Decreased endopelvic fascia elastin content in uterine prolapse.
BACKGROUND
Genital prolapse is a debilitating manifestation of pelvic floor dysfunction. The cause of this condition has not been elucidated. The purpose of this study was to determine elastin content and RNA expression of related enzymes of elastin synthesis in uterosacral ligament biopsies from women with severe prolapse, and controls with normal pelvic support.


METHODS
Biopsies were taken from the uterosacral ligament tissue of 31 women with Grade III or greater prolapse and 29 women with normal pelvic support. Elastin content was assessed by measuring desmosine using radioimmunoassay, and quantitative real time PCR was performed to quantify mRNA levels of lysyl oxidase (LOX), lysyl oxidase like-1 (LOXL1), LOXL2 and fibulin-5 (FIB-5).


RESULTS
The mean desmosine concentration found in uterosacral ligaments of women with prolapse (n =26) was 103.3+/-59.3 pmolD/mgP compared to controls (n =29) 120.5+/-47.4 pmolD/mgP (p =0.1943). In the subgroup of subjects with complete procidentia (n =8), mean desmosine concentration was 50.6+/-25.8 and 127.1+/-42.2 pmolD/mgP in age-matched controls (n =12) (p <0.05). In tissue from subjects with more than 2 vaginal deliveries (n =18), the mean desmosine concentration was 99.9+/-60.7 and 133.0+/-44.0 pmolD/mgP in controls (n =17) (p <0.05). Expression of LOX, LOXL1 and LOXL2 decreased 8.2-fold+/-3.4, 5.0-fold+/-1.7 and 15.2-fold+/-5.2, respectively (mean+/-SD) in cases versus controls (p<0.05). Expression of FIB-5 was increased 3.1-fold+/-0.7 compared to controls (p<0.05).


CONCLUSIONS
Significantly decreased desmosine content was measured in the uterosacral ligament tissue from women with prolapse versus controls in women with parity >2 and in women with complete procidentia. Suppression of mRNA for LOX and two LOX isoenzymes was correspondingly present. These results suggest that altered elastin metabolism is present in women with uterine prolapse.
D000328:Adult; D000368:Aged; D001706:Biopsy; D003895:Desmosine / Q000378:metabolism; D004549:Elastin / Q000096:biosynthesis / Q000172:deficiency* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005205:Fascia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes; D008022:Ligaments / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010384:Pelvic Bones / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014596:Uterine Prolapse / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D007527:Isoenzymes; D012333:RNA, Messenger; D003895:Desmosine; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase