The cervical transcriptome changes during the menstrual cycle but does not predict the window of implantation

Abstract

Introduction: The expression of genes in female reproductive organs is influenced by the cyclic changes in hormone levels during the menstrual cycle. While the molecular changes in the endometrium that facilitate embryo implantation have been extensively studied, there is limited knowledge about the impact of the menstrual cycle on cervical cells. Cervical cells can be easily and routinely collected using a cytobrush during gynecological examination, offering a standardized approach for diagnostic testing. In this study we investigated how the transcriptome of cervical cells changes during the menstrual cycle and assessed the utility of these cells to determine endometrial receptivity.

Methods: Endocervical cells were collected with cytobrushes from 16 healthy women at different menstrual cycle phases in natural cycles and from four women undergoing hormonal replacement cycles. RNA sequencing was applied to gain insight into the transcriptome of cervical cells.

Results: Transcriptome analysis identified four differentially expressed genes (DEGs) between early- and mid-secretory samples, suggesting that the transcriptome of cervical cells does not change significantly during the opening of the implantation window. The most differences appeared during the transition to the late secretory phase (2136 DEGs) before the onset of menstruation. Cervical cells collected during hormonal replacement cycles showed 1899 DEGs enriched in immune system processes.

Conclusions: The results of our study suggested that cervical cells undergo moderate transcriptomic changes throughout the menstrual cycle; however, these changes do not reflect the gene expression pattern of endometrial tissue and offer little or no potential for endometrial receptivity diagnostics.

Keywords: cervix uteri; endometrium; menstrual cycle; molecular diagnostic techniques; transcriptome.