A1 Refereed original research article in a scientific journal
STAGETOOL, a Novel Automated Approach for Mouse Testis Histological Analysis
Authors: Meikar Oliver, Majoral Daniel, Heikkinen Olli, Valkama Eero, Leskinen Sini, Rebane Ana, Ruusuvuori Pekka, Toppari Jorma, Mäkelä Juho-Antti, Kotaja Noora
Publisher: ENDOCRINE SOC
Publication year: 2023
Journal: Endocrinology
Journal name in source: ENDOCRINOLOGY
Journal acronym: ENDOCRINOLOGY
Article number: bqac202
Volume: 164
Issue: 2
First page : 1
Last page: 13
Number of pages: 13
ISSN: 0013-7227
eISSN: 1945-7170
DOI: https://doi.org/10.1210/endocr/bqac202
Web address : https://doi.org/10.1210/endocr/bqac202
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/178296167
Spermatogenesis is a complex differentiation process that takes place in the seminiferous tubules. A specific organization of spermatogenic cells within the seminiferous epithelium enables a synchronous progress of germ cells at certain steps of differentiation on the spermatogenic pathway. This can be observed in testis cross-sections where seminiferous tubules can be classified into distinct stages of constant cellular composition (12 stages in the mouse). For a detailed analysis of spermatogenesis, these stages have to be individually observed from testis cross-sections. However, the recognition of stages requires special training and expertise. Furthermore, the manual scoring is laborious considering the high number of tubule cross-sections that have to be analyzed. To facilitate the analysis of spermatogenesis, we have developed a convolutional deep neural network-based approach named "STAGETOOL." STAGETOOL analyses histological images of 4 ',6-diamidine-2 '-phenylindole dihydrochloride (DAPI)-stained mouse testis cross-sections at x400 magnification, and very accurately classifies tubule cross-sections into 5 stage classes and cells into 9 categories. STAGETOOL classification accuracy for stage classes of seminiferous tubules of a whole-testis cross-section is 99.1%. For cellular level analysis the F1 score for 9 seminiferous epithelial cell types ranges from 0.80 to 0.98. Furthermore, we show that STAGETOOL can be applied for the analysis of knockout mouse models with spermatogenic defects, as well as for automated profiling of protein expression patterns. STAGETOOL is the first fluorescent labeling-based automated method for mouse testis histological analysis that enables both stage and cell-type recognition. While STAGETOOL qualitatively parallels an experienced human histologist, it outperforms humans time-wise, therefore representing a major advancement in male reproductive biology research.
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