Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece

IntroductionThe male factor is responsible for 50% of infertility cases. Numerous studies have explored the relationship between human sperm morphology assessed via optical and electron microscopy and reproductive outcomes. In the sperm midpiece, mitochondria are arranged in a helical shape, forming...

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Main Authors: María Fernanda Skowronek, Santiago Pietroroia, Gabriel de Cola, Mauricio Ramos, Diego Silvera, Gabriela Casanova, Federico Lecumberry, Adriana Cassina, Rossana Sapiro
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1609081/full
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author María Fernanda Skowronek
Santiago Pietroroia
Gabriel de Cola
Mauricio Ramos
Diego Silvera
Gabriela Casanova
Federico Lecumberry
Adriana Cassina
Adriana Cassina
Rossana Sapiro
Rossana Sapiro
author_facet María Fernanda Skowronek
Santiago Pietroroia
Gabriel de Cola
Mauricio Ramos
Diego Silvera
Gabriela Casanova
Federico Lecumberry
Adriana Cassina
Adriana Cassina
Rossana Sapiro
Rossana Sapiro
author_sort María Fernanda Skowronek
collection DOAJ
description IntroductionThe male factor is responsible for 50% of infertility cases. Numerous studies have explored the relationship between human sperm morphology assessed via optical and electron microscopy and reproductive outcomes. In the sperm midpiece, mitochondria are arranged in a helical shape, forming a compact sheath. Disruptions in this precise mitochondrial structure, size, or organization may contribute to infertility. However, despite established links between abnormal sperm morphology and pathology, mitochondrial abnormalities in sperm remain relatively understudied.MethodsIn this study, we employed computational image analysis and fluorescence labelling to quantitatively assess morphometric changes in the sperm midpiece and correlate these findings with mitochondrial ultrastructure in fertile and infertile men.ResultsOur results revealed a significant increase in midpiece area, width, and roundness in sperm from men with teratozoospermia. These findings were further validated by electron microscopy. The ultrastructural morphometric analysis demonstrated disassembled, enlarged, and irregularly shaped mitochondria in sperm from infertile men. Additionally, we applied ultrastructural morphometric analyses to apoptotic sperm samples, observing similar qualitative and quantitative mitochondrial alterations, particularly in those from infertile individuals.DiscussionTraditional sperm morphology assessments are inherently subjective, but this limitation can be addressed through quantitative morphometric analysis. Enhancing the objectivity and precision of such evaluations is essential for elucidating the biological mechanisms of male infertility and optimizing assisted reproductive technologies. In our study, spermatozoa with poor morphology (<4%) and proximal flagellar abnormalities displayed significantly shorter and wider midpieces. Ultrastructural analysis further revealed that mitochondria in sperm from infertile men were significantly larger and more irregular in shape compared to those from fertile men. These findings indicate an association between altered midpiece morphometry, mitochondrial ultrastructure, and male infertility. The integration of computational tools for automated detection and quantification of these morphological changes offers a promising avenue to improve diagnostic accuracy and deepen our understanding of male reproductive disorders.
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spelling doaj-art-9efe52c1dea249d3ad1a9c280df731dc2025-08-20T02:34:29ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.16090811609081Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpieceMaría Fernanda Skowronek0Santiago Pietroroia1Gabriel de Cola2Mauricio Ramos3Diego Silvera4Gabriela Casanova5Federico Lecumberry6Adriana Cassina7Adriana Cassina8Rossana Sapiro9Rossana Sapiro10Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, UruguayUnidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, UruguayDepartamento de Procesamiento de Señales, Facultad de Ingeniería, Universidad de la República, Montevideo, UruguayDepartamento de Procesamiento de Señales, Facultad de Ingeniería, Universidad de la República, Montevideo, UruguayDepartamento de Procesamiento de Señales, Facultad de Ingeniería, Universidad de la República, Montevideo, UruguayUnidad de Microscopía Electrónica, Facultad de Ciencias, Universidad de la República, Montevideo, UruguayDepartamento de Procesamiento de Señales, Facultad de Ingeniería, Universidad de la República, Montevideo, UruguayDepartamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, UruguayCentro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de la República, Montevideo, UruguayUnidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, UruguayCentro de Investigaciones Biomédicas, Facultad de Medicina, Universidad de la República, Montevideo, UruguayIntroductionThe male factor is responsible for 50% of infertility cases. Numerous studies have explored the relationship between human sperm morphology assessed via optical and electron microscopy and reproductive outcomes. In the sperm midpiece, mitochondria are arranged in a helical shape, forming a compact sheath. Disruptions in this precise mitochondrial structure, size, or organization may contribute to infertility. However, despite established links between abnormal sperm morphology and pathology, mitochondrial abnormalities in sperm remain relatively understudied.MethodsIn this study, we employed computational image analysis and fluorescence labelling to quantitatively assess morphometric changes in the sperm midpiece and correlate these findings with mitochondrial ultrastructure in fertile and infertile men.ResultsOur results revealed a significant increase in midpiece area, width, and roundness in sperm from men with teratozoospermia. These findings were further validated by electron microscopy. The ultrastructural morphometric analysis demonstrated disassembled, enlarged, and irregularly shaped mitochondria in sperm from infertile men. Additionally, we applied ultrastructural morphometric analyses to apoptotic sperm samples, observing similar qualitative and quantitative mitochondrial alterations, particularly in those from infertile individuals.DiscussionTraditional sperm morphology assessments are inherently subjective, but this limitation can be addressed through quantitative morphometric analysis. Enhancing the objectivity and precision of such evaluations is essential for elucidating the biological mechanisms of male infertility and optimizing assisted reproductive technologies. In our study, spermatozoa with poor morphology (<4%) and proximal flagellar abnormalities displayed significantly shorter and wider midpieces. Ultrastructural analysis further revealed that mitochondria in sperm from infertile men were significantly larger and more irregular in shape compared to those from fertile men. These findings indicate an association between altered midpiece morphometry, mitochondrial ultrastructure, and male infertility. The integration of computational tools for automated detection and quantification of these morphological changes offers a promising avenue to improve diagnostic accuracy and deepen our understanding of male reproductive disorders.https://www.frontiersin.org/articles/10.3389/fcell.2025.1609081/fullhuman infertilitysperm midpiecesperm mitochondriafluorescent probeselectron microscopyimage processing
spellingShingle María Fernanda Skowronek
Santiago Pietroroia
Gabriel de Cola
Mauricio Ramos
Diego Silvera
Gabriela Casanova
Federico Lecumberry
Adriana Cassina
Adriana Cassina
Rossana Sapiro
Rossana Sapiro
Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece
Frontiers in Cell and Developmental Biology
human infertility
sperm midpiece
sperm mitochondria
fluorescent probes
electron microscopy
image processing
title Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece
title_full Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece
title_fullStr Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece
title_full_unstemmed Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece
title_short Mitochondrial morphology in fertile and infertile men: image processing and morphometric analysis of the sperm midpiece
title_sort mitochondrial morphology in fertile and infertile men image processing and morphometric analysis of the sperm midpiece
topic human infertility
sperm midpiece
sperm mitochondria
fluorescent probes
electron microscopy
image processing
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1609081/full
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