Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle.
Uterine microbial disease affects half of all dairy cattle after parturition, causing infertility by disrupting uterine and ovarian function. Infection with Escherichia coli, Arcanobacterium pyogenes, and bovine herpesvirus 4 causes endometrial tissue damage. Toll-like receptors on endometrial cells detect pathogen-associated molecules such as bacterial DNA, lipids, and lipopolysaccharide (LPS), leading to secretion of cytokines, chemokines, and antimicrobial peptides. Chemokines attract neutrophils and macrophages to eliminate the bacteria, although persistence of neutrophils is associated with subclinical endometritis and infertility. Cows with uterine infections are less likely to ovulate because they have slower growth of the postpartum dominant follicle in the ovary, lower peripheral plasma estradiol concentrations, and perturbation of hypothalamic and pituitary function. The follicular fluid of animals with endometritis contains LPS, which is detected by the TLR4/CD14/LY96 (MD2) receptor complex on granulosa cells, leading to lower aromatase expression and reduced estradiol secretion. If cows with uterine disease ovulate, the peripheral plasma concentrations of progesterone are lower than those in normal animals. However, luteal phases are often extended in animals with uterine disease, probably because infection switches the endometrial epithelial secretion of prostaglandins from the F series to the E series by a phospholipase A2-mediated mechanism, which would disrupt luteolysis. The regulation of endometrial immunity depends on steroid hormones, somatotrophins, and local regulatory proteins. Advances in knowledge about infection and immunity in the female genital tract should be exploited to develop new therapeutics for uterine disease.
Institute of Life Science, School of Medicine, Swansea University, Swansea, UK. I.M.Sheldon@swansea.ac.uk
I Martin
IM
Sheldon
James
J
Cronin
Leopold
L
Goetze
Gaetano
G
Donofrio
Hans-Joachim
HJ
Schuberth
D000818:Animals; D002417:Cattle; D005260:Female; D007109:Immunity / Q000276:immunology*; D007239:Infections / Q000276:immunology*; D049590:Postpartum Period / Q000276:immunology*; D014591:Uterine Diseases / Q000276:immunology* / Q000662:veterinary; D014599:Uterus / Q000276:immunology