Expression of lysyl oxidase and transforming growth factor beta2 in women with severe pelvic organ prolapse.
OBJECTIVE
To determine the mRNA expression of lysyl oxidase (LOX) and transforming growth factor beta2 (TGF beta2) in subjects with advanced pelvic organ prolapse as compared to asymptomatic controls.


METHODS
Seventeen women undergoing vaginal hysterectomy were recruited for the study. Nine women with grade > or = 3 pelvic organ prolapse by the Baden-Walker grading scale were recruited. Eight subjects without pelvic organ prolapse or urinary incontinence undergoing hysterectomy for other indications were recruited as asymptomatic controls. A 1-cm portion of the bilateral distal uterosacral ligaments was excised and immediately frozen at -80 degrees C. Total RNA was extracted, quantified and subjected to reverse transcription for cDNA synthesis. beta-Actin was used as the reference for the semiquantitative analysis. Known volumes of the polymerase chain reaction (PCR) products for each reaction were electrophoresed in agarose gels stained with ethidium bromide and photographed with a digital camera. The optical density for each sample was measured by using computerized image analysis software. The relative abundance of each specific message was calculated as the ratio of PCR product for LOX or TGF beta2 divided by the amount of PCR product for beta-actin from the same sample.


RESULTS
The mean age of the study subjects was 55.7 years (38-67) versus 47.1 for the controls (44-54). Mean parity was 4.4 for the study subjects and 2.7 for the controls. Seventy-eight percent of the study subjects were postmenopausal, and 14% of the controls postmenopausal. All postmenopausal subjects had at least 1 month of estrogen therapy prior to surgery. The mean LOX/beta-actin ratio for the study group was 0.35 as compared to 0.72 for the control group. This was statistically significant with a p value of 0.049. The mean TGF beta2/beta-actin ratio for the study group was 0.12 as compared to 0.20 for the control group. This was not statistically significant (p = 0.46).


CONCLUSIONS
Patients with severe pelvic organ prolapse (grade > or = 3) have a significant reduction in the mRNA expression of lysyl oxidase as compared to asymptomatic controls. The mRNA expression of TGF beta2 was not statistically different between the 2 groups. These findings lend further credence to the concept of specific biochemical changes in the pelvic floor in women with pelvic organ prolapse.
Kobak
William
W
Illinois Urogynecology, Oak Lawn, USA. william.kobak@advocatehealth.com
Lu
Jing
J
Hardart
Anne
A
Zhang
Chunying
C
Stanczyk
Frank Z
FZ
Felix
Juan Carlos
JC
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007045:Hysterectomy, Vaginal; D008593:Menopause; D008875:Middle Aged; D010298:Parity; D017773:Pelvic Floor; D011247:Pregnancy; D011446:Prospective Studies; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014596:Uterine Prolapse / Q000235:genetics*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D008249:Protein-Lysine 6-Oxidase