The Content Of MtDNA And MtDNA⁴⁹⁷⁷ In Peripheral Blood And Pelvic Floor Tissues Of Patients With Pelvic Organ Prolapse.

Objective: Pelvic organ prolapse (POP) is a global health problem, affecting adult women of all ages. It decreases considerably their quality of life. However, little is known about the pathogenesis of POP. Now, people believe the pathophysiology of POP is related to aging in the pelvic organ support tissues, and mitochondrial dysfunction is one of the major contributors to aging. The accumulation of mitochondrial DNA (mtDNA) somatic mutations and oxidative damage has been shown to be important contributors to tissue aging. Somebody also suggest the single mtDNA mutations may induce cell apoptosis so that the tissue become aging early. Moreover, mtDNA mutations can influence the synthesis and metabolism of mitochondrial correlative enzymes in electron transport chain and lead to mitochondrial dysfunction, followed by tissue weakness. Therefore, this study examined the content of total mtDNA and 4977 deletion of mtDNA (mtDNA⁴⁹⁷⁷) in peripheral blood and different pelvic floor tissues of patients with and without POP. It was to investigate the correlation between alternations of mtDNA and progression of POP, and new ideas in the prevention and treatment of POP.Methods: We took samples from patients in the department of gynecology and obstetrics of the second hospital of Hebei Medical University, between January 2009 and October 2010. 26 patients with POP (stagesⅠ–Ⅲ) were recruited as the study group; 21 benign gynecological diseases patients with non-POP (stage 0) were the control group. All the patients had undergone hysterectomies. Women with heart disease, diabetes, nerve degenerative disease, malignancies or who had undergone prior pelvic radiation and those subjects receiving estrogen/progesterone therapy were excluded from the study. There were no significant differences between two groups of their age, parity, body mass index (BMI), percentage of menopause and cesarean posterior wall tissues, there were insignificant difference between POP group(1.187±1.306, 0.955±0.701, 0.883±0.949) and non-POP group (1.466±1.111, 0.953±0.688, 0.798±0.478)(P>0.05). In peripheral blood, uterosacral ligament, vaginal anterior and posterior wall tissues, the content of mtDNA⁴⁹⁷⁷ had a significant increase between POP group(3.488±4.100, 6.181±8.408, 6.903±7.293, 8.300±8.594) and non-POP group(1.077±0.895, 0.875±0.877, 1.149±1.173, 1.031±0.720)(P<0.05). Either POP or non-POP group, there were no significant difference of the content of mtDNA and mtDNA⁴⁹⁷⁷ between vaginal anterior and posterior wall tissues(P>0.05).Accompanied with the advanced stage of POP (analysis between POP-0 and POP-â…¢stage), we found a evident trend towards a decrease in the content of mtDNA in uterosacral ligament(P<0.05), while in peripheral blood, vaginal anterior and posterior wall tissues, the trend was insignificant(P>0.05). Just the opposite, in peripheral blood, uterosacral ligament, vaginal anterior and posterior wall tissues, a significantly increased proportion of mtDNA⁴⁹⁷⁷, accompanied by advanced-stage POP, was found (P<0.05).3 Correlation analysisThere were no correlation between the content of mtDNA and mtDNA⁴⁹⁷⁷ in peripheral blood, uterosacral ligament and vaginal wall tissue(r= 0.236,-0.371,0.062, P>0.05). The content of mtDNA in peripheral blood of POP patients had a positive correlation with that in uterosacral ligament(r=0.627, P<0.05), while there was no correlation of the content of mtDNA⁴⁹⁷⁷ between peripheral blood and uterosacral ligament of POP patients(r=-0.067, P>0.05). Conclusions:1 In uterosacral ligament tissue of POP patients, the content of mtDNA was obviously lower than that of non-POP patients and this tendency seemed to be more prominent in advanced-stage POP. Thus, the pathogenesis of POP may be related to a decline in mtDNA content of uterosacral ligament tissue.2 In peripheral blood, uterosacral ligament and vaginal wall tissue of POP patients, the content of mtDNA⁴⁹⁷⁷ was evidently higher than that in non-POP patients. And accompanied with the advanced stage of POP, this tendency posterior wall tissues, there were insignificant difference between POP group(1.187±1.306, 0.955±0.701, 0.883±0.949) and non-POP group (1.466±1.111, 0.953±0.688, 0.798±0.478)(P>0.05). In peripheral blood, uterosacral ligament, vaginal anterior and posterior wall tissues, the content of mtDNA⁴⁹⁷⁷ had a significant increase between POP group(3.488±4.100, 6.181±8.408, 6.903±7.293, 8.300±8.594) and non-POP group(1.077±0.895, 0.875±0.877, 1.149±1.173, 1.031±0.720)(P<0.05). Either POP or non-POP group, there were no significant difference of the content of mtDNA and mtDNA⁴⁹⁷⁷ between vaginal anterior and posterior wall tissues(P>0.05).Accompanied with the advanced stage of POP (analysis between POP-0 and POP-â…¢stage), we found a evident trend towards a decrease in the content of mtDNA in uterosacral ligament(P<0.05), while in peripheral blood, vaginal anterior and posterior wall tissues, the trend was insignificant(P>0.05). Just the opposite, in peripheral blood, uterosacral ligament, vaginal anterior and posterior wall tissues, a significantly increased proportion of mtDNA⁴⁹⁷⁷, accompanied by advanced-stage POP, was found (P<0.05).3 Correlation analysisThere were no correlation between the content of mtDNA and mtDNA⁴⁹⁷⁷ in peripheral blood, uterosacral ligament and vaginal wall tissue(r= 0.236,-0.371,0.062, P>0.05). The content of mtDNA in peripheral blood of POP patients had a positive correlation with that in uterosacral ligament(r=0.627, P<0.05), while there was no correlation of the content of mtDNA⁴⁹⁷⁷ between peripheral blood and uterosacral ligament of POP patients(r=-0.067, P>0.05).Conclusions:1 In uterosacral ligament tissue of POP patients, the content of mtDNA was obviously lower than that of non-POP patients and this tendency seemed to be more prominent in advanced-stage POP. Thus, the pathogenesis of POP may be related to a decline in mtDNA content of uterosacral ligament tissue.2 In peripheral blood, uterosacral ligament and vaginal wall tissue of POP patients, the content of mtDNA⁴⁹⁷⁷ was evidently higher than that in non-POP patients. And accompanied with the advanced stage of POP, this tendency seemed to be more evident. Thus, in peripheral blood and pelvic tissues, the accumulation of mtDNA⁴⁹⁷⁷ may be the molecular event involved in the occourence and progression of POP.3 A depletion of mtDNA and an increase of mtDNA⁴⁹⁷⁷ were both in uterosacral ligament tissue of POP patients, it conform that uterosacral ligament damage is closely related with POP and it as the main support power of pelvic tissue should not be ignored.