title: Cervical ripening and parturition in cows are driven by a cascade of pro-inflammatory cytokines.
abstract: The final stages of cervical ripening and parturition resemble an inflammatory process. Although the role of cytokines in both spontaneous and experimentally induced parturitions has been described in several small laboratory animals and humans, the involvement of pro-inflammatory and regulatory cytokines in physiologic parturition in cows has not been determined. In this study, the cytokine expression profiles were assessed in bovine cervical tissue at several stages of pregnancy and at parturition. Serial biopsy samples of the cervix were obtained from 10 cows on day 185 and day 275 of pregnancy (which was on average 5.4 days before parturition) and at parturition. Messenger RNA expression levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)alpha were determined using real-time polymerase chain reaction and the number of neutrophils and eosinophils was estimated by Luna and Sirius Red staining. At parturition, IL-8 expression had increased 430-fold (p < 0.001) when compared with that of the day 185 of pregnancy, large numbers of neutrophils had invaded the cervix while eosinophils remained scarce, IL-1beta had increased eightfold (p < 0.05) and IL-6 had not changed significantly. Additionally, IL-10 was increased by 10-fold (p < 0.001) and TNFalpha decreased by 57% (p < 0.05) when compared with that of the day 185 of pregnancy. The large increase in expression of IL-8, enabling the influx of neutrophils, is indicative of its important role in the final stage of cervical ripening and at parturition. As previous studies have shown that neutrophils excrete matrix metalloproteinases (MMP), this might contribute to softening of the cervix. In contrast, the only slightly increased levels of IL-1, steady concentrations of IL-6 and decreased TNFalpha, the potential consequences of increased IL-10 expression, indicate that final cervical of cows in ripening at term parturition is an inflammatory process influenced by regulatory cytokines.
authors.affiliation: Department of Pathobiology, Division of Anatomy and Physiology, Utrecht University, Utrecht, The Netherlands. e.vanengelen@uu.nl
authors.forename: E
authors.initials: E
authors.lastname: van Engelen
authors.forename: M W
authors.initials: MW
authors.lastname: de Groot
authors.forename: V N A
authors.initials: VN
authors.lastname: Breeveld-Dwarkasing
authors.forename: M E
authors.initials: ME
authors.lastname: Everts
authors.forename: G C
authors.initials: GC
authors.lastname: van der Weyden
authors.forename: M A M
authors.initials: MA
authors.lastname: Taverne
authors.forename: V P M G
authors.initials: VP
authors.lastname: Rutten
mesh_terms: D000818:Animals; D002417:Cattle; D020070:Cervical Ripening / Q000502:physiology*; D002584:Cervix Uteri / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D005865:Gestational Age; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D007958:Leukocyte Count; D009504:Neutrophils / Q000502:physiology; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10