Histological analyses data for: Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures

The ovary is one of the first organs to exhibit signs of aging,
characterized by reduced tissue function, chronic inflammation, and
fibrosis. Multinucleated giant cells (MNGCs), formed by macrophage fusion,
typically occur in chronic immune pathologies, including infectious and
non-infectious granulomas and the foreign body response, but are also
observed in the aging ovary. The function and consequence of ovarian MNGCs
remain unknown as their biological activity is highly context-dependent,
and their large size has limited their isolation and analysis through
technologies such as single-cell RNA sequencing. In this study, we define
ovarian MNGCs through a deep analysis of their presence across age and
species using advanced imaging technologies as well as their unique
transcriptome using laser capture microdissection. MNGCs form complex
interconnected networks that increase with age in both mouse and nonhuman
primate ovaries. MNGCs are characterized by high Gpnmb expression, a
putative marker of ovarian and non-ovarian MNGCs. Pathway analysis
highlighted functions in apoptotic cell clearance, lipid metabolism,
proteolysis, immune processes, and increased oxidative phosphorylation and
antioxidant activity. Thus, MNGCs have signatures related to degradative
processes, immune function, and high metabolic activity. These processes
were enriched in MNGCs compared to primary ovarian macrophages, suggesting
discrete functionality. MNGCs express CD4 and colocalize with T-cells,
which were enriched in regions of MNGCs, indicative of a close interaction
between these immune cell types. These findings implicate MNGCs in
modulation of the ovarian immune landscape during aging given their high
penetrance and unique molecular signature that supports degradative and
immune functions.