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Lipopolysaccharide alters CEBPβ signaling and reduces estradiol production in bovine granulosa cells
CABI Agriculture and Bioscience, Volume: 3, Issue: 1, Pages: 1 - 15
Swansea University Author: Martin Sheldon
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DOI (Published version): 10.1186/s43170-022-00133-3
BackgroundBacterial infection of the uterus in postpartum dairy cows limits ovarian follicle growth, reduces blood estradiol concentrations, and leads to accumulation of bacterial lipopolysaccharide (LPS) in ovarian follicular fluid. Although treating granulosa cells with LPS in vitro decreases the...
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BackgroundBacterial infection of the uterus in postpartum dairy cows limits ovarian follicle growth, reduces blood estradiol concentrations, and leads to accumulation of bacterial lipopolysaccharide (LPS) in ovarian follicular fluid. Although treating granulosa cells with LPS in vitro decreases the expression of the estradiol synthesis enzyme CYP19A1 and reduces estradiol secretion, the molecular mechanisms are unclear. The transcription factor CCAAT enhancer binding protein beta (CEBPβ) not only facilitates the transcription of LPS regulated cytokines, but also binds to the promoter region of CYP19A1 in humans, mice, and buffalo. We hypothesized that LPS alters CEBPβ signaling to reduce CYP19A1 expression, resulting in decreased estradiol secretion.MethodsBovine granulosa cells were isolated from small/medium or large follicles and treated with LPS in the presence of FSH and androstenedione for up to 24 h.ResultsTreatment with LPS increased CXCL8 and IL6 gene expression and reduced estradiol secretion in granulosa cells from both small/medium and large follicles. However, LPS only reduced CYP19A1 expression in granulosa cells from large follicles. Treatment with LPS increased CEBPB expression and reduced CEBPβ nuclear localization in granulosa cells from small/medium follicles, but not granulosa cells from large follicles.ConclusionsAlthough LPS reduces estradiol synthesis in bovine granulosa cells, the effects of LPS on CYP19A1 and CEBPβ are dependent on follicle size.
Granulosa cell; Estradiol; Lipopolysaccharide; Inflammation
Faculty of Medicine, Health and Life Sciences
This study was supported by Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD084316 and by Agriculture and Food Research Initiative Competitive Grant No. 2020-67015-31015 from the USDA National Institute of Food and Agriculture.