liver weights and circulating lipid concentrations (Figure). However, over-expression of Igf2 in the placental endocrine zone increased maternal heart weight and circulating glucose, but reduced non-esterified fatty acid (NEFA) and triglyceride concentrations. In both models, placental weights were heavier and related to an increase in the endocrine zone or the transport zone when Igf2 was over-expressed or Igf2 deleted, respectively. In addition, deletion of placental endocrine zone Igf2 marginally reduced fetal weight. Conclusion: Igf2 expression in placental endocrine zone is important in determining maternal metabolic profile in pregnancy, which affects resource allocation and potentially fetal growth. Work is underway to further assess changes on day 19 of pregnancy.

Where applicable, experiments conform with Society ethical requirements