Abstract
Homeostasis of the oviductal infundibulum epithelium is continuously regulated by signaling pathways under physiological and pathological conditions. Herein, we investigated the expression of hedgehog (Hh) signaling–related components in the murine oviductal infundibulum, which is known to maintain homeostasis in the adult epithelium. Additionally, using autoimmune disease-prone MRL/MpJ-Faslpr/lpr (MRL/lpr) mice showing abnormal morphofunction of the ciliated epithelium of the infundibulum related to the oviductal inflammation, we examined the relationship between Hh signaling and pathology of the infundibulum. The expression and localization of Pax8, a marker for progenitor cells in the oviductal epithelium, and Foxj1, a marker for ciliogenesis, were examined in the infundibulum. The results showed that Pax8 was downregulated and Foxj1 was upregulated with aging, suggesting that homeostasis of the infundibulum epithelium of MRL/lpr mice was disturbed at 6 months of age. In all mice, the motile cilia of ciliated epithelial cells in the infundibulum harbored Hh signaling pathway-related molecules: patched (Ptch), smoothened (Smo), and epithelial cells harbor Gli. In contrast, Ptch, Smo, and Gli2 were significantly downregulated in the infundibulum of MRL/lpr mice at 6 months of age. The expression levels of Pax8 and Foxj1 were significantly positively correlated with those of Ptch1, Smo, and Gli2. Hh signaling is thought to be involved in homeostasis of the ciliated epithelium in the infundibulum. In MRL/lpr mice, which show exacerbated severe systemic autoimmune abnormalities, molecular alterations in Hh signaling-related components are considered to interact with local inflammation in the infundibulum, leading to disturbances in epithelial homeostasis and reproductive function.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Funding
This work was supported in part by the JSPS KAKENHI Grant (No. 19K23708 and 21K05976), Rakuno Gakuen University Research Fund (No. 2020–01), Suhara Memorial Foundation Research Grants, and Uehara Memorial Foundation Research Incentives Grants (M. H.).
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Conceptualization: M.H. and O.I.; methodology: M.H., O.I., Ta.N., M.A.M, Te.N., and Y. H.; validation: M.H., O.I., and T.N.; formal analysis: M.H. and O.I.; investigation: M.H., O.I., Ta.N., and M.A.M.; resources: M.H., O.I., and M.A.M.; data curation: M.H.; writing — original draft: M.H. and O.I.; writing — review and editing: M.H., O.I., T.W., and Y.K.; visualization: M.H. and O.I.; supervision: M.H. and Y.K.; project administration: O.I. and YK; funding acquisition: M.H.
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Animal experimentation was approved by the School of Veterinary Medicine, Rakuno Gakuen University (approval no. VH19A6). Animals were handled in accordance with the Guide for the Care and Use of Laboratory Animals, Rakuno Gakuen University, Japan.
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Hosotani, M., Ichii, O., Namba, T. et al. Expression of Indian hedgehog signaling in murine oviductal infundibulum and its relationship with epithelial homeostasis. Cell Tissue Res 391, 595–609 (2023). https://doi.org/10.1007/s00441-022-03722-w
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DOI: https://doi.org/10.1007/s00441-022-03722-w