Inhibition of lipopolysaccharide-induced suppression of luteal function in isolated perfused bovine ovaries

Abstract

Recently, we observed that lipopolysaccharide (LPS) suppresses corpus luteum (CL) function in isolated perfused ovaries. It remained unclear if this suppression was due to increased luteal PGF 2α secretion or LPS-induced apoptosis. Therefore, possible impacts of PGF 2α and LPS were inhibited by a non-steroidal anti-inflammatory drug (flunixin) and an endotoxin-binding agent (polymyxin B), respectively. Bovine ovaries with a mid-cycle CL were collected immediately after slaughter and perfused for 240 min. After 50 min of equilibration, either flunixin or polymyxin B (5 μg/ml of each) were added to the perfusion medium of six ovaries, respectively. All ovaries (n = 12) were treated with E. coli LPS (0.5 μg/ml) 60 min after the onset of perfusion, and received 500 I.U. of hCG after 210 min of perfusion. Progesterone and PGF 2α were measured in the effluent perfusate every 10 and 30 min, respectively. Biopsies of the CL were collected every 60 min to determine the mRNA expression of the cytokine TNFA and factors of apoptosis ( CASP3 , -8 ). Flunixin-treatment inhibited the increase of PGF 2α after LPS-challenge that was observed in the polymyxin B-treated (PX-LPS) ovaries. After hCG-stimulation, progesterone secretion increased (P < 0.05) in group PX-LPS but not in the flunixin-treated (F-LPS) ovaries. Compared to initial values before LPS-challenge, luteal mRNA expression of TNFA and CASP3 was increased (P < 0.05) in group F-LPS at 120 and 180 min, respectively, and those of CASP8 was decreased (P < 0.05) in PX-LPS at 60 and 120 min after LPS-treatment. In conclusion, although flunixin managed to inhibit PGF 2α , it did not suffice to successfully prevent LPS-induced apoptosis. However, endotoxin-binding polymyxin B resulted in luteal responsiveness to hCG after LPS-challenge.

Zinc-nanoparticles alleviate the ovarian damage induced by bacterial lipopolysaccharide (LPS) in pregnant rats and their fetuses

“…Similar observations were recorded in the ovarian tissues of bovines treated with LPS (Storni et al. 2022 ). The apoptotic effects induced in the ovaries of offspring maternally treated by LPS may be attributed to the direct apoptotic effects of LPS on the placenta (Ejima et al.…”

Normothermic Machine Perfusion Systems: Where Do We Go From Here?

“…Subsequent studies evaluated ovarian NMP in larger animal models to investigate the freeze-thaw technique of whole ovaries 145 and lipopolysaccharide's effect on the corpus luteum. 146,147 Notably, these models employed shorter perfusion times than naturally required for fully matured follicles and did not achieve complete follicular development. The longest NMP times employed were 20 h in murine, 135,136,138 12 h in rabbit, 139,140,142 and 5 h in human models.…”

“…The administration of therapies through the perfusate has several benefits that make NMP an attractive therapeutic option, including more efficient delivery, lower doses, and reduced unwanted side effects in nontarget organs. 174 The immunomodulatory properties of mesenchymal stem cells 57–159 and multipotent adult progenitor cells 160–162 have shown beneficial effects during liver, lung, and kidney NMP, presumably due to their immunomodulatory properties, which prompt both anti-inflammatory and regenerative responses. 157,160–162 In human models, initially discarded kidneys 160 and livers 161 treated with multipotent adult progenitor cells or preterm-neonate progenitor cells 162 exhibited improved viability, even meeting established criteria.…”