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

Abstract

In postpartum dairy cows, subclinical endometritis (SCE) is characterized by persistent endometrial inflammation, which has profound detrimental effects on subsequent reproductive performance. To date, transcriptomic studies related to this condition were either based on biopsy-derived whole-endometrium tissue or endometrial swab or cytobrush samples, thus masking effects of disease on cell type-specific gene expression. This study tested the hypothesis that different endometrial health statuses are associated with distinct transcription profiles of endometrial stromal, glandular, and luminal epithelial cells. At 44 d postpartum (DPP), endometrial biopsies were taken from dairy cows (n = 24) classified as healthy, recovered from SCE, or affected by persistent SCE, according to endometrial cytology taken at 21 and 44 DPP. Stromal, glandular, and luminal epithelial cells were isolated from the whole-tissue biopsy by laser capture microdissection, and the cell-specific transcription profiles were determined by RNA sequencing. Differential gene expression was analyzed with DESeq2 (https: / / bioconductor .org/ packages/ release/ bioc/ html/ DESeq2 .html).Results demonstrated that global transcriptomic profiles and corresponding lists of differentially expressed genes between cows with different health statuses were distinct among cell types. Results also showed that although healthy and recovered cows presented similar endometrial clinically healthy phenotypes at 44 DPP, the prior presence of immune cells still affected the transcriptome of endometrial cells at this stage, delaying complete functional recovery. Recovery or persistence of inflammation was associated with gene expression patterns involved not only in immune function but also in tissue remodeling, cell adhesion, and uterine receptivity in a cell type-specific manner. Identifying these signatures may contribute to the development of novel diagnostic tools and therapeutic strategies. In addition, these results may help to define preventive measures or ways to stimulate recovery from endometrial inflammation, thus helping to restore the fertility of postpartum dairy cows.

Transcriptomics analysis of the bovine endometrium during the perioestrus period

“…More recent work investigating individual cell types showed that three different cell types isolated from bovine endometrium by laser microdissection at Day 15 of the oestrous cycle demonstrated different molecular signatures for luminal and glandular epithelium, as well as for stromal cells, which showed the greatest differences in gene expression [ 69 ]. Differences in these cell types were equally pronounced in post-partum bovine endometrium, and progesterone gave rise to different patterns of expression in the three cell types [ 70 ].…”

Investigating Polymorphisms and Expression Profile of Immune, Antioxidant, and Erythritol-Related Genes for Limiting Postparturient Endometritis in Holstein Cattle

“…There have been recent studies targeting novel genes specific to livestock endometritis susceptibility using genome-wide association analysis [ 32 , 41 ], but up to this point, no studies have examined the link between the SNPs in these genes and endometritis risk. The European cow ( Bos taurus ) gene sequences used in our study, which were reported in PubMed, are the first to demonstrate this association.…”

“…Leucocyte recruitment during inflammation has been reported to be interceded by inflammatory cytokines and complement fragments [ 78 ]. Endometritis is also characterized by unchecked extended inflammation linked to tissue damage, which causes the release of molecular forms accompanying injury, further aggravating inflammation and guaranteeing its perseverance [ 32 ]. Afterwards, oxidative stress is brought on by the extreme gathering of ROS [ 79 ].…”

“…Quantitative trait loci (QTLs) are then mapped [ 30 ]. Only modest progress has been made in determining the molecular genetic roots of endometritis in animals [ 31 , 32 ]. This study used PCR-DNA sequencing and real-time PCR to examine potential immune ( TLR4 , TLR7 , TNF-α , IL10 , NCF4 , and LITAF ), antioxidant ( ATOX1 , GST , and OXSR1 ), and erythritol-related ( TKT , RPIA , and AMPD1 ) gene efficacy as candidates for prediction and tracking endometritis resistance/susceptibility in postparturient Holstein dairy cows.…”

Whole genome re-sequencing reveals artificial and natural selection for milk traits in East Friesian sheep

“…The TRAF3 gene is essential for immune function of mammary epithelial cells in cows ( 50 ). The FGF16 gene was identified as differentially expressed in endometrial glandular, luminal, and stromal cells of cows with persistent inflammation and recovery from postpartum endometritis, demonstrating that the FGF16 gene is a potential candidate gene to promote the transition from an inflammatory to a healthy state in postpartum dairy cows ( 51 ). As well, in a genome-wide association analysis of dairy cows, SIN3A was identified as a candidate gene for individual laboratory cheese yield and protein percentage traits in milk traits ( 52 ).…”