(008) Chronic High Fat Diet Decreases Vaginal Smooth Muscle Tone but does not Affect Pelvic Floor Skeletal Muscle in Mice

Abstract

Abstract Introduction Pelvic organ prolapse (POP) is a disease that affects the physical and mental health of women, as well as their quality of life. POP, regardless of severity, can be a direct cause of female sexual dysfunction (FSD) by producing pain during intercourse or a general 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. Studies have shown that obesity and a high fat diet (HFD) can weaken skeletal muscle by increasing collagen deposition and inducing muscle apoptosis. Objectives There is paucity in the literature of animal studies that have specifically investigated the effect of obesity on the support structures of the pelvic floor and how it contributes to POP. The objective of this study is to examine the structure and function of the vagina and pelvic floor in female mice fed a chronic 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 (IC) 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. IC 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 vaginal smooth muscle. Interestingly, the function and composition of pelvic skeletal muscle was unaffected by HFD. As the vagina serves as a primary support structure to the pelvic organs, lack in muscle contractility and increase in relaxation following HFD suggests that obesity-induced POP may play a direct role in FSD. Disclosure