Expression of neuropeptide Y and its receptors in the cardinal ligaments and uterosacral ligaments in patients with pelvic organ prolapse

Abstract

To evaluate the distribution of neuropeptide Y and its receptors in the cardinal ligament and uterosacral ligaments in women with and without pelvic organ prolapse (POP). Sixteen patients with pelvic organ prolapse entered the study. All patients were evaluated by pelvic organ prolapse quantitation (POP-Q). Group A consisted of six patients with grade I , II POP, and group B comprised ten patients with grade III, IV POP. Eight nonfunctional ovarian tumor patients without POP were recruited as control subjects. Biopsies of cardinal ligament and uterosacral ligament were obtained from each woman during surgery. Immunohistochemical study with polyclonal antibody against a general nerve marker S-100 and neuropeptide Y was performed on paraffin-embedded sections of all the samples. In addition, mRNA levels of the human NPY-Y1 and NPY-Y2 receptors were assessed in both patients and controls. (1) NPY immunoreactivities were identified in both cardinal ligament and uterosacral ligament NPY immunoreactive nerve fibers were insignificantly lower in POP patients (P > 0.05). The distribution pattern of NPY was similar in cardinal ligament and uterosacral ligament (P > 0.05). (2) mRNAs encoding the NPY-Y1 and NPY-Y2 receptors were detected in the pelvic supporting tissues. Besides the expected NPY-Y1 PCR products, an additional 97 bp long amplicon originating from an alternative splicing event was found in most tissues studied. (3) In cardinal ligaments, mRNA encoding NPY-Y1 receptor had a significant difference between group A (3.9 +/- 1.0) and B (6.0 +/- 1.5), and between control (3.4 +/- 0.9) and group B (P = 0.019, P = 0.004), while there was no significant difference between group A and controls (P = 0.082). In uterosacral ligaments, mRNA encoding NPY-Y1 receptor had no significant difference between Group A (6.0 +/- 1.1) and B (6.3 +/- 0.7), or between group A and controls (4.8 +/- 0.7; P = 0.151, P = 0.690); while there was a significant difference between group B and controls (P = 0.016). (4) mRNA encoding NPY-Y2 receptor had no significant difference between controls (0.49 +/- 0.34, 0.61 +/- 0.15), group A (0.56 +/- 0.21, 0.67 +/- 0.13) and group B (0.85 +/- 0.43, 0.69 +/- 0.21) patients in cardinal ligament and uterosacral ligaments (P > 0.05). (5) mRNA encoding NPY-Y1 (P = 0.084) and NPY-Y2 (P = 0.470) receptors had no significant difference between cardinal ligament and uterosacral ligament. There are NPY and NPY receptors in cardinal and uterosacral ligaments. The increased expression of NPY Y1 receptor may be related to local blood flow reduction and structural changes of pelvic supporting tissue.