Repeated intrauterine infusions of lipopolysaccharide alter gene expression and lifespan of the bovine corpus luteum

Abstract

Inflammation of the uterus is associated with disturbed ovarian function and reduced reproductive performance in dairy cows. To investigate the influence of endometritis on the bovine corpus luteum, 8 heifers received intrauterine infusions with either phosphate-buffered saline (PBS; 9mL) or Escherichia coli lipopolysaccharide (LPS; 3µg/kg of body weight diluted in 9mL of PBS) at 6-h intervals from 12h before and until 9d after ovulation during 2 cycles in a random order (ovulation=d 1). An untreated cycle was examined before and after PBS and LPS cycles, and the mean values from both untreated cycles were used as control. In all cycles, blood sampling and ultrasonography of the ovaries were performed on d 0, 1, 2, 4, 6, 8, 9, 10, 12, 15, 18, and then every 2d until ovulation. Endometrial cells were collected for cytology and quantitative real-time reverse transcriptase PCR on d 0, 6, and 9, and on d 0 and 6, respectively, and luteal tissue was collected for quantitative real-time reverse transcriptase PCR on d 6 and 9. Both, PBS and LPS infusions induced subclinical endometritis, which was accompanied by increased endometrial mRNA abundance of proinflammatory cytokines IL1β, IL8, and tumor necrosis factor α. Additionally, LPS challenge induced premature luteolysis, which was characterized by increased plasma concentrations of PGF2α metabolite, decreased plasma progesterone concentrations, and reduced luteal size and blood flow compared with the control. The luteal mRNA expression of the LPS receptor TLR4, PGE synthase, and the apoptosis-related factor CASP3 were higher, and those of steroidogenic factors STAR and HSD3B, the PGF receptor, and the angiogenic factor VEGFA121 were lower after LPS challenge compared with the control. In conclusion, repeated intrauterine LPS infusions during the first 9d of the estrous cycle alter gene expression and shorten the lifespan of the bovine corpus luteum.

Intramammary infusion of lipopolysaccharide promotes inflammation and alters endometrial gene expression in lactating Holstein cows

“…Other papers, including some by this group (Cerri et al, 2012;Davoodi et al, 2016), have also included genes that had lower differential magnitude. Compared with recent studies that used intrauterine LPS infusion (Lüttgenau et al, 2016) or cows diagnosed with subclinical and clinical endometritis (Salilew-Wondim et al, 2016), the present study observed significantly smaller fold change in the endometrium gene expression. Even in the papers describing uterine disease, genes with lower fold change are also presented.…”

“…Tumor necrosis factor-α induces premature release of PGF 2α from the endometrium (Miyamoto et al, 2000), resulting in luteolysis and a gradual decrease of progesterone levels that are incompatible with gestation (Giri et al, 1990;Skarzynski et al, 2000;Hansen et al, 2004). Recently, Lüttgenau et al (2016) reported that repeated intrauterine infusions of LPS at the onset of the estrous cycle promoted premature luteolysis and altered endometrial and corpus luteum (CL) gene expression. Therefore, the negative effect of infection on reproductive tract functionality is probably due to a direct effect of endotoxin added to indirect effects of inflammatory mediators.…”

Impacts of chronic and increasing lipopolysaccharide exposure on production and reproductive parameters in lactating Holstein dairy cows

“…The reproductive and inflammatory response to acute LPS exposure has been well chronicled (Giri et al, 1990;Lüttgenau et al, 2016). However, natural infection likely causes a more persistent and dynamic LPS exposure, reflective of bacterial overgrowth and proliferation.…”

Uterine inflammation affects the reproductive performance of dairy cows: A review

“…Herath et al (2009) also showed in vivo and in vitro evidence for production of PGE compared with PGF 2α in cows with E. coli infection. Lüttgenau et al (2016), however, found the opposite effect in heifers. Intrauterine infusion of LPS decreased progesterone concentrations and reduced the lifespan of the corpus luteum in the cycle when LPS was infused, but also in the subsequent cycle.…”