Abstract
Regular menstrual shedding and repair of the endometrial functionalis is unique to humans and higher-order primates. The current consensus postulates endometrial glands to have a single-tubular architecture, where multi-potential stem cells reside in the blind-ending glandular-bases. Utilising fixed samples from patients, we have studied the three-dimensional (3D) micro-architecture of the human endometrium. We demonstrate that some non-branching, single, vertical functionalis glands originate from a complex horizontally interconnecting network of basalis glands. The existence of a multipotent endometrial epithelial stem cell capable of regenerating the entire complement of glandular lineages was demonstrated by in vivo lineage tracing, using naturally occurring somatic mitochondrial DNA mutations as clonal markers. Vertical tracking of mutated clones showed that at least one stem-cell population resides in the basalis glands. These novel findings provide insight into the efficient and scar-less regenerative potential of the human endometrium. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Highlights
The endometrium is a highly regenerative tissue that undergoes more than 400 monthly cycles of proliferation and sloughing under the influence of ovarian hormones during a woman’s lifetime
Tanaka et al explored the clonality of epithelial cells by analysing DNA extracted from individual endometrial glands using the X-linked androgen receptor gene as an indirect marker of non-random X chromosome inactivation, and reported on the clonal constitution of glandular cells and luminal epithelium (LE) [5]; Kim et al proposed that cell divisions and ancestry may be surreptitiously recorded by identifying replication errors that naturally accumulate in a clock-like manner during aging based on the hypothesis that all daughter cells originate from a common ancestor [3,5]
Menstrual shedding and subsequent repair of the endometrial functionalis layer is a process unique to humans and higher-order primates. This distinctive regeneration pattern makes traditional in vivo lineage tracing studies in rodent models, that confirm the existence of an adult epithelial stem cell, less relevant to the human endometrium [8,9,10,11,12]
Summary
The endometrium is a highly regenerative tissue that undergoes more than 400 monthly cycles of proliferation and sloughing under the influence of ovarian hormones during a woman’s lifetime. Tanaka et al explored the clonality of epithelial cells by analysing DNA extracted from individual endometrial glands using the X-linked androgen receptor gene as an indirect marker of non-random X chromosome inactivation, and reported on the clonal constitution of glandular cells and luminal epithelium (LE) [5]; Kim et al proposed that cell divisions and ancestry may be surreptitiously recorded by identifying replication errors that naturally accumulate in a clock-like manner during aging based on the hypothesis that all daughter cells originate from a common ancestor [3,5] These studies implicitly assume the endometrial glandular organisation to be blind-ending single tubes, a hypothesis yet to be confirmed. This method allows lineages to be traced and, in several instances previously, the stem cell niche to be identified [13,14,15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
