Progesterone differentially affects the transcriptomic profiles of cow endometrial cell types

Abstract

Background The endometrium is a heterogeneous tissue composed of luminal epithelial (LE), glandular epithelial (GE), and stromal cells (ST), experiencing progesterone regulated dynamic changes during the estrous cycle. In the cow, this regulation at the transcriptomic level was only evaluated in the whole tissue. This study describes specific gene expression in the three types of cells isolated from endometrial biopsies following laser capture microdissection and the transcriptome changes induced by progesterone in GE and ST cells. Results Endometrial LE, GE, and ST cells show specific transcriptomic profiles. Most of the differentially expressed genes (DEGs) in response to progesterone are cell type-specific (96%). Genes involved in cell cycle and nuclear division are under-expressed in the presence of progesterone in GE, highlighting the anti-proliferative action of progesterone in epithelial cells. Elevated progesterone concentrations are also associated with the under-expression of estrogen receptor 1 (ESR1) in GE and oxytocin receptor (OXTR) in GE and ST cells. In ST cells, transcription factors such as SOX17 and FOXA2, known to regulate uterine epithelial-stromal cross-talk conveying to endometrial receptivity, are over-expressed under progesterone influence. Conclusions The results from this study show that progesterone regulates endometrial function in a cell type-specific way, which is independent of the expression of its main receptor PGR. These novel insights into uterine physiology present the cell compartment as the physiological unit rather than the whole tissue.

Effect of Chinese patent medicine Kunling Pill on endometrial receptivity: A clinical trial, network pharmacology, and animal-based study

“…The maximal ERα and PR expression occurred in the menstrual cycle's mid-to-late proliferative phase (25). It was noted that elevated progesterone correlated with the under-expression of ERα in glandular epithelium (26). In our study, we detected a similar pattern where ERα decreased in COH mice, along with a high level of progesterone concentration.…”

Subclinical endometritis differentially affects the transcriptomic profiles of endometrial glandular, luminal, and stromal cells of postpartum dairy cows

“…The present study aimed to describe the transcriptomic profiles associated with different endometrial cell types in cows with differing health statuses. To confirm results from former studies showing that endometrial cell types present very different transcriptomic signatures (Chankeaw et al, 2021a;Pereira et al, 2022), LCM was successfully used here to isolate cell types and study their specific response to persistent inflammation of the endometrium or recovery. The relevance of the approach was demonstrated by the different transcriptomic profiles between groups of cows with contrasting health status, showing that the majority (>90%) of DEG between healthy, recovered, and persistent cows was cell type-specific.…”

“…Endometrial tissue processing and staining procedures were performed as previously described (Chankeaw et al, 2021a,b;Pereira et al, 2022). Briefly, 8-µm-thick sections were cut from the tissue blocks on a cryostat (Cryotome FSE, Thermo Scientific) set at −20°C, mounted on glass slides at 4°C, and immersed for 60 s in 75% ethanol inside the cryostat chamber (−20°C).…”

“…All steps of the gene-level exploratory analysis and differential transcription analysis were carried out as described previously (Pereira et al, 2022), using the RNAseq workflow described by Love et al (2015;updated version: https: / / bioconductor .org/ help/ course -materials/ 2017/ CSAMA/ labs/ 2 -tuesday/ lab -03 -rnaseq/ rnaseqGene _CSAMA2017 .html). The Salmon method (Patro et al, 2017) was used to quantify transcript abundance, and the Tximport method (Soneson et al, 2015; R package version 1.8.0, https: / / www .r -project .org/ ) was then used to import Salmon's transcript-level quantifications.…”

“…The bovine endometrium is a complex and heterogeneous tissue, and quantification of gene transcription from the whole endometrium may not reflect cell-specific transcription. In postpartum dairy cows, stromal (ST), glandular epithelial (GE), and luminal epithelial (LE) endometrial cells isolated by laser capture microdissection (LCM) exhibit very distinct molecular signatures (Chankeaw et al, 2021a), differentially influenced by progesterone (Pereira et al, 2022) and negative energy balance (Chankeaw et al, 2021b).…”