# Aging‐Associated Vacuolation of Multi‐Ciliated Cells in the Distal Mouse Oviduct Reflects Unique Cell Identity and Luminal Microenvironment

## TL;DR

Aging causes vacuolated cells in the mouse oviduct's distal end, linked to a unique cell type and reduced blood flow.

## Contribution

Identifies a unique age-related vacuolation phenotype in multi-ciliated cells of the mouse oviduct's INF/AMP region.

## Key findings

- Vacuolated multi-ciliated cells with deformed nuclei appear in aged mouse oviducts.
- INF/AMP epithelium shows unique susceptibility to vacuolation and reduced blood circulation.
- Vacuolation is not hormone-dependent and occurs in hypoxic or hydroxyurea-treated cultures.

## Abstract

The female reproductive organs present with the earliest aging characteristics, such as a decline in fertility and estrous cyclicity. While age‐related changes in the ovary are well documented, it is unclear if any age‐associated changes occur in the other female reproductive organs, such as the oviduct/Fallopian tube. At the distal end of aged oviducts in mice, we found vacuolated multi‐ciliated cells (MCCs) with a severely apically displaced and deformed nucleus. This phenotype was unique to the distal oviduct epithelium—the infundibulum (INF) and ampulla (AMP). Ovariectomy did not affect the timeline of MCC vacuolation, suggesting little involvement of ovulation and hormonal regulation. MCC vacuolation was induced in hypoxia or hydroxyurea treatments in in vitro organotypic culture of all oviduct regions, not limited to the INF/AMP epithelium. This suggests a high oxygen demand in MCCs, compared to other cell types, and a uniquely stressed INF/AMP epithelial microenvironment in vivo. We found that the blood circulation of INF/AMP depended on the ovarian artery, different from the rest of the oviduct epithelium, and its circulation declined along with ovarian activities. We conclude that a decline in local blood circulation and distinct cellular identity of the INF/AMP epithelium caused age‐associated MCC vacuolation, reflecting its mild, chronically stressed microenvironment.

Multi‐ciliated cells in the infundibulum and ampulla (INF/AMP) epithelium are vacuolated in aging. Unique cellular susceptibility of the INF/AMP epithelial population and aging‐associated decline in ovarian artery circulation, which supports the ovary and INF/AMP, contribute to this region‐specific vacuolation phenotype, as a consequence of a mildly stressed microenvironment.