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Sudden changes in endometrial cell gene expression allow embryo implantation to occur

21 September 2020
Appeared in BioNews 1064

The window during which embryo implantation occurs in humans is marked by changes in gene expression in the cells of the womb lining, a new study has shown.

During the human menstrual cycle, the endometrium goes through a process of shedding and regeneration. Researchers led by Stanford University's Dr Stephen Quake investigated gene expression during this process, providing new genetic information at the single-cell level.

'By studying both the static and dynamic aspects of the tissue, we discovered molecular characterisations of hallmark events such as the window of implantation (WOI),' Dr Quake and his colleagues wrote in their paper published in Nature Medicine. The WOI is a short period of time when the endometrium is ready for embryo implantation.

In the study, the researchers obtained endometrial samples from 19 healthy donors between four and 27 days after the onset of their last menstrual cycle. They performed single-cell RNA sequencing to analyse the genes and markers that are expressed by the endometrial cells throughout the menstrual cycle.

They discovered six different cell types, two of which the researchers named ciliated epithelium and unciliated epithelium. Cilia are tiny hair-like structures on the surface of the cell. The presence of ciliated epithelial cells in the endometrium has been speculated since the 1890s but little has been reported on this cell type. The researchers, however, found this cell type to be present throughout the course of the menstrual cycle.

Importantly, they reported a change in gene expression, particularly among unciliated epithelial cells, that corresponded with the opening of the WOI.

Four major phases of endometrial transformation were discovered. At the beginning of the fourth phase unciliated epithelial cells began to express genes whose expression are linked to the WOI. Furthermore, at the same time, stromal fibroblasts (another cell type discovered in the endometrial samples) also increased the expression of certain genes and markers associated with the process of decidualisation, which significant changes to cells of the endometrium ready for pregnancy.

In contrast to the abrupt opening of the WOI, the researchers discovered that it closed gradually towards the end of phase four into phase one of the next cycle. If embryo implantation does occur, the researchers noted that the embryo triggers the development of stromal fibroblasts.

This research gives an insight into the healthy endometrium, but the data may also be used to help further understand the molecular mechanisms involved in the development of endometrial disease, such as adenomyosis, endometriosis and cancer.
Endometrium undergoes gene expression shifts during menstrual cycle, single-cell study finds
GenomeWeb |  14 September 2020
Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle
Nature Medicine |  14 September 2020
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