Long-term maintenance of human endometrial epithelial organoids and their stem cell properties

Abstract

The endometrium undergoes dynamic changes throughout the menstrual cycle and pregnancy, which is unique to primates. Endometrium remodeling is essential for the implantation and nutritional support of the conceptus. Despite this, the role of uterine glands in driving endometrial tissue remodeling is still poorly understood. To address this, a 3-dimensional culture system was used to generate endometrial epithelial organoids from human endometrium biopsies. These organoids are genetically stable, long-term expandability. They reproduce some functions of uterine glands in vivo. The epithelial organoids exhibit characteristics of stem cells, with the proportion of stem cells increasing with culture time and passage number. Long-term maintenance of organoids strongly expressed stemness related genes accompanied by a decrease expression in mature epithelial gene, which suggests the organoids had switched from a mature stage to a progenitor stage. Thus we proposed the possible makers for epithelial progenitors. Meanwhile, long-term cultured organoids exhibit an increase in the proportion of luminal epithelial stem cells, accompanied by a decrease of glandular epithelial stem cells. Organoids also show hormone responsiveness, reflecting the various stages of the menstrual cycle and early pregnancy.