The Gender Gap: The Effect Of Ovarian Function In The Cachectic Response And Il-6 During Cachexia Progression

Cancer cachexia is a devastating condition involving the loss of muscle and fat, as well as biochemical abnormalities due to chronic underlying disease such as cancer. IL-6, a pro-inflammatory cytokine, has proven to be a major driver of cancer cachexia in mouse models and humans. Studies regarding cachexia and IL-6 have largely been conducted in male mice; however, sex differences in cachexia development and IL-6 response using the ApcMin/+ mouse have been detected. The ApcMin/+ mouse has a nonsense mutation in the Apc gene, predisposing it for colon cancer and cachexia. Though proven that hypogonadism is a factor in cachexia in males, research has not been conducted to determine the effect of ovarian function on IL-6 response in the female. The purpose of this study is to determine the effect of ovarian function in the cachectic response and IL-6 during cachexia progression. The hypothesis of this study is that loss of ovarian function will aggravate effects of IL-6 and increase pro-inflammatory macrophages during cachexia cancer progression in the ApcMin/+ mouse. Female ApcMin/+ mice were bred and maintained at USC. Mice were subjected to ovariectomy, systemic overexpression of IL-6, or both procedures. Immunohistochemical analysis within the tibialis anterior muscle was performed to determine fiber cross-sectional area, fiber type analysis, and M1/M2 macrophage populations. Preliminary analysis has validated quantification of cross-sectional area. Future analysis will determine the effects of ovarian function and IL-6 expression on fiber type shifts and macrophage infiltration during the progression of cancer cachexia in female ApcMin/+ mice