# Immunohistochemical Detection of Iron-Related Proteins in Sertoli Cell-Only Patterns in Canine Testicular Lesions

## TL;DR

This study explores iron metabolism in Sertoli cell-only tubules in dogs, revealing how iron uptake and cell survival mechanisms vary in different testicular environments.

## Contribution

The study provides new insights into iron-related protein activity and PCNA localization in Sertoli cells under different testicular microenvironments.

## Key findings

- Sertoli cells in SCO tubules retain iron uptake capacity regardless of their surroundings.
- PCNA labeling suggests anti-apoptotic roles in tumor-associated SCO tubules and DNA repair in isolated SCO tubules.
- Iron homeostasis and cell survival mechanisms are linked to testicular tumorigenesis.

## Abstract

Sertoli cell-only (SCO) tubules are a histologic pattern characterized by the absence of germ cells in seminiferous tubules, leaving only Sertoli cells, and are linked to infertility in both humans and dogs. Regarding this syndrome, little is known about its relationship with iron metabolism and proliferation. In this study, we analyzed the immunolabeling of iron-related proteins (Transferrin Receptor 1, Transferrin Receptor 2, and Ferritin Heavy chain 1) and Proliferating Cell Nuclear Antigen (PCNA) in canine SCO tubules under different microenvironments: associated with seminomas, within Sertoli cell tumors, and isolated from tumor cells. Our findings suggest that Sertoli cells in SCO tubules retain their iron uptake capacity regardless of their surroundings, but the utilization of iron for proliferation appears to be limited. Interestingly, the labeling pattern of PCNA hints at a potential non-proliferative role in tumor-associated Sertoli cells. These results provide new insights into the pathophysiology of SCO syndrome and its interaction with testicular tumors.

Sertoli cell-only (SCO) tubules are a histologic pattern characterized by the absence of germ cells within seminiferous tubules, leading to infertility in both humans and dogs. While its association with testicular tumors has been documented, the role of iron metabolism in SCO tubules remains unclear. This study investigates the immunolabeling of key iron-related proteins (Transferrin Receptor 1, Transferrin Receptor 2, and Ferritin Heavy chain 1) and Proliferating Cell Nuclear Antigen (PCNA) in canine SCO tubules within distinct microenvironments: seminomas, Sertoli cell tumors, and isolated. We confirm the presence and distribution of iron-related proteins in Sertoli cells as a part of a Sertoli cell-only pattern across different microenvironments. Our findings suggest a potential increase in iron uptake in association with tumors, and the cytoplasmic PCNA immunolabeling suggests a preferential activation of cell survival rather than proliferation, potentially facilitating neoplastic transformation. In contrast, Sertoli cells in the isolated Sertoli cell-only pattern exhibit nuclear PCNA immunolabeling, possibly correlated to the state of immaturity of Sertoli cells. These findings highlight the role of iron homeostasis and apoptosis in testicular tumorigenesis. Immunohistochemistry revealed that Sertoli cells in SCO tubules actively uptake iron in all conditions, yet their capacity to utilize it for proliferation appears restricted. Interestingly, PCNA labeling exhibits a pattern dependent on the microenvironment: in tumor-associated SCO tubules, it showed cytoplasmic localization, characteristic of an anti-apoptotic function, whereas isolated SCO tubules showed nuclear PCNA labeling, suggesting a potential role in DNA synthesis and repair. These findings highlight the interplay between iron homeostasis and cellular survival mechanisms, offering novel perspectives on its pathophysiology and implications for testicular cancer development.