Mechanosensitive Piezo1 channel is highly expressed in the age-induced fibrotic uterus

As the trend of delayed childbearing continues, uterine aging is increasingly recognized as a critical factor impacting reproductive health and contributing to infertility. However, the underlying mechanisms of uterine aging remain poorly understood.

This study aims to explore age-related changes in the extracellular matrix (ECM) and the involvement of Piezo1, a mechanically sensitive non-selective cation channel, in mediating Wnt/β-catenin signaling within the aging uterus of rats.

Eighteen female rats were divided into three age groups: 3 months (n = 9), 9 months (n = 9), and 18 months (n = 9). We performed comparative analyses of Piezo1 expression and fibrosis-related gene expression through immunohistochemical staining. Morphological changes in the uterine tissue were observed using Hematoxylin and Eosin (H&E) and Masson staining techniques.

Our findings revealed significant morphological and molecular alterations in the uterine tissue of aging rats. The endometrium became thinner, glandular structures decreased, and fibrotic deposits were evident with advancing age. Additionally, aging was associated with reduced endometrial cell proliferation. ECM-related genes, including PAI, CTGF, Fn, α-SMA, TGFβR, MMP9, MMP13, and CDH1, were upregulated in the 18-month-old group compared to the 3-month-old group. Furthermore, an increased abundance of Piezo1 protein and activation of the Wnt/β-catenin signaling pathway were observed in fibrotic uterine tissues of aged rats.

In conclusion, our study identifies uterine fibrosis as a key feature of age-related changes in the rat uterus, with Piezo1 highly expressed in fibrotic uterus and may potentially playing a crucial role in this process by activating the Wnt/β-catenin pathway. These findings provide new insights into the molecular mechanisms of uterine aging, with potential implications for addressing age-related infertility.