How fibroblast/hormone interactions affect endometrial function

The endometrium is a dynamic tissue that undergoes dynamic cyclic proliferation and differentiation to prepare for pregnancy. Endometrial stromal fibroblasts (eSFs) are key regulators of pregnancy success.

How the cells interact with circulating levels of ovarian-derived estradiol (E₂) and progesterone (P₄) is unknown. Results of a new genome-wide analysis suggest that the complex interplay between eSFs, E₂ and P₄ has a significant impact on endometrial function or dysfunction¹.

To further understand the dynamic interactions, a team of researchers studied the effects of E₂, P₄, and their combination (E₂+P₄) on the DNA methylome and transcriptome and their interplay in normal eSF.

The effects on the cells were analyzed at 14 days of exposure to the hormones, mimicking the timeframe of a typical menstrual cycle.

The cells used in the study were derived from women with and without endometriosis. Those without the disease and who had no known gynecologic or systemic disorders served as the study’s control group.

Researchers only included endometrial samples from extensively screened volunteers without any gynecologic disorders and no uterine pathology (NUP), with confirmed in vitro eSF progesterone responsiveness.

The researchers investigated 485,577 methylation targets across the genome and found that E₂ and P₄ alone and in combination affected the DNA methylome to varying extents and with distinct patterns in eSF.

Related: Impact of endometrial thickness and abnormal uterine bleeding on endometrial cancer

The study also showed that hormone-DNA methylome dynamics differ under normal and disease conditions, and that the stage of endometriosis affects the hormone-methylome response. The most blunted response to the hormones was seen in cells from women with advanced endometriosis.

Novel responses to E2 that had not reported before were seen in eSFs from women with the disease. The different aberrant DNA methylation signatures in eSFs from the group with endometriosis suggest that there are distinct subtypes of the disease.

__

Reference

1. Houshdaran S, Oke AB, Fung JC, et al. Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis. PLoS Genet. 2020;16(6):e1008601. Published 2020 Jun 17. doi:10.1371/journal.pgen.1008601

__

Image credit: By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18158244