Oral Presentation 6th Australian Health and Medical Research Congress 2012

IMPAIRED LABYRINTH MORPHOGENESIS AND INTERHEMAL MEMBRANE FORMATION IN LY6E MUTANT MICE (#194)

David G Simmons 1 , Michael B Langford 1 , David R Natale 2
  1. University Of Queensland, ST LUCIA, QLD, Australia
  2. Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Alberta, Canada

The efficient transfer of nutrients, wastes and gases across the placenta occurs by a variety of mechanisms, such as simple diffusion, facilitated diffusion and active transport. The aberrant formation of placental architecture can impact on all these routes of transfer by reducing the surface area available for exchange, or by altering the cellular organisation or thickness of the barrier separating the fetal and maternal blood spaces (the interhemal membrane).
We have characterised a placental phenotype in Ly6e deficient mice in which placental architecture is affected. Ly6e encodes a small molecular weight, GPI-linked glycoprotein of the Ly-6 family of cell surface proteins. We previously found that Ly6e is expressed within synT-I cells of the mouse placenta in a pattern reminiscent of Syna. Like Syna, genetic deletion of Ly6e is embryonic lethal by mid-gestation, a phenotype originally attributed to heart abnormalities1. Our analysis demonstrates that Ly6e-/- placentae are abnormal, both in the organisation of the villous tree and in the ultrastructural organisation of the interhaemal membrane. On a gross level, the labyrinth appears underdeveloped compared to heterozygous or wildtype controls, displaying a reduction in villous branching. Further indicating a morphogenesis defect, electron microscopy of Ly6e-/- interhaemal membranes revealed areas of disrupted syncytiotrophoblast fusion and an overall increase in barrier thickness, all consistent with profound deficiencies in placental function. Furthermore, these placental phenotypes precede the appearance of heart abnormalities, and are therefore the likely cause of lethality in these mice. 

  1. Zammit DJ, Berzins SP, Gill JW, Randle-Barrett ES, Barnett L, Koentgen F, Lambert GW, Harvey RP, Boyd RL, Classon BJ. Essential role for the lymphostromal plasma membrane Ly-6 superfamily molecule thymic shared antigen 1 in development of the embryonic adrenal gland. Mol Cell Biol. 2002 Feb;22(3):946-52.