Introduction: Pelvic organ prolapse (POP) affects 41% women and is a direct cause of female sexual dysfunction (FSD) by producing pain during intercourse or a reluctance to engage in sexual activity. The largest risk factors for POP include parity, obesity, and advanced age. Obesity, a modifiable risk factor, is believed to increase intra-abdominal pressure and weaken the pelvic floor muscles and fascia. The impact of obesity on vaginal smooth muscle versus pelvic floor skeletal muscle has not been studied in animal models of POP. We will examine the structure and function of the vagina and pelvic floor in female mice fed a chronic high fat diet (HFD).
Methods: Adult female C57/Blk6N mice (10 weeks, n=32) were fed a control (10% kcal fat) or HFD (45% kcal fat) for 24 weeks. Ex vivo external vaginal sphincter contraction to increasing concentrations of adrenergic agonist norepinephrine and relaxation to nitric oxide donor DEA NONOate and electric field stimulation (EFS) was measured. Iliococcygeus muscles of the pelvic floor were isolated and set to optimal length and tetanic contractions were performed at increasing frequencies to asses absolute and specific force. Fatigue was measured following repetitive stimulations over 5 minutes. Iliococcygeus muscle fiber types were characterized with anti-myosin antibodies and cross-sectional area (CSA) of each fiber type was measured.
Results: Vaginal sphincter adrenergic-mediated contraction was a significantly decreased in HFD-fed mice (Fig 1A; p<0.05). The vaginal sphincter smooth muscle relaxation in response to a nitric oxide donor was greater in the HFD mice (Fig 1B; p<0.05). Neurogenic-mediated EFS vaginal relaxations were also enhanced in the HFD mice (p<0.05). Surprisingly, chronic HFD did not impact iliococcygeus muscle specific force, absolute force, or muscle fatigue (Fig 1C). Furthermore, HFD did not affect the CSA or population of type I, IIa, IIX, or IIb iliococcygeus muscle fibers.
Conclusions: HFD-induced obesity in mice leads to pelvic floor weakness by enhancing relaxation and decreasing tone of the external vaginal sphincter. Interestingly, the function or composition of pelvic skeletal muscle was unaffected. As the vagina provides significant support to pelvic organs, obesity-induced decreased vaginal sphincter tone and structure may lead to POP and FSD. Source of
Funding: International Society for the Study of Women’s Sexual Health, Alpha Omega Alpha Medical Society