Engineering the human endometrium to investigate endometrial-associated disease and infertility — ASN Events
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  3. Engineering the human endometrium to investigate endometrial-associated disease and infertility

Engineering the human endometrium to investigate endometrial-associated disease and infertility (#184)

Harriet Fitzgerald 1 2 3 , Dinasha H Wimalasiri 3 4 5 , Jenna Douglas 3 4 5 , Emily K Jurgec 2 4 , Sarah Broyhill 2 , Emma Salisbury 6 , Joy Chen 4 , Ralf Schittenhelm 7 , Han Lee 7 , Caroline E Gargett 2 3 4 , Beverley Vollenhoven 4
  1. Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
  2. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
  3. Ainsworth Endometriosis Research Institute, University of New South Wales, Sydney, NSW, Australia
  4. Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
  5. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
  6. Department of Chemical and Biological Engineering, Monash University, Clayton, VIC, Australia
  7. Proteomics and Metabolomics Platform, Monash University, Clayton, VIC, Australia

Background: The human endometrium undergoes over 400 cycles of shedding, regeneration, proliferation and differentiation during a woman’s reproductive life. The mechanisms underlying these processes and cellular crosstalk involved in endometrial remodelling remain largely unknown. The upper functionalis layer of the endometrium regenerates from stem/progenitor cells found in the basalis layer, retained during menstrual shedding. Ovarian hormones regulate proliferation of the functionalis and its differentiation into a secretory, receptive tissue, facilitating embryo implantation. Disruption in endometrial function leads to an unreceptive uterus, infertility and diseases e.g. endometriosis and adenomyosis. Our aim was to establish and utilise 3D multicellular models of the human endometrium to investigate the mechanisms regulating endometrial regeneration and remodelling and their role in endometrial disease pathogenesis.

Methods: Human endometrial epithelial organoids (EEO) were established from endometrial epithelial stem/progenitor cells, harvested from control, endometriosis and adenomyosis patients. Epithelial progenitor markers and cellular function was compared between control and disease states to determine the influence of epithelial progenitor function in disease establishment. The basolateral secreted proteome of EEO from control and endometriosis patients was analysed by mass spectrometry. Co-cultures of endometrial epithelia and stroma were established in a collagen-based hydrogel to mimic in vivo endometrium.

Results: EEO were successfully established from endometrial stem/progenitor cells and their differentiated progeny, demonstrating markers of endometrial stem/progenitor cells and changes in their cellular function and identity in vitro. EEO basolateral secretions were altered depending on hormone treatment and disease state, reflecting potential biomarkers for endometriosis diagnosis and infertility. The collagen-based hydrogel supported the growth of EEO and stromal cells in co-culture.

Conclusions: The establishment of human endometrial 3D cell cultures that mimic the regenerative and receptive phases of the endometrium provide essential platforms for the investigation of fundamental endometrial biology, cellular crosstalk, maternal-foetal interactions and the development of new diagnostics and treatments for gynaecological disease.