Molecular characterization of age-associated ovarian multinucleated giant cells

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B634
Abstract ID: 6466

Presenting Author:
Aubrey Converse , Research Assistant Professor at Northwestern Univ. Feinberg Sch. of Med.

Abstract:

Ovarian function begins to decline in the mid-30s in humans, earlier than any other tissue. Although the precise mechanisms driving ovarian aging have not been fully elucidated, chronic inflammation may be an influential factor. We previously found reproductively old mammalian ovaries contain macrophage-derived multinucleated giant cells (MNGCs), while reproductively young ovaries are void of these cells. MNGCs are associated with chronic inflammation in other tissues, but the reason for their presence and their function in the aging ovary remain unknown. To begin to fill this knowledge gap, we performed the first molecular characterization of ovarian MNGCs. Immunohistochemical and RNAscope analyses indicate ovarian MNGCs express iNOS and Ly6C, markers of classically activated and monocyte-derived macrophages. MNGCs also express macrophage and osteoclast markers such as Gpnmb, Acp5, and Galectin-3, and high levels of Tgfb1. TGFβ1 is increased in the proteome of reproductively old mouse ovaries compared to young and is a known stimulator of fibroblast collagen secretion. We previously found reproductively old ovaries have increased collagen accumulation and stiffness compared to young ovaries. Thus, MNGCs may indirectly contribute to these age-related phenotypes by producing TGFβ1. We are continuing our characterization of these cells through RNAseq analysis to determine their origins, phenotype, and potential functions to predict the consequences of MNGCs in the ovary.