Department of Animal Biosciences, Swedish University of Agricultural Sciences, P.O. Box 7023, SE-75007 Uppsala, Sweden.
Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7023, SE-75007 Uppsala, Sweden.
Int J Mol Sci. 2024 Sep 11;25(18):9832. doi: 10.3390/ijms25189832.
Endometritis is an inflammatory disease that negatively influences fertility and is common in milk-producing cows. An in vitro model for bovine endometrial inflammation was used to identify enrichment of -acting regulatory elements in differentially methylated regions (DMRs) in the genome of in vitro-cultured primary bovine endometrial epithelial cells (bEECs) before and after treatment with lipopolysaccharide (LPS) from , a key player in the development of endometritis. The enriched regulatory elements contain binding sites for transcription factors with established roles in inflammation and hypoxia including NFKB and Hif-1α. We further showed co-localization of certain enriched -acting regulatory motifs including ARNT, Hif-1α, and NRF1. Our results show an intriguing interplay between increased mRNA levels in LPS-treated bEECs of the mRNAs encoding the key transcription factors such as AHR, EGR2, and STAT1, whose binding sites were enriched in the DMRs. Our results demonstrate an extraordinary -regulatory complexity in these DMRs having binding sites for both inflammatory and hypoxia-dependent transcription factors. Obtained data using this in vitro model for bacterial-induced endometrial inflammation have provided valuable information regarding key transcription factors relevant for clinical endometritis in both cattle and humans.
子宫内膜炎是一种炎症性疾病，会对生育能力产生负面影响，在产奶牛中较为常见。本研究建立了体外奶牛子宫内膜炎模型，通过检测脂多糖（LPS）处理前后体外培养的原代奶牛子宫内膜上皮细胞（bEECs）基因组中差异甲基化区域（DMR）中 - 作用调控元件的富集情况，来识别与子宫内膜炎发生发展相关的关键因子。结果表明，这些富含调控元件的区域包含了一些已证实与炎症和低氧反应相关的转录因子（如 NFKB 和 Hif-1α）的结合位点。我们还发现某些富集的 - 作用调控基序（如 ARNT、Hif-1α 和 NRF1）存在共定位现象。此外，我们发现 LPS 处理的 bEECs 中转录因子（如 AHR、EGR2 和 STAT1）的 mRNA 水平增加，这些转录因子的结合位点在 DMR 中富集。这些结果表明，这些 DMR 中存在着炎症和低氧依赖的转录因子的结合位点，表现出令人着迷的相互作用。本研究通过体外细菌诱导子宫内膜炎模型获得的数据，为牛和人类临床子宫内膜炎的关键转录因子提供了有价值的信息。
