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Retained fetal membranesRetained fetal membranes (RFM) are defined as the failure of an animal to expel the fetal membranes, within 24 hours of the end of parturition. Retained placenta is an alternative name used for RFM. There is some variation in the literature about the duration of retention that defines the clinical disorder. Some prefer to define retention as being for12 hours, but the timing is arbitrary and most normal cows expel the fetal membranes within a few hours of parturition. The incidence of RFM varies amongst herds, but is typically 5 to 10% of animals.The importance of RFM is that they are associated with reduced milk yield and an increased risk of metritis. MetritisMetritis is most common within 10 days of parturition. Metritis is characterized by an enlarged uterus and a watery red-brown fluid, to viscous off-white purulent, uterine discharge, which often has a fetid odour (Sheldon et al 2006). The incidence of metritis varies between breed, country and herd, but in a study of the records from 97,318 cows in the USA, the lactation incidence of metritis, including RFM, was 21% (Zwald et al 2004). However, in some studies the incidence is as high as 40% of the herd. The associated clinical signs are used to classify the severity of disease, which varies from unapparent disease to fatal toxaemic metritis. Clinical endometritisClinical endometritis is defined as the presence of a purulent uterine discharge detectable in the vagina of cattle 21 days or more postpartum, or a mucopurulent discharge detectable in the vagina after 26 days postpartum (Sheldon et al 2006). The incidence of clinical endometritis is around 10 to 20%, with variation between breed, country and herd; a typical study reported that 16.9% of 1,865 dairy cows were affected in Canada (LeBlanc et al

Many species of bacteria produce toxins such as cholesterol-dependent cytolysins that form pores in cell membranes. Membrane pores facilitate infection by releasing nutrients, delivering virulence factors, and causing lytic cell damage - cytolysis. Oxysterols are oxidized forms of cholesterol that regulate cellular cholesterol and alter immune responses to bacteria. Whether oxysterols also influence the protection of cells against pore-forming toxins is unresolved. Here we tested the hypothesis that oxysterols stimulate the intrinsic protection of epithelial cells against damage caused by cholesterol-dependent cytolysins. We treated epithelial cells with oxysterols and then challenged them with the cholesterol-dependent cytolysin, pyolysin. Treating HeLa cells with 27-hydroxycholesterol, 25-hydroxycholesterol, 7α-hydroxycholesterol, or 7β-hydroxycholesterol reduced pyolysin-induced leakage of lactate dehydrogenase and reduced pyolysin-induced cytolysis. Specifically, treatment with 10 ng/ml 27-hydroxycholesterol for 24 h reduced pyolysin-induced lactate dehydrogenase leakage by 88%, and reduced cytolysis from 74% to 1%. Treating HeLa cells with 27-hydroxycholesterol also reduced pyolysin-induced leakage of potassium ions, prevented mitogen-activated protein kinase cell stress responses, and limited alterations in the cytoskeleton. Furthermore, 27-hydroxycholesterol reduced pyolysin-induced damage in lung and liver epithelial cells, and protected against the cytolysins streptolysin O and Staphylococcus aureus α-hemolysin. Although oxysterols regulate cellular cholesterol by activating liver X receptors, cytoprotection did not depend on liver X receptors or changes in total cellular cholesterol. However, oxysterol cytoprotection was partially dependent on acyl-CoA:cholesterol acyltransferase (ACAT) reducing accessible cholesterol in cell membranes. Collectively, these findings imply that oxysterols stimulate the intrinsic protection of epithelial cells against pore-forming toxins and may help protect tissues against pathogenic bacteria.

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: After parturition, dairy cows have between two and five months to conceive again if they are to maintain sustainable productivity. The reproductive biology events that need to be completed to meet this objective are the restoration of the uterus to a receptive state that would support conception and the return of ovarian cyclic activity with ovulation of competent oocytes. Unfortunately, most modern dairy cows have uterine bacterial infections, which are associated with clinical disease in about 40% of animals and subclinical endometritis in other cases. The risk of disease is increased by events such as retained fetal membranes and dystocia. However, the endometrium mounts a robust defence against infection mediated by the innate immune system. There are effective treatments for clinical disease, but even after resolution of the disease the animals are sub‐fertile. Understanding the mechanisms of uterine disease may lead to improved therapeutics and help veterinary surgeons to consider strategies for the prevention of this disease that is endemic in modern dairy cattle.