Author(s): Giulia Tintorri
Mentor(s): Jocelyn Cuthbert
Institution Westminster
Throughout the United States, fertility rates have decreased gradually over the last two decades. This was also associated with a trend of delayed motherhood, characterized by a decrease of fertility rates in younger women and an increase of fertility rates in older women, between 35-44 years of age. The connection between aging and the loss of fertility has been well studied, with the ovary showing early signs of aging compared to other organs. Recently, connections between fibrosis and a decrease in reproductive performance has been made, with fibrosis and overall collagen fiber organization increasing with aging. Pregnancy is known to have major regulatory impacts on the immune system and inflammation, which are major drivers of fibrosis, but the effect of pregnancy on the development and severity of fibrosis in the ovary has not been well investigated. In addition to concerns surrounding decreased fertility, fibrosis represents a potential risk factor in ovarian cancer as well. Fibrosis in various tissues appears to promote a favorable micro-environment environment for tumorigenesis, including the ovaries. Fibrosis driven ovarian cancer risk represents a phenomenon of concern since ovarian cancer, also called as the “silent killer”, is often diagnosed at later stages due to vague symptoms. Elevated fibrotic gene expression in ovarian cancer stroma is correlated with a lower survival rate, suggesting that ovarian fibrosis may be pertinent to ovarian cancer risk and severity. The objective of this study was to examine the impact of pregnancy history and genotype on fibrosis development in aging ovaries. Ovaries were fixed and H&E stained, and assessed for ovarian activity through counting of active or abnormal structures, as well as markers of aging and fibrosis. Ovarian capsule abnormalities were examined, as thickened capsules are associated with fibrosis, in addition to histiocytes, fibrosis, and stromal degeneration. Additional ovary sections were used for quantitative assessment of collagen using picrosirius red staining to examine fibrosis, and immunohistochemistry straining for CD-68 to examine macrophage presence. Only preliminary data has been analyzed, but results suggest that aging was associated with significant changes in the severity of fibrosis, capsule abnormalities, and overall lower ovarian activity, which were expected findings. Pregnancy history was associated with significant differences in the intra-ovarian percentage of histiocytes. Overall, the findings improve our understanding of the development of fibrosis in the ovary, and how pregnancy and genotype drive changes in the aging ovary.