Oral Presentation Australasia Extracellular Vesicles Conference 2017

The role of extracellular vesicles in embryo-maternal cross-talk essential for regulating pregnancy. (#21)

Lois A Salamonsen 1 , Hong P Nguyen 2 , Richard Simpson 3 , David Greening 3
  1. The Hudson Institute of Medical Research, Melbourne, VIC, Australia
  2. Brain Cancer Group, Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
  3. Department of Biochemistry and Genetics, School of Molecular Sciences, La Trobe University, Melbourne, Victoria, Australia

To establish pregnancy, the embryo (blastocyst), enters the uterine cavity, where it must attach to the endometrial surface epithelium, then invade further, to develop the placenta during the first trimester.  The endometrium is only ‘receptive’ to implantation briefly during the mid-secretory progesterone-dominated phase of the cycle. Uterine fluid provides the microenvironment for implantation and contains soluble glandular secretions that enhance blastocyst development. 

We proposed that EVs/exosomes of endometrial origin, contribute to this microenvironment in women, and that transfer of their cargo to the trophoblast cells on the  blastocyst surface, may improve implantation potential.

We identified exosomes within human uterine fluid, and derived from human endometrial luminal epithelial cells, ECC11.  Importantly, these exosomes contained unique cohorts of both miRNA1and proteins2. Quantitative proteomic analyses demonstrated that hormonal stimuli of ECC1 cells as occurs across a normal menstrual cycle, extensively altered programming of exosome content. While 663 common exosome proteins were identified, a further 254 proteins were packaged specifically under estrogen stimulation and 126 proteins only when progesterone was present; 35% (189) of these proteins are endometrial epithelial exosome specific.

Importantly, these endometrial exosomes were internalised by cultured human trophoblast cells and enhanced their adhesive capacity.  Importantly, this increased adhesion was significantly higher when the parent endometrial cells were treated with estrogen plus progesterone, mimicking the receptive endometrium, and is in accord with the adhesion molecule content within exosomes.  Both fibronectin and focal adhesion kinase (FAK) pathway members (total FAK and pFAK proteins) were increased in trophoblast cells, indicating that the FAK pathway is likely involved in increased adhesive capacity of the trophoblast cells following exosome uptake.

Further targeted studies may enable novel nano-diagnostics and nano-therapeutics to improve infertility, pregnancy loss and preeclampsia and possibly new methods for contraception. 

1Ng et al. Plos One 2013, 8(3) e58502; 2Greening et al. Biol.Reprod. 2016, 92:38