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The human endometrium at a single-cell level

Researchers have characterised the transcriptomic transformation of the human endometrium during the menstrual cycle at single-cell resolution. 

Human endometrium

During the menstrual cycle, the human endometrium undergoes monthly remodelling, shredding and regeneration. This has only been in observed in a few species, including apes and Old World monkeys. It is not seen in other commonly used model organisms such as the mouse and zebrafish. The cycle is divided into two major phases – the proliferative and the secretory. As it has relevance for human fertility and regenerative biology, characterisation of endometrial transformation during the menstrual cycle is important.

The endometrium is unique. Unlike other tissues, it consists of multiple cell types that vary dramatically in state during the monthly cycle. During the cycle, these cell types remodel and undergo various forms of differentiation at relatively rapid rates. Histology has been able to establish morphological definitions of menstrual phases. In addition, whole-tissue transcriptomic profiling has advanced these definitions to a molecular and quantitative level. As a result, experts have translated these findings into clinics to determine timing of the window of implantation (WOI) during in vitro fertilisation and embryo transfer.

Single-cell analysis

In a study, published in Nature Medicine, researchers sought to decouple and define endometrial cell types and states. They utilised high resolution single-cell RNA-sequencing (RNA-seq) to study both the static and dynamic aspects of the tissue. They collected endometrial biopsies from 19 healthy ovum donors, 4-27 days after onset of their menstrual bleed.

From profiling seven endometrial cell types, including a previously uncharacterised ciliated cell type, the team discovered characteristic signatures for each cell type and phase. They noted that ciliated cells were consistently present within healthy endometrium, but dynamically changed in abundance across the menstrual cycle. Their data also suggested that the WOI begins with an abrupt and strong transcriptomic activation in unciliated epithelia, along with a more continuous transition in stromal fibroblasts. The team suggest that, due to this abruptness, it should be possible to diagnose the opening of the WOI with higher precision for in vitro fertilisation and embryo transfer.

The team believe that researchers could use this dataset as a healthy human baseline for endometrial diseases and for evaluation of model systems. They hope that the dating system will be useful for studies in clinical fertility and endometrial biology and to also study the impact menstrual cycle variation can have on molecular and behavioural measurements in females.

Image credit: Cartoon vector created by brgfx –