No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

Biomechanical studies were performed on biopsies of the rectus sheath, round and uterosacral ligaments as well as anterior and posterior vaginal walls of women with or without genital prolapse. In the second study, 96 healthy women in their fifth decade, were compared with 94 similar women with genital prolapse surgery Their clinical connective tissue markers were assessed by standardised methods and their first childbirth data were collected from hospital notes. The progress of the first labour was analysed by multiple logistic regression in the 2 groups of women. In the third study, 665 primiparous women who had their first baby during the previous 7 to 12 months, had their clinical connective tissue markers assessed as in the second study. Data from their first labour were then collected from the hospital notes and compared to the connective tissue markers by standard multiple regression analysis. Results: In-vitro biomechanical data showed that the round ligament properties were different in women with and without genital prolapse. They were also different amongst women under and over 40 years of age without genital prolapse. In women without genital prolapse, the elasticity of the rectus sheath and the round ligament differed from each other. In women with genital prolapse, the anterior vaginal wall and the uterosacral ligament were different from each other. In the second study, women with uterocervical prolapse had a shorter active first stage of labour than women without prolapse. When women with any type of genital prolapse were compared to women without prolapse, there was no difference in the duration of labour. The study is likely not to have had adequate power to detect a difference in the second stage of labour. More women in the prolapse group had knee hyperextension but there was no difference in the mobility of the upper limb joints. In the third study, primiparous women with increased joint mobility had a shorter second stage of labour. Connective tissue properties play an important role in pelvic floor function.

Human labour is shown to be an inflammatory process, which involves a marked leukocyte infiltrate into myometrium during labour. My study focused on the role of chemokines, key mediators of leukocyte trafficking, in labour. Previous gene array data obtained from human labouring myometrium showed that the mRNA expression of the following chemokines was increased in term labouring myometrium, CCL2, CCL20, CXCL1, CXCL5, CXCL8. I decided to focus on myometrial expression of these chemokines and also to include CCL5, another important chemokine. My data confirmed that the expression of human myometrial chemokines was increased in labour and that their expression was up regulated by cytokines and mechanical stretch via NFKB and MAPK, but decreased by prostaglandins and oxytocin via PLC. I also studied the expression of myometrial chemokine receptors, which may mediate some of the effects of chemokines on myometrial function and/or act as decoys, minimising the effects of locally produced chemokines. I found that the expression of the chemokine receptors decreased with the onset of labour, mainly through the action of prostaglandins and oxytocin. I then used the established model of LPS-­‐induced preterm labour (PTL) in the mouse and found that chemokines and cytokines both increased in the myometrium and placenta. CCL2 is consistently increased with human labour and has been shown to be important in rodent parturition too. I therefore studied the impact of LPS in the CCR2 (the main receptor for CCL2) knockout mouse. There was less inflammation in both the myometrium and placenta and a better pup survival rate in the CCR2-/- mouse. However, the PTL was not delayed, suggesting that CCR2 is not essential for the induction of PTL labour by LPS in the mouse. I then turned my attention to CCL20, which acts only via CCR6. It is known to drive dendritic cell recruitment and I found that its expression was increased with labour, while that of its receptor was reduced. Functionally, I found that CCL20 up-regulated the myometrial expression of chemokines. Next I used the LPS-induced preterm labour model in the mouse and found that CCR6 knockout delayed LPS-induced preterm delivery and improved pup survival. These findings were associated with much lower inflammation in myometrium and plasma. These data suggest that CCR6 could be a therapeutic target in the management of PTL. Chemokines play an important role both in the induction of term labour and in infection induced PTL. Chemokine inhibitors may delay the onset of PTL and improve the fetal outcome.

No description available.