Herath Shan, Lilly Sonia T, Santos Natalia R, Gilbert Robert O, Goetze Leopold, Bryant Clare E, White John O, Cronin James, Sheldon I Martin
Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, UK.
Reprod Biol Endocrinol. 2009 May 29;7:55. doi: 10.1186/1477-7827-7-55.
Contamination of the uterine lumen with bacteria is ubiquitous in cattle after parturition. Some animals develop endometritis and have reduced fertility but others have no uterine disease and readily conceive. The present study tested the hypothesis that postpartum cattle that develop persistent endometritis and infertility are unable to limit the inflammatory response to uterine bacterial infection.
Endometrial biopsies were collected several times during the postpartum period from animals that were subsequently infertile with persistent endometritis (n = 4) or had no clinical disease and conceived to first insemination (n = 4). Quantitative PCR was used to determine the expression of candidate genes in the endometrial biopsies, including the Toll-like receptor (TLR 1 to 10) family of innate immune receptors, inflammatory mediators and their cognate receptors. Selected proteins were examined by immunohistochemistry.
The expression of genes encoding pro-inflammatory mediators such as interleukins (IL1A, IL1B and IL6), and nitric oxide synthase 2 (NOS2) were higher during the first week post partum than subsequently. During the first week post partum, there was higher gene expression in infertile than fertile animals of TLR4, the receptor for bacterial lipopolysaccharide, and the pro-inflammatory cytokines IL1A and IL1B, and their receptor IL1R2. The expression of genes encoding other Toll-like receptors, transforming growth factor beta receptor 1 (TGFBR1) or prostaglandin E2 receptors (PTGER2 and PTGER4) did not differ significantly between the animal groups. Gene expression did not differ significantly between infertile and fertile animals after the first week postpartum. However, there were higher ratios of IL1A or IL1B mRNA to the anti-inflammatory cytokine IL10, during the first week post partum in the infertile than fertile animals, and the protein products of these genes were mainly localised to the epithelium of the endometrium.
Cattle may maintain fertility by limiting the inflammatory response to postpartum bacterial infection in the endometrium during the first week after parturition.
产后母牛子宫腔细菌污染普遍存在。一些动物会发生子宫内膜炎且生育力降低,但其他动物没有子宫疾病且能顺利受孕。本研究检验了以下假设:发生持续性子宫内膜炎和不育的产后母牛无法限制对子宫细菌感染的炎症反应。
在产后期间多次采集子宫内膜活检样本,这些动物随后要么因持续性子宫内膜炎而不育(n = 4),要么没有临床疾病且首次输精即受孕(n = 4)。采用定量PCR来测定子宫内膜活检样本中候选基因的表达,包括天然免疫受体的Toll样受体(TLR 1至10)家族、炎症介质及其同源受体。通过免疫组织化学检测选定的蛋白质。
编码促炎介质如白细胞介素(IL1A、IL1B和IL6)以及一氧化氮合酶2(NOS2)的基因在产后第一周的表达高于随后时期。在产后第一周,不育动物中细菌脂多糖受体TLR4、促炎细胞因子IL1A和IL1B及其受体IL1R2的基因表达高于可育动物。编码其他Toll样受体、转化生长因子β受体1(TGFBR1)或前列腺素E2受体(PTGER2和PTGER4)的基因在两组动物之间无显著差异。产后第一周后,不育和可育动物之间的基因表达无显著差异。然而,在产后第一周,不育动物中IL1A或IL1B mRNA与抗炎细胞因子IL10的比值高于可育动物,且这些基因的蛋白质产物主要定位于子宫内膜上皮。
母牛可能通过在产后第一周限制对子宫内膜产后细菌感染的炎症反应来维持生育力。