Authors:

Marisa Wen

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About Paper:

Ovarian aging results in a rapid decline in oocyte quality and quantity, contributing to infertility, miscarriage, and broader health consequences such as impaired cardiovascular, musculoskeletal, and immune function. While cellular mechanisms of ovarian aging, such as aneuploidy and mitochondrial dysfunction in oocytes, have been explored, the epigenetic underpinnings of this process remain poorly understood. To bridge this gap, we performed spatial ATAC-seq of mouse ovaries across ages. We identified Fibrillin-1 (FBN-1), a key extracellular matrix gene that modulates tissue elasticity and TGF-f1 signaling, as the top gene with reduced chromatin accessibility in aged murine ovaries. Subsequent RNA in situ hybridization (RNA-ISH) revealed reduced FBN-1 transcript levels in the ovarian stroma and follicle theca layer of reproductively old mice. Western Blot analysis further confirmed the decline in whole ovary total FBN-1 protein levels with age. Immunohistochemistry (IHC) demonstrated that FBN1 is localized throughout the ovarian stroma with a distinct staining pattern in theca-layer. Quantification of IHC staining intensity demonstrated reduced FBN1 levels in ovarian stroma with advanced age. This study highlights FBN1 as a critical gene with reduced accessibility and expression in ovarian aging, and contributes to our understanding of the mechanisms of ovarian functional decline with age. Our ongoing experiments explore elastic fiber organization, comprised of FBN1-based microfibrils and elastin, and the regulation of TGF-f1 fibrosis signaling pathway by FBN1. SOHO SOS HSS SOOSSH HO HOSCOHE SOK OHCHOOOHOSCOS SHE OHOSH ESL ESLEO SPIBDDDIFDFIDIFDTFDIFDDIDHBDFIFGIDFPFDDIFIDIIIDHODIIIIDIDO

Source:

Northwestern University

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Co-authors:

Marisa Wen