Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse

OBJECTIVES: The aim of this study was to determine the effect of pregnancy and delivery mode on cytokine expression in the pelvic organs and serum of lysyl oxidase like-1 knockout (LOXL1 KO) mice, which develop pelvic organ prolapse after delivery. METHODS: Bladder, urethra, vagina, rectum, and blood were harvested from female LOXL1 KO mice during pregnancy, after vaginal or cesarean delivery, and from sham cesarean and unmanipulated controls. Pelvic organs and blood were also harvested from pregnant and vaginally delivered wild-type (WT) mice and from unmanipulated female virgin WT controls. Specimens were assessed using quantitative real-time reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay. RESULTS: Both CXCL12 and CCL7 mRNA were significantly up-regulated in the vagina, urethra, bladder, and rectum of pregnant LOXL1 KO mice compared with pregnant WT mice, suggesting systemic dysregulation of both of these cytokines in LOXL1 KO mice as a response to pregnancy.The differences in cytokine expression between LOXL1 KO and WT mice in pregnancy persisted after vaginal delivery. CCL7 gene expression increases faster and to a greater extent in LOXL1 KO mice, translating to longer lasting increases in CCL7 in serum of LOXL1 KO mice after vaginal delivery, compared with pregnant mice. CONCLUSIONS: Lysyl oxidase like-1 KO mice have an increased cytokine response to pregnancy perhaps because they are less able to reform and re-cross-link stretched elastin to accommodate pups, and this resultant tissue stretches during pregnancy. The up-regulation of CCL7 after delivery could provide an indicator of level of childbirth injury, to which the urethra and vagina seem to be particularly vulnerable.